Perinatal High-Fat Diet and Bisphenol A: Effects on Behavior and Gene Expression in the Medial Prefrontal Cortex

Abstract

Both high-fat diets and bisphenol A (BPA), an environmental endocrine disruptor, are prevalent in industrialized societies. Previous studies have detected separate effects of BPA and high-fat diets; however, none have assessed possible interactive effects. Here, pregnant dams consumed 0, 40 or 400 μg/kg/day BPA and were fed either a control (CON; 15.8% kcal fat) or high-fat diet (HFD; 45% kcal fat) from gestational day 2 through parturition. The pups were individually dosed with BPA from postnatal days (P) 1–10, while the dams continued to consume one of the two diets. Maternal behavior increased with the HFD while the offspring’s periadolescent social play decreased with BPA, but no interactive effects were observed. Neither HFD nor BPA exposure changed performance on a social recognition task, and only BPA had an effect on the elevated plus maze. BPA increased several cytokines in the medial prefrontal cortex (mPFC) of P10 males, but not females. Expression of several genes related to hormone synthesis and receptors, inflammation, oxidative stress, and apoptosis in the mPFC at P10 and P90 were altered due to BPA and/or HFD exposure with rare interactive effects. BPA resulted in an increase in the gene expression of Esr1 in the mPFC of females at both P10 and P90. Epigenetic analysis at P90 did not show a change in methylation or in the levels of pre-mRNA or microRNA. Thus perinatal BPA and HFD have separate effects but rarely interact.

Adult Male Rats Show Resilience to Adolescent Bisphenol A Effects on Hormonal and Behavioral Responses While Co-Exposure With Hop Extracts Supports Synergistic Actions

“…Previous studies have supported gestational and perinatal BPA exposure to exert lasting anxiogenic effects in rodents (Xu et al, 2012 ; Chen et al, 2015 ), while others have supported reduced anxiety-like behaviors (Farabollini et al, 1999 ), demasculinization of male behavior (Jones and Watson, 2012 ), or no effects (Wise et al, 2019 ). During adolescence, daily BPA dietary exposure failed to significantly affect EPM open arm time and entries in adult rats.…”

“…Similarly, although at much lower doses, prenatal and lactational BPA doses of 40 and 400 μg/kg/day in male Sprague–Dawley rats failed to affect adult play behavior (Dessì-Fulgheri et al, 2002 ). Moreover, using similar dosages, perinatal exposure in Long Evans rats failed to show lasting impact on adult social memory (Wise et al, 2019 ). Notably, using transgenerational and prenatal BPA administration regimens, Wolstenholme et al ( 2019 ) and Rebuli et al ( 2016 ) demonstrated earlier periods of development to be more sensitive to lasting effects on sociability.…”

“…In this context, upregulation of basal and stress-induced corticosterone (CORT) levels has been observed following gestational and lactational low-dose BPA exposure (40 µg/kg/day) in male rats (Panagiotidou et al, 2014) while perinatal and adult low-and high-dose exposure increased anxiety and depressive-like behavior (Matsuda et al, 2012;Chen et al, 2014;Xu et al, 2015). However, other studies have reported reduced anxiety or no effects following perinatal BPA exposure (Farabollini et al, 1999;Jones and Watson, 2012;Wise et al, 2019). Growing evidence further supports BPA-induced dysregulation of the hypothalamicpituitary-gonadal (HPG) axis, ultimately affecting estrogen (E) and testosterone (T) secretion.…”

Effects of Bisphenol A Exposure during Pregnancy and lactation on Hippocampal Function in Newborn Rats

“…The latest data of experimental studies showed that bisphenol A exposure had adverse effects on oocyte quality, sperm production and quality, testicular cells, hormone level, ovarian function and uterine morphology in animal models 20 . Studies have also shown that maternal BPA exposure during childbirth can affect offspring learning and memory ability 21 . However, the potential mechanism of Bisphenol A related to brain development still needs to be further explored.…”

Laboratory Markers in the Management of Pediatric Polytrauma: Current Role and Areas of Future Research

“…Similarly, IL-6 is considered to be a reliable prognostic biomarker for pediatric TBI ( 123 ). The administration of 20-hydroxyeicosatetraenoic acid improved the functional outcomes of rats in an experimental pediatric TBI model by decreasing the gene expression of TNF and IL-1β ( 133 ). Moreover, microglia/macrophages might also play an important role in the injury mechanisms following pediatric TBI ( 134 ).…”