Résumé

Le dromadaire (Camelus dromedarius), qui est un mammifère bien adapté au désert est une espèce à reproduction saisonnière. Sa saison sexuelle a lieu durant l’hiver et le printemps. Ces périodes coïncident avec l’abondance des ressources alimentaires et des conditions climatiques favorables pour la survie de la progéniture. Toutefois les mécanismes impliqués dans le contrôle de cette saisonnalité restent encore mal élucidés. L’objectif de cette revue est de décrire les caractéristiques de la reproduction chez le dromadaire. Cela inclue la distribution géographique de sa saison sexuelle et son déclenchement possible par plusieurs paramètres environnementaux physiques, notamment la température ambiante, la photopériode et la quantité de précipitations. De plus, plusieurs aspects de cette saisonnalité ont été discutés chez le mâle et la femelle. Finalement, cette revue analyse les facteurs neuroendocriniens impliqués dans la saisonnalité de reproduction, notamment, le rôle putatif de deux neuropeptides hypothalamiques, le kisspeptin et le (Arg) (Phe) peptide apparenté.


Mots-clés: Dromadaire, saisonnalité de reproduction, précipitations, photopériode, température ambiante, disponibilité alimentaire, kisspeptin, RFRP.

INTRODUCTION

All living organisms have to adapt their physiological processes to the daily and seasonal environmental changes of their biotopes. Various functions such migration, hibernation, molting, diapause and reproduction are adjusted to occur in an adequate period of the year. Notably, a tight timing of reproduction is crucial for optimizing birthing and survival of the offspring. This control involves the effect of genetic, metabolic and environmental factors. Seasonal breeding species are grouped into “long day” and “short day” breeders depending on time of the year when mating activity occurs. “Long day” breeders become sexually active when day length gets longer (spring-summer); while in “short day” breeders this activity arises when day length goes shorter. Furthermore, reproductive capacity depends on climatic conditions. Thus, animals living under harsh environmental conditions must cope with their biotopes and need to better synchronize their reproductive activity.

The dromedary camel is a well-adapted desert mammal. It displays a large distribution including three continents within a latitudinal zone laying between 40°N to 40°S (Figure 1). The distribution area is mainly confined to the semi-arid and arid regions of Africa and Asia. More than 80% of the world camel’s population is found in Africa particularly North Africa, Sahel and the Horn of Africa. In Asia, a regular camel population is found in India and Pakistan, in addition to Arabian countries. Finally, an important population of camel is also found in Australia. This species exhibit a seasonal reproduction with mating-induced ovulation. Its breeding season is relatively short and the gestation period lasts 13 months. This period may be affected by the date of conception (Elias et al., 1991) food availability (Yagil and Etzion, 1984). Therefore, mating and parturition are occurring at the same period of the year which depends on camel’s geographical distribution. In most cases, the matting period occurs during the rainfall period associated with low ambient temperatures and good food availability. Several studies have been carried out in different Asian and African countries to define the breeding season in the camel and the environmental factors which may determine its onset and its end. Photoperiod, ambient temperature and rainfall with subsequent food availability seem to be the three major abiotic factors that have been considered to be involved in this seasonality. The exact role of each of these abiotic factors in the control of reproduction seasonality in camels requires a thorough analysis.

Understanding the mechanisms through which rhythmic changes of environmental factors restrain camel’s breeding activity to a definite period of the year is critical for advancing knowledge of reproductive physiology and breeding management. In most seasonal mammals, the annual changes in the nocturnal production of melatonin is pivotal to drive seasonal breeding. Recent studies have provided evidences that melatonin is involved in the regulation of two populations (kisspeptin (Kp) or (Arg)(Phe)-related peptide (RFRP)) of hypothalamic neuropeptides involved in the control of GnRH neuronal activity and the downstream pituitary-gonadal axis (Clarkson and Herbison, 2006; Irwig et al., 2004; Kriegsfeld et al., 2006; Rizwan et al., 2012).

The objective of the present review is to provide a new and thorough look at camel reproductive seasonality, firstly through reviewing the role of abiotic factors in the control of seasonal breeding in camels distributed within 16 geographical zones (latitudinal distribution between 33°N to 40°S) and secondly by investigating how the different environmental cues impact on the neuroendocrine control of seasonal breeding with a special focus on the putative role of Kp and RFRP neurons.

BEHAVIOR, GONADAL AND HORMONAL CHANGES DURING THE CAMEL’S BREEDING CYCLES

In male, the breeding season is characterized by several changes in sexual behavior including aggressiveness, exteriorization of the soft palate, urine spraying and smudging of poll gland secretions (Tibary and Anouassi, 1997). During this period, the testes and accessory glands show large increase in size, weight and activity (Abdel-Raouf et al., 1975; Sigh and Bharadwaj, 1978; Yagil and Etzion, 1980). The seminiferous tubule’s diameter becomes larger during the breeding season (Abdel-Raouf et al., 1975). The accessory gland weight increase in parallel with the testis indicating that their activity is regulated by androgens (Mahmoud, 2006). Recently, S-100 and alpha smooth muscle actin, two biologically active proteins of the epididymis, have been reported to exhibit seasonal changes with a higher expression at the breeding season (Ibrahim et al., 2016).

Although spermatogenesis and male hormone (testosterone and progesterone) secretion occur continuously throughout the year, both are higher during the breeding season (Tingari et al., 1984, Abdel-Raouf et al., 1975; Zia-ur-Rahman et al., 2007; Bedrak et al., 1983; El-Harairy and Attia, 2010). The seasonal regulation of androgen secretion is linked to changes in pituitary activity since luteinizing hormone (LH) secretion shows higher frequency and amplitude during rutting (Marie, 1987) while FSH levels are higher when ambient temperature is low (Fat-Halla and Ismail, 1980). In addition, serum prolactin levels are also higher during the non-breeding season and decrease significantly in the rutting season (Ismail et al., 1984; Azouz et al., 1992).

In female camel, a number of behavioral changes are observed during the breeding season such as frequent urination, vulvae discharge, vulvae swelling, male seeking, bleating, foul vulval odor, tail raising, inappetence and mounting behavior (Tibary and Anouassi, 1997; Abdussamad et al., 2011). Female dromedaries are seasonal polyestrous animals with a sustained ovarian follicular cycle in the breading season until fecundation. In the non-breading season, ovarian activity decreases down to a limited number of small follicles (Sghiri and Driancourt, 1999).

Estradiol levels follow the ovarian activity with higher cycling levels in the breeding season and low levels during the non-breeding season (Elias et al., 1984; Ali et al., 2007). In correlation with the ovaries, pituitary activity attested by LH secretion, is lower in summer than in winter (Khaldoun, 1990). Furthermore, pituitary’s sensitivity to GnRH is increased during the rutting season, with a larger release of LH (Bono et al., 1989).

TIMING OF THE BREEDING SEASON AROUND THE WORLD

Because camel reproductive activity strongly depends on environmental factors, the timing of their breeding varies according to geographical location (Table 1).

Analysis of camel’s breeding seasons in 16 zoogeographical zones distributed from latitude 33°N to 40°S, may help understanding the involvement of photoperiod, ambient temperature and rainfall with subsequent food availability in the triggering of breeding activity (Figures 2 and 3).

At high latitude (from 33°N to 23°N), in Algeria, Egypt, India, Israel, Morocco, Oman, Pakistan, Saudi Arabia, Tunisia, and UAE, the breeding season occurs under short photoperiod associated with rainfall and low ambient temperatures.

In Mali (latitude 16°N), the breeding season takes place during the short days but its onset occurs earlier after the summer solstice. This may be related to the abundance of rainfall and thus good food availability at this period.

More towards the south, in Nigeria (latitude 12°N) the breeding season is limited to short days whereas in Sudan (latitude 14°N) it extends to several months in long days. In these geographical zones, temperature and photoperiod profiles are similar and the rainfall occurs at the same period although the amount of rainfall is usually higher in Nigeria (240 mm) than in Sudan (110 mm). The climatic conditions are more drastic in Sudan and therefore camel’s reproductive cycle is well synchronized to the rainfall period. A prediction of this rainfall period triggers the reproductive activity to start early than in Nigeria and to extend the breeding season beyond the precipitation period. In Nigeria, the precipitation rate during a single period of the year maintains food availability during the following months, and thus the breeding season is rather driven by short photoperiod and low ambient temperatures that rainfall as in the case in zones of high latitudes.

