A role for GnRH in olfaction and cognition: Implications for veterinary medicine.

Pulsatile secretion of gonadotropin-releasing hormone (GnRH) is essential for the activation and maintenance of the function of the hypothalamic-pituitary-gonadal (HPG) axis, which controls the onset of puberty and fertility. Two provocative recent studies suggest that, in addition to control reproduction, the neurons in the brain that produce GnRH are also involved in the control postnatal brain maturation, odour discrimination and adult cognition. Long-acting GnRH antagonists and agonists are commonly used to control fertility and behaviour in veterinary medicine, primarily in males. This review puts into perspective the potential risks of these androgen deprivation therapies and immunization on olfactory and cognitive performances and well-aging in domestic animals, including pets. We will also discuss the results reporting beneficial effects of pharmacological interventions restoring physiological GnRH levels on olfactory and cognitive alterations in preclinical models of Alzheimer's disease, which shares many pathophysiological and behavioural hallmarks with canine cognitive dysfunction. These novel findings raise the intriguing possibility that pulsatile GnRH therapy holds therapeutic potential for the management of this behavioural syndrome affecting older dogs.

Highly-Sensitive In Vitro Bioassays for FSH, TSH, PTH, Kp, and OT in Addition to LH in Mouse Leydig Tumor Cell.

We demonstrate here that highly sensitive in vitro bioassays for FSH, TSH, and PTH can be set up in mouse Leydig Tumor Cells (mLTC), in addition to the normal LH/CG bioassay, after they were transfected with expression vectors encoding the corresponding Gs Protein-Coupled Receptors (GsPCR), such as FSHR, TSHR, or PTHR. Although the ß2 adrenergic receptor is also a GsPCR, its expression in mLTC led to a significant but very low cAMP response compared to those observed with FSH, TSH, or PTH. Similarly, after transfection of the GiPCR MT1 melatonin receptor, we did not observe any inhibitory effect by melatonin of the LH or hCG stimulation. Interestingly, after transfection of mLTC with the human kisspeptin receptor (hKpR), which is a GqPCR, we observed a dose-dependent synergy of 10-12-10-7 M kisspeptin variants with a fixed concentration of 0.3 nM LH or hCG. Without any exogenous receptor transfection, a 2 h preincubation with OT or AVP led to a dose-dependent cAMP response to a fixed dose of LH or hCG. Therefore, highly sensitive in vitro bioassays for various hormones and other GPCR ligands can be set up in mLTC to measure circulating concentrations in only 3-10 µL of blood or other body fluids. Nevertheless, the development of an LHRKO mLTC cell line will be mandatory to obtain strict specificity for these bioassays to eliminate potential cross-reaction with LH or CG.

Rostro-caudal maturation of glial cells in the accessory olfactory system during development: involvement in outgrowth of GnRH neurites.

During mammalian embryonic development, GnRH neurones differentiate from the nasal placode and migrate through the nasal septum towards the forebrain. We previously showed that a category of glial cells, the olfactory ensheathing cells (OEC), forms the microenvironment of migrating GnRH neurones. Here, to characterize the quantitative and qualitative importance of this glial, we investigated the spatiotemporal maturation of glial cells in situ and the role of maturing glia in GnRH neurones development ex vivo. More than 90% of migrating GnRH neurones were found to be associated with glial cells. There was no change in the cellular microenvironment of GnRH neurones in the regions crossed during embryonic development as glial cells formed the main microenvironment of these neurones (53.4%). However, the phenotype of OEC associated with GnRH neurones changed across regions. The OEC progenitors immunoreactive to brain lipid binding protein formed the microenvironment of migrating GnRH neurones from the vomeronasal organ to the telencephalon and were also present in the diencephalon. However, during GnRH neurone migration, maturation of OEC to [GFAP+] state (glial fibrillary acid protein) was only observed in the nasal septum. Inducing depletion of OEC in maturation, using transgenic mice expressing herpes simplex virus thymidine kinase driven by the GFAP promoter, had no impact on neurogenesis or on triggering GnRH neurones migration in nasal explant culture. Nevertheless, depletion of [GFAP+] cells decreased GnRH neurites outgrowth by 57.4%. This study suggests that specific maturation of OEC in the nasal septum plays a role in morphological differentiation of GnRH neurones.

Olfactory ensheathing cells form the microenvironment of migrating GnRH-1 neurons during mouse development.

