Exposure to EP-1 during lactation on maternal behavior, offspring early development, quinestrol transfer and relative receptors in maternal and offspring of Kunming mice

Abstract

Maternal exposure to EP-1 (quinestrol: levonorgestrel = 1:2) during lactation harms the gonads and the reproduction of offspring. However, it is not clear how the mother’s exposure causes damage to the offspring, whether offspring are exposed to EP-1 through mother's milk, or how it affects the early neurodevelopment of the offspring. A control group, low-dose group, and high-dose group were administered EP-1 at 0, 3, and 5 mg/kg, respectively, and changes in maternal behaviors, hormones, relevant receptor expression in the brain and mammary glands, and quinestrol levels in blood and milk were examined. Offspring survival, body weight, hormone levels, and brain receptor expression were examined too. EP-1 exposure increased maternal behavior, serum estradiol, and oxytocin levels, but decreased prolactin. EP-1 exposure elevated estrogen receptor 1 and oxytocin receptor expression in the medial preoptic area (MPOA), ventral tegmental area (VTA), and estrogen receptor 1 in the mammary tissue, but decreased prolactin receptor expression in the MPOA, VTA, and mammary glands. Quinestrol was found in the blood and milk of maternal mice. In early pups, EP-1 exposure decreased offspring survival, body weight, testosterone, and growth hormone levels, and increased serum estradiol. EP-1 exposure decreased estrogen receptors 1 and 2 in the hypothalamus (HYP) and amygdala, and kisspeptin receptors (Kiss1R) in HYP in female offspring, but increased Kiss1R in male offspring. In conclusion, maternal EP-1 exposure during lactation increases maternal behavior and corresponding neuroendocrine hormones; quinestrol transmitted through milk and reduced milk may affect early offspring development, especially the neuroendocrine system.