Perinatal Exposure to Low Doses of Bisphenol A Affects Body Weight, Patterns of Estrous Cyclicity, and Plasma LH Levels

Abstract

The nonsteroidal estrogenic compound bisphenol A (BPA) is a monomer used in the manufacture of polycarbonate plastics and resins. BPA may be ingested by humans as it reportedly leaches from the lining of tin cans into foods, from dental sealants into saliva, and from polycarbonate bottles into their contents. Because BPA is weakly estrogenic-approximately 10,000-fold less potent than 17β-estradiol-current environmental exposure levels have been considered orders of magnitude below the dose required for adverse effects on health. Herein we demonstrate measurable effects on the offspring of Sprague-Dawley female rats that were exposed, via their drinking water, to approximately 0.1 mg BPA/kg body weight (bw)/day (low dose) or 1.2 mg BPA/kg bw/day (high dose) from day 6 of pregnancy through the period of lactation. Offspring exposed to BPA exhibited an increase in body weight that was apparent soon after birth and continued into adulthood. In addition, female offspring exposed perinatally to the high dose of BPA exhibited altered patterns of estrous cyclicity and decreased levels of plasma luteinizing hormone (LH) in adulthood. Administration of neither the doses of BPA that caused effects during perinatal exposure nor a 10-fold higher dose was able to evoke a uterotropic response in ovariectomized postpubertal females. These data indicate an increased sensitivity to BPA during the perinatal period and suggest the need for careful evaluation of the current levels of exposure to this compound.

Epigenetic regulation in obesity

“…78 Accordingly, also maternal high-fat feeding may prime the offspring for obesity, as exemplified by altered DNA methylation of appetite regulatory genes: Rodent offspring exposed in utero to high-fat diet had promoter hypomethylation both globally and in dopamine transporter 3 (Dat), opioid receptor (Mor) and preproenkephalin (Penk), as well as long-term alterations in behavior and preference for foods high in fat and sugar. 79 Exposure to the DNA-hypomethylating bisphenol A in utero or neonatally was associated with higher body weight, 80 but methyl donors such as folic acid or genistein in the diet prevented this effect. 81 Hence, maternal methyl group supply, such as folate and choline, a maternal low-protein diet and a maternal high-fat diet in rodents throughout pregnancy has been shown to modify DNA methylation of some metabolic genes.…”

Induction of mammary gland ductal hyperplasias and carcinoma in situ following fetal bisphenol A exposure

“…Thus, the fetuses were exposed to BPA or vehicle from E9 until postnatal day (PND) 1. A wide range of BPA doses were tested because, contrary to the mouse model, to our knowledge there are no data available on developmental effects of BPA in the mammary gland of rats, with the exception of one study on Sprague-Dawley rats exposed to 0.1 and 1.2mg BPA/kg BW/day from E5 to weaning via drinking water [29].…”

“…Exposure of rodents to low doses of BPA during fetal development has been shown to alter a variety of biological endpoints including early vaginal opening [26], early onset of puberty [27], disrupted estrous cyclicity [28,29], and decreased levels of luteinizing hormone following ovariectomy [29].…”

Bisphenol A exposure and associations with obesity among adults: a critical review

“…The majority of research on the association between BPA and weight gain to date has focused on in utero and early-life exposures. Exposure to low levels of BPA perinatally (50)(51)(52)(53)(54)(55)(56)(57)(58) , and during adolescence (59,60) , has been shown to result in increased weight in rodents. Few studies have evaluated the risk of obesity associated with BPA exposure in adult animals.…”