During development, GnRH-1 neurons differentiate extracerebraly from the nasal placode and migrate from the vomeronasal organ to the forebrain along vomeronasal and terminal nerves. Numerous studies have described the influence of different molecules on the migration of GnRH-1 neurons, however, the role of microenvironment cells remains poorly understood. This study used GFAP-GFP transgenic mice to detect glial cells at early developmental stages. Using nasal explant cultures, the comigration of glial cells with GnRH-1 neurons was clearly demonstrated. This in vitro approach showed that glial cells began migrating from the explants before GnRH-1 neurons. They remained ahead of the GnRH-1 migratory front and stopped migrating after the GnRH-1 neurons. The association of these glial cells with the axons combined with gene expression analysis of GFAP-GFP sorted cells enabled them to be identified as olfactory ensheathing cells (OEC). Immunohistochemical analysis revealed the presence of multiple glial cell-type markers showing several OEC subpopulations surrounding GnRH-1 neurons. Moreover, these OEC expressed genes whose products are involved in the migration of GnRH-1 neurons, such as Nelf and Semaphorin 4. In situ data confirmed that the majority of the GnRH-1 neurons were associated with glial cells along the vomeronasal axons in nasal septum and terminal nerves in the nasal forebrain junction as early as E12.5. Overall, these data demonstrate an OEC microenvironment for migrating GnRH-1 neurons during mouse development. The fact that this glial cell type precedes GnRH-1 neurons and encodes for molecules involved in their nasal migration suggests that it participates in the GnRH-1 system ontogenesis.

LIMK2d, a truncated isoform of Lim kinase 2 regulates neurite growth in absence of the LIM kinase domain.

Lim kinase 2 isoforms, LIMK2a and LIMK2b, phosphorylate cofilin leading to remodeling of actin cytoskeleton during neuronal differentiation. The expression and function of the LIMK2d isoform, missing the kinase domain, remain unknown. We analyzed the expression of LIMK2 splice variants in adult rat brain and in cultures of rat neural stem cells by RT-QPCR. All three splice variants were expressed in adult cortex, hippocampus and cerebellum. Limk2a and Limk2d expression, but not Limk2b, increased during neuronal differentiation. We studied the localization and function of LIMK2d isoform by transfecting Hela, NSC-34, and hippocampal rat neuron cultures. Similarly to LIMK2b, LIMK2d was expressed in the cytoplasm, neurites and dendritic spines, but not in the nucleus. Similarly to LIMK2a, LIMK2d over-expression in NSC-34 cells increased neurite length, but independently of cofilin phosphorylation or of direct interaction with actin. Overall, these results indicate that LIMK2d is a third LIMK2 isoform which regulates neurite extension and highlights the possible existence of a kinase independent function of LIMK2.

Spike detection for calcium activity.

We present in this paper a global methodology for the spike detection in a biological context of fluorescence recording of GnRH-neurons calcium activity. For this purpose we first propose a simple stochastic model that could mimic experimental time series by considering an autoregressive AR(1) process with a linear trend and specific innovations involving spiking times. Estimators of parameters with asymptotic normality are established and used to set up a statistical test on estimated innovations in order to detect spikes. We compare several procedures and illustrate on biological data the performance of our procedure.

The great migration: How glial cells could regulate GnRH neuron development and shape adult reproductive life.

In mammals, reproductive function is under the control of hypothalamic neurons named Gonadotropin-Releasing Hormone (GnRH) neurons. These neurons migrate from the olfactory placode to the brain, during embryonic development. For the past 40 years, these neurons have been considered an example of tangential migration, i.e., dependent on the olfactory/vomeronasal/terminal nerves. Numerous studies have highlighted the factors involved in the migration of these neurons but thus far overlooked the cellular microenvironment that produces them. Many of these factors are dysregulated in hypogonadotropic hypogonadism, resulting in subfertility/infertility. Nevertheless, over the past ten years, several papers have reported the influence of glial cells (named olfactory ensheathing cells [OECs]) in the migration and differentiation of GnRH neurons. This review will describe the atypical origins, migration, and differentiation of these neurons, focusing on the latest discoveries. There will be a more specific discussion on the involvement of OECs in the development of GnRH neurons, during embryonic and perinatal life; as well as on their potential implication in the development of congenital or idiopathic hypogonadotropic hypogonadism (such as Kallmann syndrome).

Development of the gonadotropin-releasing hormone system.