In Somalia (latitude 3°N), ambient temperature and photoperiod are nearly constant throughout the year but precipitations occur at two seasons. The two breeding seasons in this area correspond to the two rainy seasons because of food abundance.

In Kenya (latitude 0°), photoperiod, ambient temperature are constant and precipitation occurs almost all the months and consequently, food availability and climatic conditions are quite stable throughout the year. Therefore, although camels are able to integrate environmental changes, seasonal reproduction is not required and camel can breed at any period of the year. In fact, very small changes in the environment can be perceived by animals. As an example, it was demonstrated that the Arvicanthis niloticus a small tropical rodent is able to integrate minimal annual variations of photoperiod which can arrive at 45 min of differences (Sicard et al., 1992).

In Australia (latitude 23 °S) camel’s breeding season also occur under short photoperiod and low ambient temperatures, and therefore its timing shows a six-months out of phase when compared to that in northern hemisphere. Photoperiod and temperature appear the most relevant cues since rainfall occurs with a low rate throughout the year.

As a general rule, the breeding season in the dromedary camel living at high latitudes of both northern and southern hemispheres occurs when the photoperiod is short and the temperature is low associated to some precipitations. Therefore, their reproductive cycle is in opposite phase relationship between the both hemispheres, as for other mammals like ewes in which the breeding season starts when day length decreases (end of summer/beginning of autumn) in the northern hemisphere, and when day length increases in the southern hemisphere (for review see Lofts, 1975; Vivien-Roels and Pévet, 1983). At high latitudes, annual cycles of photoperiod and probably ambient temperature are strong enough to synchronize reproductive activity to rainfall and good food availability period. However, when climatic conditions are drastic with limited rainfall, the breeding season tends to start earlier during long days or may also appears twice a year to match precisely the two rainfall seasons. There is no need to compare rainfall and food availability to photoperiod and ambient temperature, since the later are proximate factors while the former are ultimate factors (Lofts, 1975; Gwinner, 1981). An interesting case is observed in Sudan where the breeding season starts earlier than the rainfall season indicating the existence of a predictive adaptation. In the equatorial area also, camel can breed throughout the year as rainfall and good food availability are quite stable all along the year.

INVOLVEMENT OF FOOD AVAILABILITY,  AMBIENT TEMPERATURE AND PHOTOPERIOD CYCLES IN THE ONSET OF CAMEL BREEDING SEASON

Several studies have been conducted on the behavioral and hormonal control of reproduction in the dromedary camel. However, only a few works have investigated the effect of environmental factors on their breeding seasonality.

Food availability and energy balance

Energy given by food intake is used for different metabolic processes or stored as glycogen or lipids in the body. Basic metabolism, necessary for homeostasis, should be first satisfied, while other functions of high energetic cost, such as growth and reproduction, can be satisfied later on in the case of negative energy balance (Bronson, 2009). Indeed, food availability is the ultimate factor for the survival of the offspring (Lofts, 1975; Gwinner, 1981).

As stated above, breeding activity in the camel is usually synchronized with the rainfall periods so that birth of offspring occurs during a good grazing period. It seems that rainfall cue can partially or totally override the effect of photoperiod (Musa et al., 1993; Mukasa-Mugerwa, 1981). Indeed, in the United Arab Emirates, it was reported that well-fed and watered female camels maintain their ovarian activity throughout the year and that the seasonal aspect of the breeding in this species was rather linked to the increased embryonic loss and decreased libido of males during summer season (Tibary and Anouassi, 1997). It has been also demonstrated, that rainfall season can affect ovarian activity and gonadotropin secretion, with higher GnRH responsiveness, LH and sex steroid secretion during this season (Bono et al., 1989; Bono et al., 1988). However, these changes cannot be attributed to a direct effect of precipitation, but possibly to a synergism with photoperiod and ambient temperature since all these cues show seasonal variations. Because photoperiod and ambient temperature show the most predictable annual changes, camels probably use these cues to predict the suitable climate for breeding. At our knowledge, there are no controlled experimental designs that permits discriminating an unique effect of one single environmental factor in camels. In the equatorial countries, such as Kenya, there is sufficient food available all along the year and therefore camel breed at any time of the year.

An equilibrated body energy balance, reached when the amount of food intake is sufficient to counteract energy cost, is crucial to sustain reproductive activity. In most female mammal, including farm animals, food restriction is known to impede ovarian activity (Comin et al 2002; Li et al., 2014) Thus, in food restricted mice, ovulation is abolished until they can increase their food intake, even if they are kept at low temperatures (Manning et Bronson, 1990). Similarly, it has been shown that low circulating level of glucose or metabolic inhibition reduces GnRH neurons activity (Zhang et al., 2007).

In order to elucidate how metabolic cues control of reproduction, several studies focused on kisspeptin (Kp), a hypothalamic peptide essential for puberty onset and normal reproduction (De Roux et al., 2003; Seminara et al., 2003). Kp is a product of the Kiss1 gene expressed in neurons of the arcuate nuclei or in more rostral areas around the third ventricle (anteroventral paraventricular nucleus in rodents, or preoptic area in larger mammals). Kp is an extremely potent stimulator of GnRH neuronal activity and consequently gonadotropin secretion (Clarke et al., 2008). There is evidence of a relationship between the metabolic status and kisspeptin expression. For example, fasting in rat induces a decrease in Kp expression associated with an increase in its G protein-coupled receptor Kiss1R (Castellano et al., 2005). In line with this, Kp neurons in the arcuate nucleus express the receptor for leptin, an anorexigenic hormone produced by fatty tissues (Margetic et al., 2002). Additionally, administration of this hormone to leptin knock-out mice restores Kp expression to a level comparable to that observed in the wild type animals (Smith et al., 2006). Other metabolic modulators, like ghrelin, proopiomelanocortin (POMC) and neuropeptide Y (NPY) are possible regulators of Kp neurons (De Bond and Smith, 2014). These observations suggest that Kp neurons may be able to adjust the activity of the gonadotropic axis according to the metabolic state of the body (De Bond and Smith, 2014; Garcia-Garcia, 2012).

Effect of ambient temperature on breeding activity

Arid and semi-arid areas display variations in photoperiod but also exhibit high fluctuations of ambient temperature. In mammals, extreme temperatures can induce irregularities in sexual activity like delayed puberty, delayed onset of breeding season, irregular cycle duration and frequent anovulatory estrus (Hafez, 1964). In sheep, the strongest regulator of seasonal breeding is photoperiod but ambient temperature may also modulate this activity (Rosa et Bryant, 2003). Ewes are short day breeder at high latitudes and long day breeder at low latitude, but it was reported that when ewes from northern hemisphere were put under low ambient temperatures during the summer, their reproductive season began earlier than those kept under normal temperatures (Dutt and Bush, 1955; Godley et al., 1966). In goats, heat stress induces a decrease of ovary LH receptor and responsiveness to LH pulses, a decrease in follicular steroidogenic activity attested by a reduction in oestradiol synthesis and a delay in recruitment of the ovulatory follicle (Kanai et al., 1995; Ozawa et al., 2005). In mares, high temperature was associated with disturbance of the estrous cycle, development of anovulatory hemorrhagic follicles and increased early embryo loss. In cattle, high ambient temperature and humidity (heat index) affect not only steroidogenesis but also quality of oocytes and results in poor fertility and increased pregnancy loss (Ana Yasha et al., 2017; Hansen, 2009).

One of the pineal hormones, 5-methoxytryptophol (5ML) was proposed to act as mediator for the effect of ambient temperature on reproduction. Indeed, as reviewed by Vivien-Roels and Pévet (1983), ambient temperature affects pineal gland activity in different vertebrates including mammals. In the jerboa, 5ML levels are lower during the breeding seasons (spring) and injection of this pineal hormone induces a decrease in testicular volume (Bouhaddou, 2016). In the dromedary camel, except the losing weight effect (up to 30%) observed in males during the breeding period (Anouassi and Tibary, clinical observations), there is no report evoking a direct effect of ambient temperature on its reproductive activity. However, a recent study performed in our laboratory has reported that in the camel the ambient temperature cycles drive melatonin rhythm as does photoperiod (El Allali et al., 2013). This indicates that a thermo-period related to the annual cycles of ambient temperature can also synchronize the breeding season in camel.

Control of seasonal breeding by photoperiod

Photoperiod is the major environmental factor synchronizing seasonal reproduction as reviewed in several species (Reiter, 1978; 1981; 1974; Hoffman, 1979; Lincoln, 1979; 1992; Lincoln and Short, 1980; Lincoln and Richardson, 1998; Lincoln et al., 2001). Artificial modification of the photoperiod (lighting conditions) is used to advance the breeding season in goat and sheep (Malpaux et al., 1999) and horses (Murphy et al., 2014).

