Alteration of pituitary hormone-immunoreactive cell populations in rat offspring after maternal dietary exposure to endocrine-active chemicals

Abstract

We previously performed dose-response studies of genistein, diisononyl phthalate, 4-nonylphenol, methoxychlor (MXC), and bisphenol A to examine the impact of maternal dietary exposure from gestational day 15 to postnatal day 10 on the development of rat reproductive system in later life. Among the chemicals MXC alone showed typical estrogenic effects only at the maternally toxic 1200 ppm. The present study was performed to examine the sensitivity of immunohistochemical analysis of pituitary cells of offspring similarly exposed to each chemical for detection of endocrine-disrupting effects. For this purpose, ratios of pituitary cells expressing luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL), were measured at 3 and 11 weeks of age. Ethinylestradiol (EE) at 0.5 ppm was used as a reference chemical. At week 3, decrease in the relative proportions of LH, FSH, and PRL cells in males and LH cells in females was evident with MXC at 1200 ppm. At week 11, increase was found for PRL cells from 240 ppm MXC, and FSH cells at 1200 ppm in females. On the other hand, EE increased the PRL cell percentage in females at week 3 but no effects were apparent at week 11. The other chemicals were without influence at either time point. The results suggest that the assessment of the pituitary cell populations might be a more sensitive approach to detect perinatal endocrine-disrupting effects than other methods. The difference in the pituitary effect between MXC and EE is discussed.

In vivo effects of bisphenol A in laboratory rodent studies

“…The Crl:CD (SD) rat strain is insensitive to BPA, and 0 of 13 studies report low dose effects [155][156][157][158][159][160][161][162][163][164][165][166][167]. In addition, this rat strain is insensitive to the drug ethinylestradiol at doses (~0.5 μg/kg/day) used in oral contraceptives [163,167]. As shown above, a large number of studies show that significant low-dose effects of BPA have been observed in the original Sprague-Dawley rat.…”

NTP‐CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A

“…Experiment 2 is inadequate for consideration due to inappropriate statistics that failed to account for litter effects. Masutomi et al (2004), supported by the Japanese Ministry of Health, Labour, and Welfare, examined the potential effects in rats of neonatal bisphenol A exposure through maternal dietary intake on the number of offspring pituitary cells positive for LH, FSH, and prolactin. The authors exposed 5-8 pregnant CD(SG)IGS dams from GD 15-PND 10 to soy-free diet containing: (1) genistein 20, 200, or 1000 ppm; (2) diisononyl phthalate 400, 4000, or 20,000 ppm; (3) methoxyclor 24, 240, or 1200 ppm; (4) 4-nonylphenol 60, 600, or 3000 ppm; or (5) bisphenol A [96.5% purity] 60, 600, or 3000 ppm.…”

Epigenetic effects of endocrine-disrupting chemicals on female reproduction: An ovarian perspective

“…Although some studies show that treatment with MXC alters GnRH mRNA levels in the POA in adult female rats [208], oral exposure to 1200 ppm MXC during fetal and neonatal periods, did not affect the size of the SDN-POA in the hypothalamus [209]. In contrast, similar oral developmental exposure caused an increase in PR in the POA of adult female rats [210] and altered the number of gonadotropes and lactotropes in the pituitary [211]. More recently, it was shown that MXC exposure during fetal and neonatal periods altered ERα gene expression in the POA in aged (17–18 months) female rats [212].…”