Effects of Prenatal Phthalate Exposure and Childhood Exercise on Maternal Behaviors in Female Rats at Postpartum: A Role of Oxtr Methylation in the Hypothalamus.

Yi-Ju Lee,Yi-Ching Lee,Dean-Chuan Wang,Muhammad Asad Chaudhary,Hwai-Ting Lin

doi:10.3390/ijms22189847

Abstract

Both the detrimental effect of prenatal exposure to di-(2-ethylhexyl)-phthalate (DEHP) and the beneficial effects of physical exercise on brain functions have been reported. The oxytocin pathway has been implicated in the onset of maternal behaviors. Epigenetic modification of the oxytocin receptor gene (OXTR) through DNA methylation has been associated with the pathogenesis of neuropsychiatric disorders. The purpose of this study was to investigate the effects of prenatal DEHP exposure on oxytocin-regulated maternal behaviors and to examine the protective effect of exercise. Pregnant rats (F0) were fed with vehicle or DEHP during gestation and the offspring females (F1) were assessed for their maternal behaviors by pup retrieval test at postpartum. The results showed that reduced pup retrieval activities without significant alteration of stress responses were observed in the prenatally DEHP-exposed females. Prenatal DEHP exposure decreased the expressions of oxytocin, Oxtr mRNA, and oxytocin receptor, and increased Oxtr methylation in the hypothalamus of postpartum female rats. There were no significant effects of exercise on behavioral, biochemical, and epigenetic measurements. These results suggest that prenatal DEHP exposure has a long-term adverse effect on maternal behaviors; Oxtr hyper-methylation may be a potential epigenetic mechanism for this alteration, which cannot be prevented by physical exercise during childhood.

Highlights

The quality of maternal care has a significant influence on the offspring’s physiological and psychological development across many mammalian species [1]
These results suggest that stress responses were not affected by either prenatal DEHP exposure or childhood exercise in postpartum dams
The study is that prenatally rats rats exhibited impaired maternal behaviors in some categories, such as longer latency exhibited impaired maternal behaviors in some categories, such as longer latency to reto retrieve thepup, first lower pup, lower number of retrieved pups, time in pup trieve the first number of retrieved pups, and lessand timeless spent in spent pup retrieval retrieval and licking

Summary

Introduction

The quality of maternal care has a significant influence on the offspring’s physiological and psychological development across many mammalian species [1]. The initiation of maternal behaviors relies on the functions of neurotransmitters and neuromodulators acting during postpartum. The neuropeptide oxytocin, produced in the hypothalamus, is implicated as a system supporting neurobehavioral adaptation during pregnancy, childbirth, and postpartum caregiving in several species [2]. Oxytocin levels are related to a set of maternal bonding behaviors, including gaze, vocalization, positive affect, affectionate touch, and frequent checking of the infant [3,4]. There is a concurrent expression of the oxytocin receptor (OTR) in the hypothalamus [8] Oxytocin administration induces maternal behaviors such as more efficient pup retrieval and pup grouping in the nest [5,6], whereas oxytocin antagonist treatment impairs maternal behaviors in postpartum rats [7].

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