Animals are informed about annual variations in photoperiod through changes in the duration of the melatonin nocturnal peak (Bartness et al., 1993; Goldman, 2001). Melatonin synthesis and release from the pineal gland depend on a neuronal pathway involving a retino-hypothalamic tract connecting the retina to the hypothalamic suprachiasmatic nuclei which host the master circadian clock and downstream the hypothalamic paraventricular nuclei, the intermediolateral cell column of spinal cord and the superior cervical ganglia which noradrenergic neurons project to the pineal gland (Larsen et al., 1998; Teclemariam-Mesbah et al., 1999). The release of norepinephrine occurs at night only under the control of the circadian clock synchronized by the light/dark cycle perceived by the retina (Drijfhout et al., 1996). Norepinephrine displays a potent stimulatory effect on melatonin synthesis (King and Steinlechner, 1985; Stehle et al., 2001). Therefore, circulating melatonin is about 10 times higher during the night and the duration of the nocturnal melatonin peak is proportional to the duration of the night (Illnerova et al., 1984; Arendt, 1986; Reiter, 1986; Pévet et al., 1991; Reitter, 1993; Tast et al., 2001).

Like other mammals, the dromedary camel shows daily (Vyas et al., 1997) and seasonal (El Allali et al., 2005) rhythms in melatonin. Indeed, this species, integrates photoperiodic changes under various latitudes through changes in the duration of the nocturnal melatonin peak (Figure 4). Therefore, camels may use the photoperiodic change in melatonin synthesis to synchronize their breeding season.

Recent research findings are in favor of a melatonin effect on the breeding season in the camel. An early experiment carried out by Vyas et al., (2008) revealed that application of a short photoperiod treatment by protecting the eyes from the solar lights stimulates the ovarian activity in sexually quiescent female camels. Later, Dholpuria et al., (2012) showed that during the breeding season, melatonin implant improved fertility by increasing follicular growth. Similarly, in a recent study we observed that exogenous melatonin given during the seasonal anestrus period increased the ovarian activity of 6 camels as compared to a control group (El Allali, unpublished data). In male camels, melatonin implants can improve reproductive performance during the non-breeding season by increasing libido and testosterone levels in the treated camels as compared to the controls (Swelum et al., 2016)

In all seasonal mammals studied so far, photoperiodic variations of the nocturnal peak of melatonin synchronize reproduction activity with the season. In several species, exogenous melatonin was used to control the season of breeding and increase fertility and prolificacy (Bartness et al., 1993; Misztal et al., 2002). Melatonin acts via its specific receptors MT1 (Mel1a), MT2 (Mel1b) which are expressed in multiple tissues through the body (Dufourny et al., 2008; Reppert et al., 1996) with the highest concentration of MT1 observed in the pars tuberalis (PT) of numerous species (Vanĕcek et al., 1987; Weaver et al., 1989; Williams et al., 1989).

PT integration of melatonin signal via the MT1 receptors results in the regulation of thyroid-stimulating hormone (TSH) synthesis with at much higher levels in long photoperiod as compared to short photoperiod (Dardente et al., 2012). TSH then activates tanycytes TSH receptor to increase thyroid hormone (T3) levels in the mediobasal hypothalamus via a dual activation of deiodinases 2 and inhibition of deiodinases 3 (Dardente, 2012; Hanon et al., 2010; Klosen et al., 2013; Nakao et al., 2008). Recently, Klosen et al., (2013) have shown that chronic administration of TSH to sexually inhibited short photoperiod adapted Siberian and Syrian male hamsters, restores a long day reproductive phenotype. In parallel, TSH could increase the expression of two neuropeptides recently described to be involved, in the control of seasonal breeding, the hypothalamic RFRP and Kp peptides (Revel et al., 2006; Ancel et al., 2012). These results lead to the hypothesis that the control of seasonal breeding by the melatonin-TSH-T3 occurs via these neurons (Klosen et al., 2013; Dardente et al., 2016) (Figure 5).

Figure 5: Schematic illustration showing how melatonin controls the seasonal breeding. By acting on the pars tuberalis, low levels of melatonin during long days allows high thyroid stimulating hormone (TSH) production, which increases deiodinase 2 (Dio2) expression in the tanycytes lining the 3rd ventricle leading to a local increase of T3 production. T3 is thought to increase the synthesis of kisspeptin (KISS) and (ARG)(PHE)related peptide (RFRP), two neuropeptides involved in the regulation GnRH neurons and the downstream secretion of two pituitary hormones, LH and FSH , that regulate gonad activity (modified from Klosen et al., 2013)

KISSPEPTIN SYSTEM AND SEASONAL REPRODUCTION

The Kiss1 gene was first discovered in 1996 as an inhibitor of human melanoma metastatic potential (Lee et al., 1996). The Kiss1 gene is translated into a long propeptide of 145 amino acids (aa) which is further cleaved into shorter peptides with sequences varying from 10 to 54 aa (Kotani et al., 2001; Ohtaki et al., 2001). All Kp isoforms contain the minimal 10 aa N-terminal active sequence allowing their binding to the 7 transmembrane domains G protein coupled receptor, Kiss1R (previously named GPR54) (Kotani et al., 2001; Muir et al., 2001; Ohtaki et al., 2001). Kiss1R are highly expressed on GnRH neurons and their activation is responsible for the stimulation the reproductive axis (Clarkson and Herbison, 2006).

In several mammalian species, a cluster of Kp neurons is found in the arcuate nucleus (ARC) (Rat, Irwig et al., 2004; Desroziers et al., 2010; Sheep, Estrada et al., 2006; Goodman et al., 2007; Hamster, Revel et al., 2006; Mason et al., 2007; Mouse, Clarkson et Herbison, 2006; Primates, Rometo et al., 2007; Ramaswamy et al., 2008; Hrabovszky et al., 2010; Equine, Decourt et al., 2008 Magee et al., 2009). In addition, Kp neurons are identified in the pre-optic region in human, monkey, sheep, and rodents. In rodent, these neurons are located in the anteroventral periventricular nucleus (AVPV) and extend to the periventricular nucleus (PeN) (Gottsch et al., 2004; Smith et al., 2005); whereas in sheep, monkey and man, they extend rostro-caudally to reach the pre-optic area (POA) (Lehman et al., 2014). Notably, these two neuronal populations exhibit sexual dimorphism in most of the species studied to date. In sheep and human, ARC and POA Kp are more numerous in females than in males (Cheng et al., 2010; Hrabovszky et al., 2010); whereas in rodents only the AVPV shows higher Kp neurons in females than in males (Clarkson and Herbison, 2006; Kauffman et al., 2007).

Revel et al., (2006) demonstrated in Syrian hamsters that the Kiss1 gene expression is inhibited by melatonin in short photoperiod, and that this melatonin-driven expression of Kiss1 plays a pivotal role in the seasonal control of the gonadotropic axis. Further studies in sheep also reported strong photoperiodic variation of Kiss1 expression (Wagner et al., 2008; Smith et al., 2007; Chalivoix et al., 2010; Figure 6). Importantly Kiss1 expression is strongly regulated by sex steroid feedback but this effect is opposite in the ARC (inhibition of Kiss1 expression) and AVPV/POA (stimulation of Kiss1 expression) (Smith et al., 2005; Ansel et al., 2010). There is an opposite regulation of the ARC Kiss1 gene, with higher levels during short photoperiod in sheep and during long photoperiod in Syrian hamster, in conjunction with seasonal reproductive activity. Photoperiod also affects the density of Kp fibers projections onto GnRH neurons (Smith et al., 2008).

Figure 6: Photoperiod effect on Kiss-1 expression in the sheep arcuate nuclei (Wagner et al., 2008)

In both hamster (Revel et al., 2006) and ewe (Caraty et al., 2010), chronic administration of Kp to sexually inactive animals restores gonadal activity to the level observed during the breeding season. This demonstrates that seasonal regulation of Kp is pivotal to synchronization of reproduction with seasons. In camel, preliminary results in our laboratory (Ainani, El Bousmaki, Achaâban, Ouassat, Piro, Simonneaux and El Allali, unpublished data) show that Kp is expressed in neurons in the various hypothalamic nuclei. Further studies are needed to establish whether this neuropeptide may be involved in camel seasonal breeding (Figure 7).

