Environmental Factor, March 2009, National Institute of Environmental Health Sciences
Endocrine Disrupting Effects of BPA on Puberty and Estrogen Cycles
By Negin Martin
On February 18, Sigma Xi hosted a lunchtime talk by NIEHS grantee (http://tools.niehs.nih.gov/portfolio/sc/detail.cfm?appl_id=7462313) Heather Patisaul, Ph.D., on her latest findings about the effects on brain and ovarian function of developmental exposure to Bisphenol-A (BPA). Patisaul, an assistant professor in the department of Biology of North Carolina State University, was a recipient of a 2007 Outstanding New Environmental Scientist (ONES) award from NIEHS.
Patisau's research (http://www4.ncsu.edu/~hbpatisa/) combines approaches from behavioral biology, neuroendocrinology and molecular biology to study the effects of various environmental toxins on physiological function, focusing on how endocrine disruptors affect female reproductive physiology. Positive correlation between the increasing rates of early puberty and infertility in Western women and the rising levels of circulating BPA, which mimics estrogen, prompted her to investigate the effect of exposure to the compound on the reproductive system. Patisaul's phytoestrogen data (http://www.ncbi.nlm.nih.gov/pubmed/18656497?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum) was published in the journal Neurotoxicology; her Bisphenol data is currently in review.
BPA is a chemical commonly incorporated in polycarbonate plastics and epoxy resin used to make products such as baby and water bottles, tubing and medical devices, sports equipment, household electronics, plastic toys, lining of cans, and milk and juice cartons. According to Patisaul, BPA resembles mammalian estrogen and thyroid hormone and is suspected of being hazardous to human health. Patisaul explained that the Centers for Disease Control (CDC) estimates that the widespread use of BPA in everyday household products for the last 50 years has led to detectable levels of BPA in 95% of Americans - with levels of circulating BPA in newborns and small children under two years of age predicted to be as much as 11 times higher than adults.
Patisaul used rats as a model system to investigate whether neonatal exposure to BPA can lead to advanced puberty and possible infertility. She exposed neonatal rats briefly to the 50 micrograms /kilogram (kg) per day dose of BPA considered safe by the Food and Drug Administration (FDA) and a higher dose of 50 milligrams/kg/day. Rats treated with the low doses of BPA showed signs of early puberty similar to rats exposed to excessive estrogen. Moreover, the BPA exposed rats had irregular cycles that ended with premature infertility.
Estrogen and chemicals that mimic its structure can exert their effect on the brain by controlling hormonal secretion. In her study, Patisaul compared the function of hypothalamic neurons in the brains of BPA-treated rats and untreated rats. Specialized neurons in hypothalamus, she explained, are responsible for the secretion of gonadotropin-releasing hormone (GnRH). GnRH stimulates the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Hypothalamic neurons of the BPA-treated rats functioned normally and hence their ability to trigger secretion of hormones responsible for maintaining menstrual cycle was unchanged.
However, a closer look at the ovaries of the BPA rats revealed marked alterations in ovarian morphology and malformed follicles. Patisaul summarized her findings by stating "short, low dose, physiologically relevant levels of exposure to BPA during very early stages of development - neonatal period in rats and gestational period around the second trimester in humans - can result in advanced puberty and the impaired ability to maintain regular estrogen cycles into adulthood."
Patisaul concluded her talk by revisiting government policies regarding BPA. She emphasized the need to investigate further the effects of BPA on human health. The FDA policy of "no action required" and the established safe dose of 50 micrograms/kg/day of BPA came under criticism by the audience.
(Negin Martin, Ph.D., is a research fellow in the NIEHS Membrane Signaling Group. She was recently chosen as a 2009 Science Communication Fellow with Environmental Health Sciences.)