Abstract
SummaryUndernutrition impairs reproductive success through suppression of gonadotropin-releasing hormone (GnRH), and subsequently luteinizing hormone (LH), secretion. Given that kisspeptin and neurokinin B (NKB) neurons in the arcuate nucleus (ARC) of the hypothalamus are thought to play key stimulatory roles in the generation of GnRH/LH pulses, we hypothesized that feed restriction would reduce the ARC mRNA abundance and protein expression of kisspeptin and NKB in young, male sheep. Fourteen wethers (castrated male sheep five months of age) were either fed to maintain (FM; n = 6) pre-study body weight or feed-restricted (FR; n = 8) to lose 20% of pre-study body weight over 13 weeks. Throughout the study, weekly blood samples were collected and assessed for LH concentration using RIA. At Week 13 of the experiment, animals were killed, heads were perfused with 4% paraformaldehyde, and brain tissue containing the hypothalamus was collected, sectioned, and processed for detection of mRNA (RNAscope) and protein (immunohistochemistry) for kisspeptin and NKB. Mean LH was significantly lower and LH inter-pulse interval was significantly higher in FR wethers compared to FM wethers at the end of the experiment (Week 13). RNAscope analysis revealed significantly fewer cells expressing mRNA for kisspeptin and NKB in FR wethers compared to FM controls, and immunohistochemical analysis revealed significantly fewer immunopositive kisspeptin and NKB cells in FR wethers compared to FM wethers. Taken together, this data supports the idea that long-term feed restriction regulates GnRH/LH secretion through central suppression of kisspeptin and NKB in male sheep.Lay summaryWhile undernutrition is known to impair reproduction at the level of the brain, the components responsible for this in the brain remain to be fully understood. Using male sheep we examined the effect of undernutrition on two stimulatory molecules in the brain critical for reproduction: kisspeptin and neurokinin B. Feed restriction for several weeks resulted in decreased luteinizing hormone in the blood indicating reproductive function was suppressed. In addition, undernutrition also reduced both kisspeptin and neurokinin B levels within a region of the brain involved in reproduction, the hypothalamus. Given that they have stimulatory roles in reproduction, we believe that undernutrition acts in the brain to reduce kisspeptin and neurokinin B levels leading to the reduction in luteinizing hormone secretion. In summary, long-term undernutrition inhibits reproductive function in sheep through suppression of kisspeptin and neurokinin B within the brain.
Highlights
The capacity for reproduction first occurs at puberty and is the result of an activated hypothalamic– pituitary–gonadal axis
As a critical window of time in physiological development, puberty onset is heralded at the neuroendocrine level by an elevation of pulsatile gonadotropin-releasing hormone (GnRH) secretion from the CNS, which in turn elicits an increase of luteinizing hormone (LH) secretion from the anterior pituitary
Since kisspeptin neurons in the arcuate nucleus (ARC) of the hypothalamus highly express neurokinin 3 receptor (NK3R), while GnRH neurons appear to be devoid of NK3R (Amstalden et al 2010, Ahn et al 2015), neurokinin B (NKB) action is thought to occur through stimulation of ARC kisspeptin which in turn stimulates GnRH neurons
Summary
The capacity for reproduction first occurs at puberty and is the result of an activated hypothalamic– pituitary–gonadal axis. Mutations in the genes encoding the neuropeptide kisspeptin or its receptor, Kiss1R ( known as G-protein coupled receptor 54, GPR54) result in impairment of pubertal maturation and reproductive function in humans and mice (de Roux et al 2003, Seminara et al 2003, Topaloglu et al 2012), which is compelling evidence that kisspeptin is an essential component of normal pubertal development and fertility. Neurokinin B (NKB) is essential for puberty, as loss-of-function mutations in the genes encoding NKB or its receptor, neurokinin 3 receptor (NK3R), result in failure of pubertal progression and infertility in humans (Topaloglu et al 2009). Work in rodents has shown that removal of Kiss1R signaling abrogates the response to senktide (Garcia-Galiano et al 2012, Grachev et al 2012b) and demonstrates that NKB signaling is upstream of kisspeptin signaling
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