RFRP SYSTEM AND SEASONAL REPRODUCTION

RFRP peptides are hypothalamic peptides belonging to the same RFamide peptide family as does Kp. A homologous peptide called gonadotrophin inhibitory hormone (GnIH) has first been discovered in the quail to inhibit GnRH-induced LH release by the pituitary (Hinuma et al., 2000). In mammals, the orthologous gene is called Rfrp and encodes three peptides RFRP-1,-2 and 3 peptides. Only RFRP-1 and RFRP-3 are found in rodents (Fukusumi et al., 2001; Ukena et al., 2002). In all species investigated thus far, the RFRP neurons are located in an area between DMH and VMH (Hinuma et al., 2000; Revel et al., 2008; Clarke et al., 2008; Dardente et al., 2008; Henningsen et al., 2016) (Figure 8).

As Kp neurons, RFRP neurons display a marked photoperiodic variation. However, unlike Kp, this photoperiodic variation is driven by melatonin only. It is not controlled by sex steroid feedback and is inhibited during the short photoperiod in all seasonal species investigated (Revel et al., 2008; Dardente et al., 2008; Clarke et al., 2008; Ancel et al., 2012; Ubuka et al., 2012; Janati et al., 2013; Talbi et al., 2016; Henningsen et al., 2016) (Figure 8). In the Syrian hamster, the number of RFRP neurons is higher in females than in males (Henningsen et al., 2016; Figure 8).

Although RFRP has often been reported to modulate GnRH neuronal activity and gonadotropin production, this effect is variable depending on species, environmental photoperiod and sex.

In rats, mice and sheep, it inhibits GnRH neurons and gonadotropin release (Clarke et al., 2008; Anderson et al., 2009; Ducret et al., 2009; Johnson et al., 2007; Pineda et al., 2010). In contrast, in the male Syrian hamster, it displays a stimulatory effect on the hypothalamo-pituitary gonadal axis. A chronic administration of RFRP-3 in sexually inactive short day-adapted hamsters fully restore a long day, sexually active phenotype (Ancel et al., 2012). In the male Siberian hamster, the effect of RFRP-3 depends on the photoperiodic regimen, being stimulatory in short day- and inhibitory in long day-adapted hamsters (Ubuka et al., 2012).

Finally, in female Syrian hamsters, in contrast to males, an acute injection of RFRP-3 at the time of the preovulatory LH surge reduces the amount of LH produced (Henningsen et al., 2016). All together, these observations indicate that, although melatonin inhibition of RFRP expression during short day is well conserved among seasonal species, its effect on reproductive activity varies depending on species, environmental photoperiod and sex.

In camels, preliminary results from our laboratory (Ainani, El Bousmaki, Achaâban, Ouassat, Piro, Simonneaux and El Allali, unpublished data) show that neurons expressing RFRP-3 are found in the dorsomedial hypothalamus (Figure 9). Studies are underway to investigate whether this peptide display seasonal variations and whether it can be involved in camel’s seasonal breeding.

Figure 9: Immunofluorescent labeling of RFRP neurons in the dorsomedial nuclei (DMH) of female camel

CONCLUSION

Food availability for the offspring survival is presumed to be the ultimate factor that determines the breeding season (Lofts, 1975; Gwinner, 1981). Photoperiod and to a less extent ambient temperature and rainfall are considered as proximate factors serving for the prediction of the best timing of good food availability and thus for controlling the breeding season. In camels raised at high latitude, photoperiod and probably ambient temperature are the main factors controlling the breeding season which occurs when photoperiod is short and ambient temperature is low. Mechanisms involved in the control of seasonality by photoperiod are relatively well elucidated. However, there is less evidence how food availability and rainfall can give a direct signal to the brain to modulate the anticipatory response allowing a prediction of breeding seasons.

In harsh environmental conditions, rainfall may become a strong proximate factor, and in these conditions, the camel may display breeding seasons synchronized to rainfall periods.

Photoperiod is a major environmental factor which controls seasonal reproduction via the annual change in nocturnal melatonin secretion. Recent data have pointed to melatonin acting through the regulation of reproductive neuropeptides Kp and RFRP via a TSH secretion from the pars tuberalis. Preliminary results in our laboratory show that melatonin injection improves camel reproductive capacity and that Kp and RFRP neurons are present in the camel hypothalamus. Further studies are in progress to investigate how these RF-amide peptides are regulated by proximate environmental factors and whether they are involved in the control of camel reproductive seasonality.

REFERENCES 

Abbas B., Chabeuf N., Saint-Martin G., Bonnet P., Millaird A., Beshir H., Musa B.E. (1992). Camel Pastoralism in the Butana and Northeastern Sudan: an interdisciplinary study. Nomadic Peoples, 31: pp. 64-84.

Abdel-Raouf M., El-Bab M.R., Owaida M.M. (1975). Studies on reproduction in the camel (Camelus dromedarius) V. morphology of the testis in relation to age and season. J. Reprod. Fertil., 43: 109-116.

Abdoon A.S. (2001). Factors affecting follicular population, oocyte yield and quality in camels (Camelus dromedarius) ovary with special reference to maturation time in vitro. Anim. Reprod. Sci., 66: 71-79.

Abdussamad A.M., Holtz W., Gauly M., Suleiman M.S., Bello M.B. (2011). Reproduction and breeding in dromedary camels: insights from pastoralists in some selected villages of the Nigeria-Niger corridor. Livestock Research for Rural Development. 23(8).

Ali S., Ahmad N., Akhtar N., Rahman Z., Sarwar M. (2007). Effect of season and age on the ovarian size and activity of one-humped camel (Camelus dromedarius). Asian-Australas. J. Anim. Sci. 20: 1361-1366.

Al-Qarawi A., Abdel-Rahman H., El-Belely M., El-Mougy S. (2001). Intratesticular morphometric, cellular and endocrine changes around the pubertal period in dromedary camels. Vet. J. 162: 241-249.

Ana Yasha F..S., Luanna Figueirêdo Batista., Bonifácio Benicio de Souza., Aline Ferreira da Silva., Érico Luiz de Barros Correia. (2017). J. Anim. Behav. Biometeorol., 5:7-12.

Ancel C., Bentsen A.H., Sébert M.E., Tena-Sempere M., Mikkelsen J.D., Simonneaux V. (2012). Stimulatory effect of RFRP-3 on the gonadotrophic axis in the male Syrian hamster: the exception proves the rule. Endocrinology, 153: 1352-1363.

Anderson G.M., Relf H.L., Rizwan M.Z., Evans J.J. (2009). Central and peripheral effects of RFamide-related peptide-3 on luteinizing hormone and prolactin secretion in rats. Endocrinology 150: 1834-1840.

Ansel L., Bolborea M., Benten A. H., Klosen P., Mikkelsen J. D., Simonneaux. V. (2010). Differential regulation of kiss1 expression by melatonin and gonadal hormones in male and female Syrian hamster. J. Biol. Rhythms ,25:81-91.

Arendt J. (1986) Role of the pineal gland and melatonin in seasonal reproductive function in mammals. Oxf. Rev. Reprod. Biol., 8: 266-320.

Azouz A., Ateia M.Z., Shawky H., Zakaria A.D., Farahat A. A. Hormonal changes during rutting and the non-breeding season in male dromedary camels. Proc. 1st int. Camel Conf, 1992, Dubai, UAE: 169-171.

Babiker E.A., Ahmed A.I., Husna M.E., Abdel-Aziz B.E. (2011). Serum testosterone and progesterone levels and ovarian activity as indicators for seasonal breeding in dromedary camels in Sudan. 309-312.

Bartness T.J., Powers, J.B., Hastings, M.H., Bittman, E.L. Goldman B.D. (1993). The timed infusion paradigm for melatonin delivery: what has it taught us about the melatonin signal, its reception, and the photoperiodic control of seasonal responses? J. Pineal Res., 15: 161-190.

Bedrak E., Rosenstrauch A., Kafka M., Friedlander M. (1983). Testicular steroidogenesis in the camel (Camelus dromedarius) during the mating and the nonmating seasons. Gen. Comp. Endocrinol., 52: 255-264.

Benaissa M..H., Faye B., Yourgs. R.C., Kaidi R. Slaughterhouse survey of culled female camels (Camelus dromedarius) in southeast Algeria: Fetal wastage and pregnancy characteristics. (2016). Emirates Journal of food and agriculture, 28: 805-812

Bono G., Moallin Dahir A., Comin A., Ahmed Jumale M. (1988). Seasonal variations of LH response to GnRH treatment in camels (C. dromedarius), llth Int. Congr. Anita. Reprod. and A.I: 2: 12.

