In vivoandin vitrobisphenol A exposure effects on adiposity

Abstract

In utero exposure to the ubiquitous plasticizer, bisphenol A (BPA) is associated with offspring obesity. As adipogenesis is a critical factor contributing to obesity, we determined the effects of in vivo maternal BPA and in vitro BPA exposure on newborn adipose tissue at the stem-cell level. For in vivo studies, female rats received BPA before and during pregnancy and lactation via drinking water, and offspring were studied for measures of adiposity signals. For in vitro BPA exposure, primary pre-adipocyte cell cultures from healthy newborns were utilized. We studied pre-adipocyte proliferative and differentiation effects of BPA and explored putative signal factors which partly explain adipose responses and underlying epigenetic mechanisms mediated by BPA. Maternal BPA-induced offspring adiposity, hypertrophic adipocytes and increased adipose tissue protein expression of pro-adipogenic and lipogenic factors. Consistent with in vivo data, in vitro BPA exposure induced a dose-dependent increase in pre-adipocyte proliferation and increased adipocyte lipid content. In vivo and in vitro BPA exposure promotes the proliferation and differentiation of adipocytes, contributing to an enhanced capacity for lipid storage. These findings reinforce the marked effects of BPA on adipogenesis and highlight the susceptibility of stem-cell populations during early life with long-term consequence on metabolic homeostasis.

Impact of gestational low protein diet and postnatal bisphenol A exposure on chemically induced mammary carcinogenesis in female offspring rats

“…However, when these pups are exposed to NPD or to an overnutrition occur a greater ability to efficiently store nutrients that results in obesity later in life . Thus, the findings associated to the increase in the fad pad content observed in the mammary gland from LPD + BPA animals by histology analysis can be due to a compensatory response to IGR associated with postnatal BPA exposure, since BPA have been shown to activate PPAR‐gamma and induce adipogenesis …”

“…[40][41][42] Thus, the findings associated to the increase in the fad pad content observed in the mammary gland from LPD + BPA animals by histology analysis can be due to a compensatory response to IGR associated with postnatal BPA exposure, since BPA have been shown to activate PPAR-gamma and induce adipogenesis. 43,44 Estrogen and progesterone are major steroid hormones associated with cell proliferation and death and cellular differentiation in normal mammary gland. 31 In special, progesterone hormone particularly regulates tertiary side branching of epithelial ducts following ductal morphogenesis.…”

Bisphenol A and Phthalates in Diet: An Emerging Link with Pregnancy Complications

“…Indeed, adipocyte hypertrophy occurred in the progeny of rats that received BPA during pregnancy, along with a rise in the expression of pro-adipogenic factors. Proliferation of pre-adipocyte induced by BPA has been described in vitro as well [109,110,130]. In cultures of 3T3-L1 pre-adipocytes, the expression of PPARγ was enhanced by BPA, and lipid content in mature cells increased.…”

The Case for BPA as an Obesogen: Contributors to the Controversy

“…A recent study by Desai et al (42), reported significant increases in BW and fat mass at 3 and 24 weeks of age in male but not female Sprague Dawley rats born to mothers exposed to BPA in their drinking water from 2 weeks prior to mating through pregnancy and lactation (5 mg BPA/liter which provided 500–900 μg/kg BW/day during pregnancy and ~1500 μg/kg BW/day during lactation). Further study of the BPA exposed males at 3 weeks of age revealed an increase in adipocyte size, lipogenic factors (SrebP1 and C/EBP alpha), and inflammation in the retroperitoneal fat pad.…”