Puberty in beef heifers: effects of prenatal and postnatal nutrition on the development of the neuroendocrine axis

Abstract

Reproductive maturation is a complex physiological process controlled by the neuroendocrine system and is characterized by an increase in gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) pulsatile secretion. Nutrition during early development is a key factor regulating puberty onset, which is defined as first ovulation in females. In heifers, nutrient restriction after weaning delays puberty, whereas elevated levels of nutrition and energy reserves advance reproductive maturation. Recent studies in cattle and other animal models have shown that the dam's nutrition during gestation can also program the neuroendocrine system in the developing fetus and has the potential to alter timing of puberty in the offspring. Among the metabolic signals that modulate brain development and control timing of puberty is leptin, a hormone produced primarily by adipocytes that communicates energy status to the brain. Leptin acts within the arcuate nucleus of the hypothalamus to regulate GnRH secretion via an upstream network of neurons that includes neurons that express neuropeptide Y (NPY), an orexigenic peptide with inhibitory effects on GnRH secretion, and alpha melanocyte-stimulating hormone (αMSH), an anorexigenic peptide with excitatory effects on GnRH neurons. Another important population of neurons are KNDy neurons, neurons in the arcuate nucleus that co-express the neuropeptides kisspeptin, neurokinin B, and dynorphin and have strong stimulatory effects on GnRH secretion. Our studies in beef heifers indicate that increased nutrition between 4 to 8 months of age advances puberty by diminishing NPY inhibitory tone and by increasing excitatory inputs of αMSH and kisspeptin, which collectively lead to increased GnRH/LH pulsatility. Our ongoing studies indicate that different planes of nutrition during gestation can alter maternal leptin concentrations and promote changes in the fetal brain. Nonetheless, at least in Bos indicus-influenced heifers, deficits programmed prenatally can be overcome by adequate postnatal nutrition without negatively impacting age at puberty or subsequent fertility.

Keywords: heifers; hypothalamus; nutrition; puberty.

Figure 1. Nutritional and metabolic regulation of reproductive neuroendocrine function in heifers. The metabolic hormones leptin (produced primarily by adipocytes) and insulin (produced by the pancreas) act within the arcuate nucleus of the hypothalamus to modulate GnRH secretion. Since GnRH neurons do not express the receptors for these metabolic hormones, leptin and insulin must act through an upstream neuronal network. Neurons expressing proopiomelanocortin (POMC) are up-regulated by both leptin and insulin, resulting in greater synthesis and secretion of alpha melanocyte-stimulating hormone (α-MSH), which in turn stimulates kisspeptin secretion by KNDy neurons. Kisspeptin is a potent stimulator of GnRH release. Moreover, leptin and insulin suppress the expression of neuropeptide Y (NPY) within the arcuate nucleus, which has direct inhibitory effects on GnRH neurons. Therefore, the upregulation of POMC and downregulation of NPY collectively result in greater stimulation of GnRH neurons and subsequently greater GnRH/LH pulse frequency, which is a key physiological process driving puberty attainment in heifers. Created with BioRender.