Bono G., Moallin Dahir A., Comin A., Ahmed Jumale M. (1989). Plasma LH, corticoid and sex steroid variations in camels (Camelus dromedarius) in relation to seasonal climatic changes. Anim. Reprod. Sci., 21: 101-113.

Bouhadou Nezha. (2016). Contrôle par les saisons et la photopériode de la fonction de reproduction chez la gerboise (Jaculus orientalis): Rôle et mécanisme d’action du 5-Métoxytryptophol. thesis defended at Mohamed V –Agdal university, Rabat.

Bronson F.H. (2009). Climate change and seasonal reproduction in mammals. Philos. Trans. R. Soc. B Biol. Sci., 364: 3331-3340.

Caraty A., Franceschini I., Hoffman G. E. (2010). Kisspeptin and the preovulatory gonadotrophin-releasing hormone/luteinising hormone surge in the ewe: basic aspects and potential applications in the control of ovulation. J. Neuroendocrinol., 22:710-715.

Castellano J.M., Navarro V.M., Fernández-Fernández R., Nogueiras R., Tovar S., Roa J., Vazquez M.J., Vigo E., Casanueva F.F., Aguilar E., Pinilla L., Dieguez C., Tena-Sempere M. (2005). Changes in hypothalamic KiSS-1 system and restoration of pubertal activation of the reproductive axis by kisspeptin in undernutrition. Endocrinology, 146: 3917-3925.

Chalivoix S., Bagnolini A., Caraty A., Cognié J., Malpaux B., Dufourny L. (2010). Effects of photoperiod on kisspeptin neuronal populations of the ewe diencephalon in connection with reproductive function. J. Neuroendocrinol., 22: 110–118.

Cheng G., Coolen L.M., Padmanabhan V., Goodman, R.L., Lehman M.N. (2010). The Kisspeptin/Neurokinin B/Dynorphin (KNDy) cell population of the arcuate nucleus: sex differences and effects of prenatal testosterone in sheep. Endocrinology, 151: 301-311.

Clarke I.J., Sari I.P., Qi Y., Smith J.T., Parkington H.C., Ubuka T., Iqbal J., Li Q., Tilbrook A., Morgan K., et al. (2008). Potent action of RFamide-related peptide-3 on pituitary gonadotropes indicative of a hypophysiotropic role in the negative regulation of gonadotropin secretion. Endocrinology, 149: 5811-5821.

Clarkson J., Herbison A.E. (2006). Postnatal development of kisspeptin neurons in mouse hypothalamus; sexual dimorphism and projections to gonadotropin-releasing hormone neurons. Endocrinology, 147: 5817-5825.

Comin A., Gerin D., Cappa A., Marchi V., Renaville R., Motta M., Fazzini U., Prandi A. (2002). The effect of an acute energy deficit on the hormone profile of dominant follicles in dairy cows. Theriogenology, 58: 899-910.

Dardente H., Birnie M,. Lincoln G. A., Hazlerigg D.G. (2008). RFamide-related peptide and its cognate receptor in the sheep: cDNA cloning, mRNA distribution in the hypothalamus and the effect of photoperiod. J. Neuroendocr., 20:1252-1259.

Dardente H. (2012). Melatonin-dependent timing of seasonal reproduction by the pars tuberalis: pivotal roles for long daylengths and thyroid hormones: melatonin-dependent timing of seasonal reproduction by the pars tuberalis. J. Neuroendocrinol., 24: 249–266.

Dardente H., Lomet D., Robert V., Decourt C., Beltramo M., Pellicer-Rubio M.-T. (2016). Seasonal breeding in mammals: From basic science to applications and back. Theriogenology, 86: 324-332.

De Bond J.-A.P., Smith J.T. (2014). Kisspeptin and energy balance in reproduction. Reproduction. 147: R53-R63.

De Roux N., Guenin E., Cartel J.C., Matsuda F., Chaussain J.L., Milgrom E. (2003). Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc. Natl. Acad. Sci., 100: 10972-10976.

Decourt C., Tillet Y., Caraty A., Franceschini I., Briant C. (2008). Kisspeptin immunoreactive neurons in the equine hypothalamus. J. Chem. Neuroanat., 36: 131-137.

Desroziers E., Mikkelsen J., Simonneaux V., Keller M., Tillet Y., Caraty A., Franceschini I. (2010). Mapping of kisspeptin fibres in the brain of the pro-oestrous rat: kisspeptin mapping in the female rat. J. Neuroendocrinol. 22: 1101-1112.

Dholpuria S., Vyas S., Purohit G.N., Pathak K.M.L. (2012). Sonographic monitoring of early follicle growth induced by melatonin implants in camels and the subsequent fertility. Journal of Ultrasound, 15: 135-141

Drijfhout W.J., A.G.van der Linde, J.B. de Vries C.J. Grol B.H.C. Westerink (1996). Microdialysis reveals dynamics of coupling between noradrenaline release and melatonin secretion in conscious rats. Neurosci. Lett., 202:185-188.

Ducret E., Anderson G.M., Herbison A.E. (2009). RFamide-related peptide-3, a mammalian gonadotropin-inhibitory hormone ortholog, regulates gonadotropin-releasing hormone neuron firing in the mouse. Endocrinology, 150: 2799-2804.

Dufourny L., Levasseur A., Migaud M., Callebaut I., Pontarotti P., Malpaux B., Monget, P. (2008). GPR50 is the mammalian ortholog of Mel1c: Evidence of rapid evolution in mammals. BMC Evol. Biol., 8: 105.

Dutt R.H., Leon F.B. (1955). The effect of low environmental temperature on the initiation of the breeding season and fertility in sheep. J. Anim. Sci., 14: 885.

El Allali K., Achaâban M.R., Bothorel B., Piro M., Bouaouda H., Allouchi M.E., Ouassat M., Malan A., Pevet P. (2013). Entrainment of the circadian clock by daily ambient temperature cycles in the camel (Camelus dromedarius). AJP Regul. Integr. Comp. Physiol., 304: R1044–R1052.

El Allali K., Achaâban M.R., Vivien-Roels B., Bothorel B., Tligui N.S., Pévet P. (2005). Seasonal variations in the nycthemeral rhythm of plasma melatonin in the camel (Camelus dromedarius): seasonal plasma melatonin in the camel. J. Pineal Res., 39: 121–128.

El-Harairy M.A., Attia, K.A. (2010). Effect of age, pubertal stage and season on testosterone concentration in male dromedary camel. Saudi J. Biol. Sci., 17: 227-230.

Elias E., Bedrak E., Cohen D. (1985). Induction of oestrus in the camel (Camelus dromedarius) during seasonal anoestrus. J. Reprod. Fertil. 74: 519-525.

Elias E., Degen A. A., Kam M. (1991). Effect of conception date on length of gestation in the dromedary camel (Camelus dromedarius) in the Negev desert. Animal Reproduction Science, 25: 173-177.

Elias E., Bedrak E., Yagil R. (1984). Estradiol concentration in the serum of the one-humped camel (Camelus dromedarius) during the various reproductive stages. Gen. Comp. Endocrinol., 56: 258-264.

Elmi Ahmed A. (1989). Camel husbandry and management by ceeldheer pastoralists in Central Somalia. ISSN 0951-1911 Paper 27d.

Estrada K.M., Clay C.M., Pompolo S., Smith J.T., Clarke I.J. (2006). Elevated KiSS-1 expression in the arcuate nucleus prior to the cyclic preovulatory gonadotrophin-releasing hormone/lutenising hormone surge in the ewe suggests a stimulatory role for kisspeptin in oestrogen-positive feedback. J. Neuroendocrinol. 18: 806-809.

Fat-halla M.M., Ismail A.A. (1980) Seasonal variations in gonadotropins of one-humped male camel (Camelus dromedarius). 9th International Congress on Animal Reproduction and Artificial Insemination, 16th-20th June 1980 III Symposia free communications: 88

Fatnassi M., Padalino B., Monaco D., Khorchani T., Lacalandra G.M., Hammadi M. (2016). Effect of continuous female exposure on behavioral repertoire and stereotypical behaviors in restrained male dromedary camels during the onset of the breeding season. Trop. Anim. Health Prod., 48: 897-903.

