Bisphenol A (BPA) induces progesterone receptor expression in an estrogen receptor α-dependent manner in perinatal brain

• Published in: Neurotoxicology and teratology 2020-03, Vol.78, p.106864-106864, Article 106864
• Main Authors: Fahrenkopf, Allyssa, Wagner, Christine K.
• Format: Article
• Language: English
• Subjects: Animals; Benzhydryl Compounds - toxicity; Bisphenol A; Development; Estrogen receptor; Estrogen Receptor alpha - biosynthesis; Estrogens, Non-Steroidal - toxicity; Female; Phenols - toxicity; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Preoptic Area - drug effects; Preoptic Area - metabolism; Progesterone receptor; Rats, Sprague-Dawley; Receptors, Progesterone - biosynthesis
• ISSN: 0892-0362; 1872-9738
• DOI: 10.1016/j.ntt.2020.106864

Bisphenol A (BPA) is a xenoestrogen that is prevalent in the environment of industrialized nations due its use in the production of many plastic household items. Virtually all adults in the U.S. have detectable levels of BPA in urine and it can be measured in fetal serum and in breastmilk, making developmental exposure a particular concern. The present study utilizes a progesterone receptor (PR) expression bioassay to assess the estrogen receptor α (ERα)-dependent effects of BPA in fetal rodent brain following maternal exposure. Maternal ingestion of 10 μg/kg/day, but not 50 μg/kg/day, BPA from gestational day 14–22 significantly increased levels of PR immunoreactivity (PRir) in the medial preoptic nucleus (MPN) of female offspring. PR expression in the perinatal MPN is highly dependent on the activation of ERα, but not ERβ, by estrogens. Indeed, injections of BPA (5 μg/kg) to neonates from postnatal day 2–4 (P2–4) significantly increased PR expression in the MPN of postnatal day 5 females compared to the MPN of females administered the oil vehicle. However, pretreatment with the ER antagonist, ICI 182,780 from P1–4 significantly attenuated the effects of BPA on PR expression, indicating an ERα-dependent mechanism. The present results also demonstrate a non-monotonic effect of BPA on the direct expression of a transcription factor in developing brain. •Maternal ingestion of BPA induces progesterone receptor the MPN of female neonates.•Induction of PR by BPA is attenuated by ERα antagonist.•Maternal BPA exerts estrogenic effects in fetal brain via ERα.•PR expression in fetal brain is a novel biomarker for estrogenic activity of BPA.