Abstract

To survive in temperate latitudes, species rely on the photoperiod to synchronize their physiological functions, including reproduction, with the predictable changes in the environment. In sheep, exposure to decreasing day length reactivates the hypothalamo-pituitary-gonadal axis, while during increasing day length, animals enter a period of sexual rest. Neural stem cells have been detected in the sheep hypothalamus and hypothalamic neurogenesis was found to respond to the photoperiod. However, the physiological relevance of this seasonal adult neurogenesis is still unexplored. This longitudinal study, therefore aimed to thoroughly characterize photoperiod-stimulated neurogenesis and to investigate whether the hypothalamic adult born-cells were involved in the seasonal timing of reproduction. Results showed that time course of cell proliferation reached a peak in the middle of the period of sexual activity, corresponding to decreasing day length period. This enhancement was suppressed when animals were deprived of seasonal time cues by pinealectomy, suggesting a role of melatonin in the seasonal regulation of cell proliferation. Furthermore, when the mitotic blocker cytosine-b-D-arabinofuranoside was administered centrally, the timing of seasonal reproduction was affected. Overall, our findings link the cyclic increase in hypothalamic neurogenesis to seasonal reproduction and suggest that photoperiod-regulated hypothalamic neurogenesis plays a substantial role in seasonal reproductive physiology.

Highlights

  • In order to cope with the harsh annual changes of their environment, species living in temperate and arctic latitudes use a strategy relying on annual changes in day length or photoperiod to synchronize their physiological functions including reproduction with the constraints of external climatic and food availability[1]

  • At the end of the experiment there were significantly fewer DCX-positive cells in Ara-C treated animals than in controls (Fig. 4g and h, 43.6 ± 7.3 DCX + cells per mm[2] and 16.9 ± 3.6 DCX + cells per mm[2], respectively p < 0.01). This longitudinal study highlighted an increase in hypothalamic cell proliferation occurring as a single peak during the middle of the sexual activity period (SP) and demonstrated that this enhancement was pineal dependent

  • Cell proliferation in the sub-granular zone (SGZ) was found to be dependent of the time of the year and was affected by pinealectomy

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Summary

Introduction

In order to cope with the harsh annual changes of their environment, species living in temperate and arctic latitudes use a strategy relying on annual changes in day length or photoperiod to synchronize their physiological functions including reproduction with the constraints of external climatic and food availability[1]. Adult neurogenesis is a plasticity mechanism conserved throughout the animal kingdom It relies on the existence of mitotically active neural stem cells (NSCs) located within highly specialized microenvironments called neurogenic niches. The number of dividing hypothalamic cells increased in December compared to July[17], and this was independent of the ovarian steroid feedback[17] This enhanced cell proliferation was shown to be linked to a robust increase in neurogenesis during decreasing day length demonstrated through immunohistochemical detection of doublecortin (DCX), a marker of newborn neurons[11,16,18]. These studies only evaluated proliferation at two time points in the year. We provided evidence that adult hypothalamic neurogenesis was linked functionally to the seasonal timing of reproduction

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