Fukusumi S., Habata Y., Yoshida H., Iijima N., Kawamata Y., Hosoya M., Fujii R., Hinuma S., Kitada C., Shintani Y., Suenaga M., Onda H., Nishimura O., Tanaka M., Ibata Y., Fujino M. (2001). Characteristics and distribution of endogenous RFamide-related peptide-1. Biochim. Biophys. Acta, 1540: 221-232.

Garcia-Garcia R.M. (2012). Integrative control of energy balance and reproduction in females. ISRN Vet. Sci., 2012: 1-13.

Gherissi D.E., Afri-Bouzebda F., Bouzebda Z., Lamraoui R. (2016). Testicular morphology and stereological evaluation of the seminiferous tubules around the rutting season of sahraoui dromedary camel. Global Veterinaria. 17: 568-576.

Godley W.C., Wilson R.L., Hurst V. (1966). Effect of controlled environment on the reproductive performance of ewes. J. Anim. Sci. 25: 212-216.

Goldman B.D. (2001) Mammalian photoperiodic system: formal properties and neuroendocrine mechanisms of photoperiodic time measurement. J Biol Rhythms. 16: 283-301.

Goodman R.L., Lehman M.N., Smith J.T., Coolen L.M., de Oliveira C.V.R., Jafarzadehshirazi M.R., Pereira A., Iqbal J., Caraty A., Ciofi P., Clarke J.L. (2007). Kisspeptin neurons in the arcuate nucleus of the ewe express both dynorphin A and neurokinin B. Endocrinology. 148: 5752-5760.

Gottsch M.L., Cunningham M.J., Smith J.T., Popa S.M., Acohido B.V., Crowley W.F., Seminara S., Clifton D.K., Steiner R.A. (2004). A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology. 145: 4073-4077.

Gwinner E. (1981). Annual Rhythms: Perspectives. Handbook of Behavioral Neurobiology. In Aschoff J (ed): “Biological Rhythms”. 4: 381-389.

Hafez E.S.E. (1964). Effects of high temperature on reproduction: A review. Int. J. Biometeorol. 7: 223-230.

Hanon E.A., Routledge K., Dardente H., Masson-Pévet, M., Morgan, P.J., Hazlerigg D.G. (2010). Effect of photoperiod on the thyroid-stimulating hormone neuroendocrine system in the european hamster (Cricetus cricetus). J. Neuroendocrinol. 22: 51-55.

Hansen, P. J. (2009). Effects of heat stress on mammalian reproduction. Philosophical Transactions of the Royal Society of London. A 364: 3341-3350

Henningsen J.B., Poirel V.-J., Mikkelsen J.D., Tsutsui K., Simonneaux V., Gauer F. (2016). Sex differences in the photoperiodic regulation of RF-Amide related peptide (RFRP) and its receptor GPR147 in the syrian hamster: RFRP sex differences in a seasonal rodent. J. Comp. Neurol. 524: 1825-1838.

Hinuma S., Shintani Y., Fukusumi S., Iijima N., Matsumoto Y., Hosoya M., Fujii R., Watanabe T., Kikuchi K., Terao Y., Yano T., Yamamoto T., Kawamata Y., Habata Y., Asada M., Kitada C., Kurokawa T., Onda H., Nishimura O., Tanaka M., Ibata Y., Fujino M. (2000). New neuropeptides containing carboxy-terminal RFamide and their receptor in mammals. Nat. Cell Biol. 2: 703-708.

Hoffman K. (1979). Photoperiod, pineal, melatonin and reproduction in hamster. Prog. Brain. Res. 52: 397-415.

Hrabovszky E., Ciofi P., Vida B., Horvath M.C., Keller E., Caraty A., Bloom S.R., Ghatei M.A., Dhillo W.S., Liposits Z., Kallo I. (2010). The kisspeptin system of the human hypothalamus: sexual dimorphism and relationship with gonadotropin-releasing hormone and neurokinin B neurons: Kisspeptin neurons in the human. Eur. J. Neurosci. 31: 1984-1998.

Ibrahim Z.H., Joshi D., Singh S.K. (2016). Seasonal immunohistochemical reactivity of S-100 and α-smooth muscle actin proteins in the epididymis of dromedary camel, Camelus dromedarius. Andrologia.

Illnerova H., Hoffman K., Vanecek J. (1984) Adjustment of pineal melatonin and N-acetyltransferase rhythms to change from long to short photoperiod in the Djungarian hamster Phodopus sungorus. Neuroendocrinology. 38: 226-231.

Irwig M.S., Fraley G.S., Smith J.T., Acohido B.V., Popa S.M., Cunningham M.J., Gottsch M.L., Clifton D.K., Steiner R.A. (2004). Kisspeptin activation of gonadotropin releasing hormone neurons and regulation of KiSS-1 mRNA in the male rat. Neuroendocrinology. 80: 264-272.

Ismail A. A., Radwan Y. M., El-Bdary A. A., El-Mougy SS A. Patterns of prolactin, FSH and TSH levels in the malone humped camel. 1st Nat. Conf. Physiol. Sci, 1984, Cairo, Egypt.

Janati A., Talbi R., Klosen P., Mikkelsen J.D., Magoul R., Simonneaux V., El Ouezzani S. (2013). Distribution and seasonal variation in hypothalamic RF-amide peptides in a semi-desert rodent, the jerboa. J. Neuroendocrinol. 25: 402-411.

Johnson M.A., Tsutsui K., Fraley G.S. (2007). Rat RFamide-related peptide-3 stimulates GH secretion, inhibits LH secretion and has variable effects on sex behavior in the adult male rat. Horm. Behav. 51: 171-180.

Kanai Y., Yagyu N., Shimizu T. (1995). Hypogonadism in heat stressed goats: poor responsiveness of the ovary to the pulsatile LH stimulation induced by hourly injections of a small dose of GnRH. J. Reprod. Dev. 41: 133-139.

Kauffman A.S., Gottsch M.L., Roa J., Byquist A.C., Crown A., Clifton D.K., Hoffman G.E., Steiner R.A., Tena-Sempere M. (2007). Sexual differentiation of Kiss1 gene expression in the brain of the rat. Endocrinology. 148: 1774-1783.

Khaldoun, M. (1990). Reproductive potentialities of one humped she-camel. Adaptation to environment. Proceedings of the workshop ‘Is it possible to improve the reproductive Performance of the camel?, Paris: 37-50.

Khanna N. D., Tandon S. N., Rai A. K. (1990). Breeding parameters of Indian camels. Indian Journal of Animal Sciences 60: 1347-1354

King T.S et Steinlechner S. (1985) Pineal indolalkylamine synthesis and metabolism: kinetic considerations. Pineal Res. Rev., 3: 69–113.

Klosen P., Sebert M.E., Rasri K., Laran-Chich M.P., Simonneaux V. (2013). TSH restores a summer phenotype in photoinhibited mammals via the RF-amides RFRP3 and kisspeptin. FASEB J. 27: 2677-2686.

Kotani M., Detheux M., Vandenbogaerde A., Communi D., Vanderwinden J.M., Le Poul E., Brézillon S., Tyldesley R., Suarez-Huerta N., Vandeput F., Blanpain C., Schiffmann S.N., Vassart G., Parmentier M. (2001). The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J. Biol. Chem. 276: 34631-34636.

Kriegsfeld L.J., Mei D.F., Bentley G.E., Ubuka T., Mason A.O., Inoue K., Ukena K., Tsutsui K., Silver R. (2006). Identification and characterization of a gonadotropin-inhibitory system in the brains of mammals. Proc. Natl. Acad. Sci. U.S.A. 103: 2410-2415.

Larsen P.J., Enquist L.W., Card J.P. (1998) Characterization of the multisynaptic neuronal control of the rat pineal gland using viral transneuronal tracing. Eur. J. Neurosci.10: 128-145.

Lee J.H., Miele M.E., Hicks D.J., Phillips K.K., Trent J.M., Weissman B.E., and Welch D.R. (1996). KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J. Natl. Cancer Inst., 88: 1731-1737.

Lehman M.N., Hileman S.M., Goodman R.L. (2014). Neuroanatomy of the Kisspeptin Signaling System in Mammals: comparative and Developmental Aspects. Adv Exp Med Biol., 784: 27-62.

Li H., Song H., Huang M., Nie H., Wang Z., Wang F. (2014). Impact of food restriction on ovarian development, RFamide-related peptide-3 and the hypothalamic–pituitary–ovarian axis in pre-pubertal ewes. Reproduction in Domestic Animals. 49: 831-838.