This review summarizes the current understanding of the development of the neuroendocrine gonadotropin-releasing hormone (GnRH) system, including discussion on open questions regarding (1) transcriptional regulation of the Gnrh1 gene; (2) prenatal development of the GnRH1 system in rodents and humans; and (3) paracrine and synaptic communication during migration of the GnRH cells.

How does apelin affect LH levels? An investigation at the level of GnRH and KNDy neurons.

Hypothalamic control of reproduction relies on GnRH and kisspeptin (KP) secretions. KP neurons are sensitive to sex steroids and metabolic status and their distribution overlaps with neurons producing apelin, a metabolic hormone known to decrease LH secretion in rats. Here, we observed neuroanatomical contacts between apelin fibers and both KP and GnRH neurons in the hypothalamus of male rodents. Intracerebroventricular apelin infusion for 2 weeks in male mice did not decrease LH levels nor did it affect gene expression for KP, neurokinin B and dynorphin. Finally, increasing apelin concentrations did not modulate Ca2+ levels of cultured GnRH neurons, while 10 µM apelin infusion on forskolin pretreated GnRH neurons revoked a rhythmic activity in 18% of GnRH neurons. These results suggest that acute apelin effect on LH secretion does not involve modulation of gene expression in KP neurons but may affect the secretory activity of GnRH neurons.

Gonadotrophin-releasing hormone and kisspeptin: It takes two to tango.

Kisspeptin (Kp), a family of peptides comprising products of the Kiss1 gene, was discovered 20 years ago; it is recognised as the major factor controlling the activity of the gonadotrophin-releasing hormone (GnRH) neurones and thus the activation of the reproductive axis in mammals. It has been widely documented that the effects of Kp on reproduction through its action on GnRH neurones are mediated by the GPR54 receptor. Kp controls the activation of the reproductive axis at puberty, maintains reproductive axis activity in adults and is involved in triggering ovulation in some species. Although there is ample evidence coming from both conditional knockout models and conditional-induced Kp neurone death implicating the Kp/GPR54 pathway in the control of reproduction, the mechanism(s) underlying this process may be more complex than a sole direct control of GnRH neuronal activity by Kp. In this review, we provide an overview of the recent advances made in elucidating the interplay between Kp- and GnRH- neuronal networks with respect to regulating the reproductive axis. We highlight the existence of a possible mutual regulation between GnRH and Kp neurones, as well as the implication of Kp-dependent volume transmission in this process. We also discuss the capacity of heterodimerisation between GPR54 and GnRH receptor (GnRH-R) and its consequences on signalling. Finally, we illustrate the role of mathematical modelling that accounts for the synergy between GnRH-R and GPR54 in explaining the role of these two receptors when defining GnRH neuronal activity and GnRH pulsatile release.

Conditional inactivation of androgen receptor gene in the nervous system: effects on male behavioral and neuroendocrine responses.

Testosterone (T) profoundly influences central sexual differentiation and functions. In the brain, T signals either directly through androgen receptor (AR) or indirectly through estrogen receptor (ER) following aromatization into E2 (17-beta-estradiol). As T, through AR, also controls peripheral male sexual differentiation, the relative contribution of central AR in T-mediated regulation of behavioral and neuroendocrine responses still remains unclear. To address this question, we generated, by using Cre-loxP technology, mice selectively lacking AR expression in the nervous system. The mutant male urogenital tract was normally developed, and mice were able to produce offspring. Nonetheless, sexual motivation and performance as well as aggressive behaviors were affected. Only a low percentage of males displayed a complete sexual behavior and offensive attacks. The latency to show masculine behaviors was increased and copulation length prolonged. Erectile activity during mating was also altered. These alterations occurred despite increased levels of T and its metabolites, and an unaffected number of ERalpha-immunoreactive cells. Olfactory preference and neuronal activation, mapped by Fos immunoreactivity, following exposure to estrus female-soiled bedding were also normal. At comparable T levels, greater differences in masculine behaviors were observed between gonadectomized control and mutant males. AR invalidation in the nervous system also disrupted the somatotropic axis since mutant males exhibited growth retardation and decreased serum levels of insulin-like growth factor I. Our findings show that central AR is required in T-induced regulation of male-typical behaviors and gonadotrope and somatotropic axes. This genetic model offers a unique opportunity in the understanding of AR's role in cerebral functions of T.

The intimate relationship of gonadotropin-releasing hormone neurons with the polysialylated neural cell adhesion molecule revisited across development and adult plasticity.

