Cardoso Rodolfo C, Alves Bruna R C, Williams Gary L
Texas A&M University, College Station, TX, USA.
University of Nevada, Reno, NV,USA.
Anim Reprod. 2018 Aug 3;15(Suppl 1):868-878. doi: 10.21451/1984-3143-AR2018-0013. eCollection 2018 Jul-Sep.
Puberty is a complex physiological process in females that requires maturation of the reproductive neuroendocrine system and subsequent initiation of high- frequency, episodic release of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH). Genetics and nutrition are two major factors controlling the timing of puberty in heifers. While nutrient restriction during the juvenile period delays puberty, accelerated rates of body weight gain during this period have been shown to facilitate pubertal development by programming hypothalamic centers that underlie the pubertal process. Among the different metabolic factors, leptin plays a critical role in conveying nutritional information to the neuroendocrine axis and controlling pubertal progression. Because GnRH neurons are devoid of the leptin receptor, leptin's effects on GnRH neurons must be relayed via an afferent neuronal network. Two neuronal populations located in the arcuate nucleus (ARC) that express the orexigenic peptide neuropeptide Y (NPY), and the anorexigenic peptide alpha melanocyte-stimulating hormone (αMSH), are key components of afferent pathways that convey inhibitory (NPY) and excitatory (αMSH) inputs to GnRH neurons. In addition, ARC neurons expressing kisspeptin, a potent stimulator of GnRH release, are also involved in the nutritional regulation of puberty. Our studies have demonstrated that increased planes of nutrition during juvenile development result in morphological and functional changes in hypothalamic pathways comprising NPY, proopiomelanocortin (POMC), and kisspeptin neurons. Changes included differential expression of NPY, POMC, and Kiss1 in the ARC, and plasticity in the axonal projections to GnRH and kisspeptin neurons. Additionally, increased rates of body weight gain also promoted changes in the pattern of DNA methylation, a key epigenetic mechanism for regulation of gene expression. Finally, our most recent findings suggest that maternal nutrition during gestation can also induce structural and functional changes in hypothalamic neurocircuitries that are likely to persist long after pubertal maturation and influence reproductive performance throughout adulthood in cattle.
青春期是女性复杂的生理过程，需要生殖神经内分泌系统成熟，随后启动促性腺激素释放激素（GnRH）和促黄体生成素（LH）的高频、间歇性释放。遗传和营养是控制小母牛青春期时间的两个主要因素。幼年期营养限制会延迟青春期，而在此期间体重加速增加已被证明可通过对青春期过程基础的下丘脑中心进行编程来促进青春期发育。在不同的代谢因素中，瘦素在将营养信息传递至神经内分泌轴以及控制青春期进程方面起着关键作用。由于GnRH神经元缺乏瘦素受体，瘦素对GnRH神经元的作用必须通过传入神经网络来传递。位于弓状核（ARC）的两个神经元群体，即表达促食欲肽神经肽Y（NPY）和促食欲肽α黑素细胞刺激激素（αMSH）的群体，是将抑制性（NPY）和兴奋性（αMSH）输入传递至GnRH神经元的传入通路的关键组成部分。此外，表达Kisspeptin（GnRH释放的强效刺激物）的ARC神经元也参与青春期的营养调节。我们的研究表明，幼年期发育期间营养水平的提高会导致包含NPY、阿片-促黑素细胞皮质素原（POMC）和Kisspeptin神经元的下丘脑通路发生形态和功能变化。变化包括ARC中NPY、POMC和Kiss1的差异表达，以及向GnRH和Kisspeptin神经元的轴突投射的可塑性。此外，体重增加率的提高还促进了DNA甲基化模式的变化，DNA甲基化是调节基因表达的关键表观遗传机制。最后，我们最近的研究结果表明，妊娠期间的母体营养也可诱导下丘脑神经回路发生结构和功能变化，这些变化可能在青春期成熟后长期持续，并影响牛成年后的繁殖性能。