Lincoln G.A. (1979). Photoperiodic control of seasonal breeding in the ram: Participation of the cranial pathetic nervous system. J. Endocrinol., 82: 135 – 147.

Lincoln G.A, Short R.V. (1980). Seasonal breeding: nature’s contraceptive. Recent. Prog. Horm. Res., 36: 1-52.

Lincoln G.A. (1992). Administration of melatonin into the mediobasal hypothalamus as a continuous or intermittent signal affects the secretion of follicle stimulating hormone and prolactin in the ram. J. Pineal. Res., 122: 135-144.

Lincoln G. A, Richardson M. (1998). Photoneuroendocrine control of seasonal cycles in body weight, pelage growth and reproduction: lessons from the HPD sheep model. Comp Biochem physiol C Pharmacol Toxicol Endocrinol. 119: 283-294.

Lincoln G.A., Rhind S.M., Pompolo S., Clarke I.J. (2001). Hypothalamic control of photoperiod-induced cycles in food intake, boody weight, and metabolic horomones in rams. Am. J. Physiol. Regul. Integr. Comp. Physiol., 281: R76-90.

Lofts B. (1975). Animal Photoperiodism. In Arnold E (ed): “The institute of Biology’s Studies in Biology”.

Magee C., Foradori C.D., Bruemmer J.E., Arreguin-Arevalo J.A., McCue P.M., Handa R.J., Squires E.L., Clay C.M. (2009). Biological and anatomical evidence for kisspeptin regulation of the hypothalamic-pituitary-gonadal axis of estrous horse mares. Endocrinology, 150: 2813-2821.

Mahmoud S.A. (2006). Histological and histochemical studies on the endometrium of the she-camel in relation to ovarian activity. PhD Thesis. Cairo Uni., Egypt

Malpaux B., Thiéry J.C., Chemineau P. (1999). Melatonin and the seasonal control of reproduction. Reprod. Nutr. Dev., 39: 355-366.

Manjunatha B.M., Al-Bulushi S., Pratap N. (2015). Synchronisation of the follicular wave with GnRH and PGF2α analogue for a timed breeding programme in dromedary camels (Camelus dromedarius). Anim. Reprod. Sci. 160: 23–29.

Manning J., Bronson F.H. (1990). The effects of low temperature and food intake on ovulation in domestic mice. Physiol. Zool. 63: 938-948.

Margetic S., Gazzola., Peg G.G., Hill R.A. (2002). Leptin: A review of its peripheral actions and interactions. International Journal of Obesity, 26: 1407-1433.

Marie M.E. (1987). Bases neuroendocriniennes de la fonction sexuelle chez le dromadaire (Camelus dromedarius). Thèse de doctorat de l’Université Paris 6.

Mason A., Greives T., Scotti M., Levine J., Frommeyer S., Ketterson E., Demas G., Kriegsfeld L. (2007). Suppression of kisspeptin expression and gonadotropic axis sensitivity following exposure to inhibitory day lengths in female Siberian hamsters. Horm. Behav., 52: 492-498.

Mayouf R., Benaissa M.H., Benria Y., Aoune F.Z., Halis Y., (2014) Reproductive performance of camelus dromedarius in the el-oued region, Algeria. Online Journal of Animal and Feed Research Volume 4, Issue 4: 102-106.

McKnight T.L. (1969). The Camel in Australia. Melbourne: Melbourne University Press.

Misztal T., Romanowicz K., Barcikowski B. (2002). Effect of melatonin on daily LH secretion in intact and ovariectomized ewes during the breeding season. Anim. Reprod. Sci., 69: 187-198.

Moslam M., Megdiche F. (1989). L’élevage camelin en Tunisie. Cahiers Options méditerranéennes série A n°2 ; pp : 33-36.

Muir A.I., Chamberlain L., Elshourbagy N.A., Michalovich D., Moore D.J., Calamari A., Szekeres P.G., Sarau H.M., Chambers J.K., Murdock P., Steplewskit K., Shabon U., Miller J.E., Middleton S.E., Darker J.G., Larminie C.G.C., Wilson S., Bergsma D.J., Emson P., Faulli R., Philpott K.L., Harrison D.C. (2001). AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1. J. Biol. Chem., 276: 28969-28975.

Mukasa-Mugerwa E. (1981). The camel (Camelus dromedarius): a bibliographical review. ILCA-Monograph Int. Livestock Centre for Africa: 11-32.

Murphy B.A, Walsh C.M., Woodward E.M., Prendergast R.L., Ryle J.P., Fallon L.H., Troedsson M.H.T. (2014). Blue light from individual light masks directed at a single eye advances the breeding season in mares. Equine Veterinary Journal, 46: 601-605.

Musa B., Sieme H., Merkt H., Hago B., Cooper M.J., Allen W.R., and Jöchle W. (1993). Manipulation of reproductive functions in male and female camels. Anim. Reprod. Sci., 33: 289-306.

Nakao N., Ono H., Yamamura T., Anraku T., Takagi T., Higashi K., Yasuo S., Katou Y., Kageyama S., Uno Y., Kasukawa T., Iigo M., Sharp P.J., Iwasawa A., Suzuki Y., Sugano S., Niimi T., Mizutani M., Namikawa T., Ebihara S., Ueda H.R., Yoshimura T. (2008). Thyrotrophin in the pars tuberalis triggers photoperiodic response. Nature, 452: 317-322.

Ohtaki T., Shintani Y., Honda S., Matsumoto H., Hori A., Kanehashi K., Terao Y., Kumano S., Takatsu Y., Masuda, Y., Ishibashi Y., Watanabe T., Asada M., Yamada T., Suenaga M., Kitada C., Usuki S., Kurokawa T., Onda H., Nishimura O., Fujino M. (2001). Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature, 411: 613–617.

Ozawa M., Tabayashi D., Latief T.A., Shimizu T., Oshima I., Kanai Y. (2005). Alterations in follicular dynamics and steroidogenic abilities induced by heat stress during follicular recruitment in goats. Reproduction, 129: 621-630.

Pévet P., Vivien-Roels B., Masson-Pévet M. (1991) Annual changes in the daily pattern of melatonin synthesis and release. in role of melatonin and pineal peptides in neuroimmunomodulatin. Fraschini F, Reiter RJ, eds. Plenum press, New York. 147-158.

Pineda R., Garcia-Galiano D., Sanchez-Garrido M.A., Romero M., Ruiz-Pino F., Aguilar E., Dijcks F.A., Blomenröhr M., Pinilla L., van Noort P.I., (2010). Characterization of the inhibitory roles of RFRP3, the mammalian ortholog of GnIH, in the control of gonadotropin secretion in the rat in vivo and in vitro studies. Am. J. Physiol. Endocrinol. Metab., 299: E39-E46.

Ramaswamy S., Guerriero K.A., Gibbs R.B., Plant T.M. (2008). Structural interactions between kisspeptin and GnRH neurons in the mediobasal hypothalamus of the male rhesus monkey (Macaca mulatta ) as revealed by double immunofluorescence and confocal microscopy. Endocrinology, 149: 4387-4395.

Reiter R.J (1974). Circannual reproductive rhythms in mammals related to photoperiod and pineal function: A review. Chronobiologia, 1: 365-394.

Reiter R.J. (1978). Interaction of photoperiod, pineal and seasonal reproduction as exemplified by finding in the hamster. Prog. Reprod. Biol., 4: 169-190.

Reiter R. J. (1981). The pineal gland, Vol II. Reproductive effects. Boca Raton: CRC Press.

Reiter RJ. (1986) Normal patterns of melatonin levels in the pineal gland and body fluids of humans and experimental animals. J. Neural. Transm. Suppl., 21: 35-54.

Reiter R.J. (1993). The melatonin rhythm: both a clock and a calendar. Experientia, 49: 654-664.

Reppert S.M., Weaver D.R., Godson C. (1996). Melatonin receptors step into the light: cloning and classification of subtypes. Trends Pharmacol. Sci., 17: 100–102.

Revel F.G., Saboureau M., Masson-Pévet M., Pévet P., Mikkelsen J.D., Simonneaux V. (2006). Kisspeptin mediates the photoperiodic control of reproduction in Hamsters. Curr. Biol., 16: 1730-1735.

Revel F.G., Saboureau M., Pévet P., Simonneaux V., Mikkelsen J.D. (2008). RFamide-related peptide gene is a melatonin-driven photoperiodic gene. Endocrinology, 149: 902–912.