The neurohormone gonadotropin-releasing hormone (GnRH) is critical for all the aspects of reproductive life in vertebrates. GnRH is secreted by a small number of neurons dispersed within the preoptic-hypothalamic region. These neurons are derived from the embryonic olfactory pit. They then migrate along olfactory, vomeronasal and terminal nerves to their final destination. Classical approaches to study the regulation of GnRH secretion during the reproductive cycle have focused on the various neuronal inputs on GnRH neurons and their regulation by ovarian steroids. However, it is well known that steroids will change the microenvironment of neuronal networks and can induce plasticity and functional changes. In this review, we will focus on the intimate relationship of developing and adult GnRH neurons with the polysialylated form of neural cell adhesion molecule (PSA-NCAM), a major molecular actor in the morphogenesis and adult plasticity of the nervous system. We will first recapitulate the spatiotemporal relationship between PSA-NCAM and migrating GnRH neurons during embryogenesis of various vertebrate species and discuss its importance for GnRH neuron development as shown by various loss of function studies. In the adult, we will review the relationships between PSA-NCAM and GnRH neurons across various physiological states, and open the discussion to the use of new model systems that can help to unravel the function and mechanism of action of PSA-NCAM on GnRH neuronal network activity and GnRH release.

Emerging new sites for adult neurogenesis in the mammalian brain: a comparative study between the hypothalamus and the classical neurogenic zones.

In adult mammalian brain, two main germinative regions located in the subventricular zone of the lateral ventricle and in the subgranular cell layer of the hippocampal dentate gyrus have been considerably documented and are still under intense scrutiny. However, new neuron formation has recently been reported in various other brain areas including the hypothalamus. This central structure, responsible for the control of many major neuroendocrine functions such as reproduction, expresses high levels of PSA-NCAM and nestin, both proteins being involved in structural and morphological plasticity mechanisms. Cell proliferation and new neuron production have been demonstrated in the adult hypothalamus of numerous species, although not hitherto described in non-human primates and humans. Similarly to the subventricular zone and in the subgranular cell layer, the adult hypothalamic neurogenesis process is subject to dynamic regulation by various physiological and pharmacological signals. Several pieces of evidence support the hypothesis that a stem cell niche-like architecture exist in the hypothalamus region lining the third ventricle thereby enabling adult neural stem cells to continuously generate neurons in vivo throughout life. Furthermore, recent data indicating that new hypothalamic neurons may become functionally implicated in sensory information processing endorse the assumption that the hypothalamus might be a neurogenic region.

Endocrine characterization of the reproductive axis in highly prolific lacaune sheep homozygous for the FecLL mutation.

A prolific allele named FecL(L) is known to segregate in the meat breed of the French Lacaune sheep on the basis of ovulation rate record. To gain more knowledge about the physiological effects of FecL(L), ewes homozygous for FecL(L) (L/L) were compared to wild-type ewes (+/+) for ovarian phenotype and reproductive endocrine profiles. At the ovarian level, the increased ovulation rate in L/L ewes was associated with an increased number of antral follicles of greater than 3 mm and with preovulatory follicles being, on average, 1 mm smaller. Intrafollicular estradiol and testosterone concentrations were not significantly different between the two genotypes. In contrast, L/L large follicles (>or=6 mm) had lower intrafollicular progesterone concentration. At the molecular level, expressions of ovarian markers, such as CYP19A1, CYP11A1, CYP17A1, LHR, and INHA, were not significantly different between the two genotypes. In contrast, FSHR and STAR mRNA levels increased in granulosa cells from L/L ewes. Plasma concentrations of estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and progesterone measured across a synchronized estrous cycle revealed a significant increase in estradiol levels during the follicular phase, a precocious LH surge, and an increase in progesterone level during the luteal phase of L/L ewes compared to +/+ ewes. Circulating concentrations of FSH were not different between the two genotypes. The precocious LH surge was associated with an increase in frequency of LH pulsatility during the follicular phase. At the pituitary level, mRNA levels for LHB, FSHB, GNRHR, and ESR1 were not significantly different between the two genotypes. In contrast, ESR2 mRNA expression was decreased in L/L ewes compared to +/+ ewes. Based on ovarian phenotype and endocrine profiles, these findings suggest that the mutation in the FecL gene affects ovarian function in a different way compared to other known prolific mutations affecting the bone morphogenetic protein signaling system in the ovine species.

Beta-nerve growth factor stimulates spontaneous electrical activity of in vitro embryonic mouse GnRH neurons through a P75 mediated-mechanism.

