Pineal-dependent increase of hypothalamic neurogenesis contributes to the timing of seasonal reproduction in sheep

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.

A unifying hypothesis for control of body weight and reproduction in seasonally breeding mammals

“…Importantly, a recent study has shown that hypothalamic cell proliferation is dependent on melatonin in sheep. 91 Recent studies suggest other interesting markers, such as Prss56, maybe useful in studying cell proliferation in seasonal animals. 92 Taken together, these data indicate that increased cell proliferation is another common response to short photoperiod in both long-and short-day breeders ( Table 1).…”

“…22 also include a previously unrecognised role for inflammatory signals in the healthy brain. Findings in sheep, hamster and F344 rats point to a potential photoperiodic shift in cell proliferation/neurogenesis 50,88,89,91 and this has the potential to explain the striking variation in seasonal phenotype among photoperiodic species. It is proposed that seasonal changes in physiology are related to a changing proportion of specific neurones, which results in a response across the season.…”

“…91 Recent studies suggest other interesting markers, such as Prss56, maybe useful in studying cell proliferation in seasonal animals. Importantly, a recent study has shown that hypothalamic cell proliferation is dependent on melatonin in sheep.…”

“…Hamster Male Syrian (golden) hamster Long-day breeder BrdU labelling increases after transition from long to short days 87 Male Siberian hamster Long-day breeder Nestin expression is down-regulated under short days 52,66 Sheep Male Soay sheep Short-day breeder Increased number of BrdU labelled cells under short days compared to long days 89 Ile-de France ewes Short-day breeder BrdU labelling is higher under short days 91 Increased rate of DCX-expressing neurones under short days 106 Pinealectomy affects cell proliferation; DCX-labelling is decreased after Ara-C administration 91 Photoperiod and thyroid hormone regulates Dct, a tanycyte marker implicated in neural progenitor cell proliferation 90 Rat…”

An integrative view of mammalian seasonal neuroendocrinology

“…Recent evidence obtained in sheep, using infusion of the anti‐mitotic compound Ara‐C at the bottom of the 3V, hints at a functional role for tanycytic cell proliferation in the timing of the breeding season . How cell proliferation may impact seasonal timing remains unknown .…”