Rizwan, M.Z., Poling, M.C., Corr, M., Cornes, P.A., Augustine, R.A., Quennell, J.H., Kauffman A.S., Anderson G.M. (2012). RFamide-related peptide-3 receptor gene expression in GnRH and kisspeptin neurons and GnRH-dependent mechanism of action. Endocrinology, 153: 3770-3779.

Rometo A.M., Krajewski, S.J., Lou Voytko, M., Rance, N.E. (2007). Hypertrophy and increased kisspeptin gene expression in the hypothalamic infundibular nucleus of postmenopausal women and ovariectomized monkeys. J. Clin. Endocrinol. Metab., 92: 2744–2750.

Rosa H.J., Bryant M. (2003). Seasonality of reproduction in sheep. Small Rumin. Res., 48: 155-171.

Sghiri A. et Driancourt M.A. (1999). Seasonal effects on fertility and ovarian follicular growth and maturation in camels (Camelus dromedarius). Anim. Reprod. Sci., 55: 223-237.

Sicard B., Maurel D., Fuminier F., Biossin J. (1992) circadian rhythm of photosensitivity and the adaptation of reproductive function to the environment in two populations of Arvicanthis niloticus from Mali and Burkina Faso. J. Reprod. Fert., 95: 159-165.

Sigh U.B., Bharadwaj M.B. (1978). Morphological changes in the testis and epididymis of camels (Camelus dromedarius). Part I. Acta Anat., (Basel) 101: 275-279.

Seminara S. B., Messager S., Chatzidaki E. E., Thresher R.R., Acierno J. S., Shagoury J.K., Bo-Abbas Y., Kuohung W., Schwinof K.M., Hendrick A.G., Zahn D., Dixon J., Kaiser U.B., Slaugenhaupt S.A., Gusella J.F., O’Rahilly S., Carlton M.B.L., Crowley W.F., Aparicio S.A.J.R., Colledge W.H. (2003) The GPR54 gene as a regulator of puberty. N. Engl. J. Med., 3: 1614-1627.

Smith J.T., Acohido B.V., Clifton D.K., Steiner R.A. (2006). KiSS-1 neurones are direct targets for leptin in the ob/ob mouse. J. Neuroendocrinol., 18: 298-303.

Smith J.T., Clay C.M. Caraty A., Clarke I.J. (2007). KiSS-1 messenger ribonucleic acid expression in the hypothalamus of the ewe is regulated by sex steroids and season. Endocrinology, 148: 1150-1157.

Smith J. T., Coolen L. M., Kriegsfeld L. J., Sari I. P., Jaafarzadehshirazi M. R., Maltby M., Bateman K., Goodman R. L., Tilbrook A. J., Ubuka T., Bentley G. E., Clarke I. J., Lehman M. N. (2008) Variation in kisspeptin and RFamide-relate d peptide (RFRP) expression and terminal connections to gonadotropin-releasing hormone neurons in the brain: a novel medium for seasonal breeding in the sheep. Endocrinology, 149: 5770-82.

Smith J.T., Cunningham M.J., Rissman E.F., Clifton D.K., Steiner R.A. (2005). Regulation of Kiss1 gene expression in the brain of the female mouse. Endocrinology, 146: 3686-3692.

Stehle J.H., Von Gall C., Schomerus C., Korf H.W. (2001). Of rodents and ungulates and melatonin: creating a uniform code for darkness by different signaling mechanisms. J. Biol. Rhythms, 16: 312-325.

Swelum A., Saadeldin I., Ba-Awadh H., Alowaimer A. (2016). 110 Effect of melatonin treatment on libido and endocrine function of dromedary camel bulls out of the breeding season. Reprod. Fertil. Dev., 29:163-164.

Talbi R., Laran-Chich M.P., Magoul R., El Ouezzani S., Simonneaux V. (2016). Kisspeptin and RFRP-3 differentially regulate food intake and metabolic neuropeptides in the female desert jerboa. Scientific Reports. 6, Article number: 36057.

Tast A., Halli O., Ahlstrom S., Andersson H., Love R.J., Peltoniemi O.A.T. (2001). Seasonal alterations in circadian melatonin rhythms of the european wild boar and domestic gilt. J. Pineal. Res., 30: 43-49.

Teclemariam-Mesbah R, Ter Horst GJ, Postema F., Wortel J., Buijs R.M. (1999). Anatomical demonstration of the suprachiasmatic nucleuspineal pathway. J. Comp. Neurol., 406: 171-182.

Tibary A., Anouassi A. (1997). Theriogenology in camelidae: anatomy, physiology, pathology surgery and artificial breeding. Institut Agronomique et Vétérinaire Hassan II. Actes Edition, Rabat, Morocco 1997. ISBN 9981-801-32-1.

Tingari, M.D., Ramos A.S., Gaili E.S.E., Rahma B.A. and Saad A.H.. (1984). Morphology of the testis of the onehumped camel in relation to reproductive activity. J. Anat., 139:133-143.

Traoré B., Moula N., Toure A., Ouologuem B., Leroy P., Antoine-Moussiaux N. (2014). Characterisation of camel breeding practices in the Ansongo Region, Mali. Trop. Anim. Health Prod., 46: 1303-1312.

Ubuka T., Inoue, K., Fukuda Y., Mizuno T., Ukena K., Kriegsfeld L.J., Tsutsui K. (2012). Identification, expression, and physiological functions of Siberian hamster gonadotropin-inhibitory hormone. Endocrinology, 153: 373-385.

Ukena K., Iwakoshi E., Minakata H., Tsutsui K. (2002). A novel rat hypothalamic RFamide-related peptide identified by immunoaffinity chromatography and mass spectrometry. FEBS Lett., 512: 255-258.

Vanĕcek J., Pavlík A., Illnerová, H. (1987). Hypothalamic melatonin receptor sites revealed by autoradiography. Brain Res., 435: 359-362.

Vivien-Roels B., Pevet P. (1983). The Pineal gland and the synchronization of reproductive cycles with variations of the environmental climatic conditions, with special reference to temperature. Pineal Research reviews, 1: 91-143.

Vyas S., Ravault J.P., Faye B., Chemineau P. (1997) The nycthemeral rhythm of melatonin secretion in camel (Camelus dromedarius). Rev. Elev. Méd. Vét. Pays Trop., 50: 250-260.

Vyas S., RaghvendraS., Govind N. .P., Pareek P.K., Sahani M.S. (2008). Ultrasound evaluation of ovarian response to photoperiodic control measures in Camelus dromedarius. Veterinarski Arhiv., 78: 39-48.

Wagner G.C., Johnston J.D., Clarke I.J., Lincoln G.A., Hazlerigg D.G. (2008). Redefining the limits of day length responsiveness in a seasonal mammal. Endocrinology, 149: 32-39.

Weaver D.R., Rivkees S.A., Reppert S.M. (1989). Localization and characterization of melatonin receptors in rodent brain by in vitro autoradiography. J. Neurosci. Off. J. Soc. Neurosci., 9: 2581-2590.

Williams L.M., Morgan P.J., Hastings M.H., Lawson W., Davidson G., Howell H.E. (1989). Melatonin receptor sites in the syrian hamster brain and pituitary. Localization and characterization using [125]lodomelatonin. J. Neuroendocrinol., 1: 315-320.

Wilson R.T. (1986). Reproductive performance and survival of young one-humped camels on Kenya commercial ranches. Anim. Prod., 42: 375-380.

Yagil R., Etzion Z. (1980). Hormonal and behavioural patterns in the male camel (Camelus dromedarius). J. Reprod. Fertil., 58: 61-65.

Yagil R., Etzion Z. (1984). Enhanced reproduction in camels (Camelus dromedaries). Comparative Biochemistry and Physiology, 79: 201-204.

Yasin S.A., Wahid A. (1957) Pakistan camels: a preliminary survey. Agri. Pak., 8: 289-297.

Zhang, C., Bosch M.A., Levine J.E., Ronnekleiv O.K., Kelly M.J. (2007). Gonadotropin-releasing hormone neurons express KATP channels that are regulated by estrogen and responsive to glucose and metabolic inhibition. J. Neurosci., 27: 10153-10164.

Zia-ur-Rahman A.N., Bukhari S.A., Akhtar N., Haq I.U. (2007). Serum hormonal, electrolytes and trace element profiles in the rutting and non-rutting one-humped male camel (Camelus dromedarius). Anim. Reprod. Sci., 101: 172–178.

http://otaff.ca/soleil/?lang=en_CA version published by the Free Software Foundation. consulted 15/03/2017

http://fr.climate-data.org. consulted 15/03/2017