The control of ovulation helps guarantee the success of reproduction and as such, contributes to the fitness of a species. In mammals, two types of ovulation are observed: induced and spontaneous ovulation. Recent work on camelids, that are induced ovulators, highlighted the role of a factor present in seminal plasma, beta Nerve Growth Factor (ß-NGF), as the factor that triggers ovulation in a GnRH dependent manner. In the present work, we characterized alpaca ß-NGF (aß-NGF) and its 3D structure and compared it with human recombinant ß-NGF (hß-NGF). We showed that the ß-NGF enriched fraction of alpaca semen and the human recombinant protein, both stimulated spontaneous electrical activity of primary GnRH neurons derived from mouse embryonic olfactory placodes. This effect was dose-dependent and mediated by p75 receptor signaling. P75 receptors were found expressed in vitro by olfactory ensheathing cells (OEC) in close association with GnRH neurons and in vivo by tanycytes in close vicinity to GnRH fibers in adult mouse. Altogether, these results suggested that ß-NGF induced ovulation through an increase in GnRH secretion provoked by a glial dependent P75 mediated mechanism.

Modulation of estrogen receptors during development inhibits neurogenesis of precursors to GnRH-1 neurones: in vitro studies with explants of ovine olfactory placode.

The aim of the present study was to explore the putative effects of agonists and antagonists of the estradiol receptor on the early phase of GnRH-1 neuron development. To address this question we used an in vitro model of GnRH-1 neurons using cultured olfactory placode from sheep embryos on day 26 of gestation. Previous studies on this model have shown that in vitro the development of GnRH-1 neurons mimics in vivo development up to the start of pulsatile GnRH-1 secretion, To address the effects of modulating the estrogen receptor, cultures were treated with the endogenous and synthetic ligands of estradiol receptors: 17beta-estradiol, 17alpha-estradiol and tamoxifen. Neurogenesis was measured by incorporation of [(3)H]-thymidine. Morphometric parameters were evaluated by image analysis. The main results are that antagonism of estradiol receptors induced an important decrease in neurogenesis but had little effect on morphometric parameters, suggesting that during this early phase of development, maternal estrogens are important to achieve correct development of the GnRH-1 neuronal network.

Tyrosine hydroxylase expression in the olfactory/respiratory epithelium in early sheep fetuses (Ovis aries).

Transient expression of tyrosine hydroxylase (TH, the first enzyme in catecholamine synthesis) has been shown in different brain and peripheral structures of various species. TH-immunoreactive neurons have been reported in the nasal region of human and rat fetuses migrating to the forebrain with GnRH neurons during embryogenesis. In the present study, immunohistochemical analysis and in situ hybridization were performed in fetal sheep and in vitro sheep embryo olfactory placode cultures to confirm this population in this species. On embryonic days 33 to 35, TH-immunoreactive cells as well as TH cDNA-hybridized cells were found in the olfactory and respiratory epithelium and were spatially separated from GnRH-immunoreactive neurons. In days 40 to 44 of gestation, TH-immunoreactive neurons were no longer observed in the olfactory epithelium, and TH-immunoreactive fibers were found on the trajectories of the olfactory nerves. At this stage, some TH-immunoreactive fibers were also labeled for GnRH. TH-immunoreactive cells were also found in primary cultures of olfactory placodes of fetal sheep at 10 to 18 days in vitro. Some of them coexpressed GnRH. These results imply that olfactory epithelium is also able to give rise to TH expressing cells in fetal sheep, but this expression is suppressed earlier in ontogenesis than in humans due to some unidentified factors not present in the primary cultures of olfactory placode. The role of TH expression remains unclear as in other previously described examples.

Calcium channels in chicken sperm regulate motility and the acrosome reaction.

