Department of Animal Science, Texas A&M University, College Station, TX, USA.
Department of Animal Science, Texas A&M University, College Station, TX, USA.
Domest Anim Endocrinol. 2020 Oct;73:106434. doi: 10.1016/j.domaniend.2020.106434. Epub 2020 Jan 10.
Puberty is a complex biological event that requires maturation of the reproductive neuroendocrine axis and subsequent initiation of high-frequency, episodic release of GnRH and LH. Nutrition is a critical factor affecting the neuroendocrine control of puberty. Although nutrient restriction during juvenile development delays puberty, elevated rates of body weight gain during this period facilitate pubertal maturation by programming hypothalamic centers that underlie the pubertal process. Recent findings suggest that maternal nutrition during gestation can also modulate the development of the fetal neuroendocrine axis, thus influencing puberty and subsequent reproductive function. Among the several metabolic signals, leptin plays a critical role in conveying metabolic information to the brain and, consequently, controlling puberty. The effects of leptin on GnRH secretion are mediated via an upstream neuronal network because GnRH neurons do not express the leptin receptor. Two neuronal populations located in the arcuate nucleus that express the orexigenic peptide neuropeptide Y (NPY), and the anorexigenic peptide alpha melanocyte-stimulating hormone (αMSH), are key components of the neurocircuitry that conveys inhibitory (NPY) and excitatory (αMSH) inputs to GnRH neurons. In addition, neurons in the arcuate nucleus that coexpress kisspeptin, neurokinin B, and dynorphin (termed KNDy neurons) are also involved in the metabolic control of puberty. Our studies in the bovine female demonstrate that increased planes of nutrition during juvenile development lead to organizational and functional changes in hypothalamic pathways comprising NPY, proopiomelanocortin (POMC, the precursor of αMSH), and kisspeptin neurons. Changes include alterations in the abundance of NPY, POMC, and Kiss1 mRNA and in plasticity of the neuronal projections to GnRH neurons. Our studies also indicate that epigenetic mechanisms, such as modifications in the DNA methylation pattern, are involved in this process. Finally, our most recent data demonstrate that maternal nutrition during gestation can also induce morphological and functional changes in the hypothalamic NPY system in the heifer offspring that are likely to persist long after birth. These organizational changes occurring during fetal development have the potential to not only impact puberty but also influence reproductive performance throughout adulthood in the bovine female.
青春期是一个复杂的生物学事件，需要生殖神经内分泌轴的成熟，并随后开始 GnRH 和 LH 的高频、间歇性释放。营养是影响青春期神经内分泌控制的关键因素。虽然在青少年发育期间限制营养会延迟青春期，但在此期间体重增加率升高会通过编程下丘脑中心来促进青春期成熟，这些中心是青春期过程的基础。最近的研究结果表明，妊娠期间的母体营养也可以调节胎儿神经内分泌轴的发育，从而影响青春期和随后的生殖功能。在几种代谢信号中，瘦素在向大脑传递代谢信息方面起着至关重要的作用，从而控制青春期。瘦素对 GnRH 分泌的影响是通过一个上游神经元网络介导的，因为 GnRH 神经元不表达瘦素受体。两个位于弓状核中表达食欲肽神经肽 Y (NPY) 和厌食肽 α黑色素细胞刺激素 (αMSH) 的神经元群体，是将抑制性 (NPY) 和兴奋性 (αMSH) 输入传递给 GnRH 神经元的神经回路的关键组成部分。此外，弓状核中共同表达 kisspeptin、神经激肽 B 和强啡肽 (称为 KNDy 神经元) 的神经元也参与了青春期的代谢控制。我们在牛雌性中的研究表明，在青少年发育期间增加营养水平会导致包括 NPY、前阿黑皮素原 (POMC，αMSH 的前体) 和 kisspeptin 神经元在内的下丘脑通路的组织和功能变化。变化包括 NPY、POMC 和 Kiss1 mRNA 的丰度改变以及对 GnRH 神经元的神经元投射的可塑性改变。我们的研究还表明，表观遗传机制，如 DNA 甲基化模式的修饰，参与了这一过程。最后，我们最近的数据表明，妊娠期间的母体营养也可以诱导牛犊后代下丘脑 NPY 系统的形态和功能变化，这些变化很可能在出生后很久仍然存在。这些在胎儿发育过程中发生的组织变化不仅有可能影响青春期，而且有可能影响牛雌性整个成年期的生殖性能。