Intracellular cytoplasmic calcium ([Ca(2+) ]i ) has an important regulatory role in gamete functions. However, the biochemical components involved in Ca(2+) transport are still unknown in birds, an animal class that has lost functional sperm-specific CatSper channels. Here, we provide evidence for the presence and expression of various Ca(2+) channels in chicken sperm, including high voltage-activated channels (L and R types), the store-operated Ca(2+) channel (SOC) component Orai1, the transient receptor potential channel (TRPC1) and inositol-1,4,5-trisphosphate receptors (IP3 R1). L- and R-type channels were mainly localized in the acrosome and the midpiece, and T-type channels were not detected in chicken sperm. Orai1 was found in all compartments, but with a weak, diffuse signal in the flagellum. TRCP1 was mainly localized in the acrosome and the midpiece, but a weak diffuse signal was also observed in the nucleus and the flagellum. IP3 R1 was mainly detected in the nucleus. The L-type channel inhibitor nifedipine, the R-type channel inhibitor SNX-482 and the SOC inhibitors MRS-1845, 2-APB and YM-58483 decreased [Ca(2+) ]i sperm motility and acrosome reaction capability, with the SOC inhibitors inhibiting these functions most efficiently. Furthermore, we showed that Ca(2+) -mediated induction of AMP-activated protein kinase (AMPK) phosphorylation was blocked by SOC inhibition. Our identification of important regulators of Ca(2+) signaling in avian sperm suggests that SOCs play a predominant role in gamete function, whereas T-type channels may not be involved. In addition, Ca(2+) entry via SOCs appears to be the most likely pathway for AMPK activation and energy-requiring sperm functions such as motility and the acrosome reaction.

Ca2+/Calmodulin-Dependent Protein Kinase Kinases (CaMKKs) Effects on AMP-Activated Protein Kinase (AMPK) Regulation of Chicken Sperm Functions.

Sperm require high levels of energy to ensure motility and acrosome reaction (AR) accomplishment. The AMP-activated protein kinase (AMPK) has been demonstrated to be strongly involved in the control of these properties. We address here the question of the potential role of calcium mobilization on AMPK activation and function in chicken sperm through the Ca(2+)/calmodulin-dependent protein kinase kinases (CaMKKs) mediated pathway. The presence of CaMKKs and their substrates CaMKI and CaMKIV was evaluated by western-blotting and indirect immunofluorescence. Sperm were incubated in presence or absence of extracellular Ca(2+), or of CaMKKs inhibitor (STO-609). Phosphorylations of AMPK, CaMKI, and CaMKIV, as well as sperm functions were evaluated. We demonstrate the presence of both CaMKKs (α and ß), CaMKI and CaMKIV in chicken sperm. CaMKKα and CaMKI were localized in the acrosome, the midpiece, and at much lower fluorescence in the flagellum, whereas CaMKKß was mostly localized in the flagellum and much less in the midpiece and the acrosome. CaMKIV was only present in the flagellum. The presence of extracellular calcium induced an increase in kinases phosphorylation and sperm activity. STO-609 reduced AMPK phosphorylation in the presence of extracellular Ca(2+) but not in its absence. STO-609 did not affect CaMKIV phosphorylation but decreased CaMKI phosphorylation and this inhibition was quicker in the presence of extracellular Ca(2+) than in its absence. STO-609 efficiently inhibited sperm motility and AR, both in the presence and absence of extracellular Ca(2+). Our results show for the first time the presence of CaMKKs (α and ß) and one of its substrate, CaMKI in different subcellular compartments in germ cells, as well as the changes in the AMPK regulation pathway, sperm motility and AR related to Ca(2+) entry in sperm through the Ca(2+)/CaM/CaMKKs/CaMKI pathway. The Ca(2+)/CaMKKs/AMPK pathway is activated only under conditions of extracellular Ca(2+) entry in the cells.

Adult neurogenesis and reproductive functions in mammals.

During adulthood, the mammalian brain retains the capacity to generate new cells and new neurons in particular. It is now well established that the birth of these new neurons occurs in well-described sites: the hippocampus and the subventricular zone of the lateral ventricle, as well as in other brain regions including the hypothalamus. In this review, we describe the canonical neurogenic niches and illustrate the functional relevance of adult-born neurons of each neurogenic niche in the reproductive physiology. More specifically, we highlight the effect of reproductive social stimuli on the neurogenic processes and conversely, the contributions of adult-born neurons to the reproductive physiology and behavior. We next review the recent discovery of a novel neurogenic niche located in the hypothalamus and the median eminence and the compelling evidence of the link existing between the new-born hypothalamic neurons and the regulation of metabolism. In addition, new perspectives on the possible involvement of hypothalamic neurogenesis in the control of photoperiodic reproductive physiology in seasonal mammals are discussed. Altogether, the studies highlighted in this review demonstrate the potential role of neurogenesis in reproductive function and emphasize the importance of increasing our knowledge on the regulation processes and the physiological relevance of these adult-born neurons. This constitutes a necessary step toward a potential manipulation of these plasticity mechanisms.