OR38-6 Acute exposure to bisphenol-A (BPA) impairs typical gonadotropin releasing hormone (GnRH) and kisspeptin release in the adult female rhesus monkey hypothalamus

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR38-Physiological Impacts of Endocrine Disrupting Chemicals
Monday, June 17, 2013: 11:15 AM-12:45 PM
Presentation Start Time: 12:30 PM
Room 256 (Moscone Center)
Joseph Kurian*1, Kim L Keen2 and Ei Terasawa2
1University of Wisconsin, Madison, WI, 2Univ of Wisconsin, Madison, WI
Six billion pounds of bisphenol A (BPA) are produced throughout the world each year to manufacture polycarbonate containers, linings for metal cans and dental sealants. BPA continually leaches into our food, drinks and environment from these sources; consequently, 93% of Americans now carry biologically significant levels of this compound. Accumulating evidence suggests acute exposures to BPA may compromise adult reproductive health and success. As evidence, men with occupational exposure to BPA suffer with reduced sperm counts and quality and high blood concentrations in women are associated with repeated miscarriage. Given the latest exposure statistics and apparent acute impact of BPA on reproductive health, it is imperative that we determine the biological connections between these exposures and reproductive biology. In the present study, we investigated the acute biological impact of BPA exposure on release of two primary reproductive neuroendocrine peptides, gonadotropin releasing hormone (GnRH) and kisspeptin, in the primate hypothalamus. Using an in vivo microdialysis method in gonadal intact adult female rhesus monkeys (38-60 months of age), we found that direct infusion of BPA (10-8 and 10-9M) to the medial basal hypothalamus suppresses the release of GnRH (n=4 at each concentration). Kisspeptin release does not appear affected by these BPA infusions (n=4 at each concentration). Release of GnRH returned to baseline levels shortly after ending the infusion of BPA. To distinguish between the impact of direct and indirect BPA exposure, we also examined the effect of peripheral infusion of BPA (approximate final serum concentration: 100 ug/ml) on GnRH (n=2) and kisspeptin (n=2) release. Preliminary data suggest this route of exposure may increase baseline release of both GnRH and kisspeptin. Together, these data imply that direct exposure to BPA suppresses GnRH release, whereas indirect exposure, or serum metabolites of BPA, may have the opposite effect on GnRH and kisspeptin. As typical GnRH release patterns govern gamete maturation, ovulation, steroid hormone secretion and maintenance of luteal function, disruption of GnRH release has tremendous consequences on reproductive physiology. The data in these studies indicate that acute BPA exposure can disrupt GnRH or kisspeptin release, and consequently may have an impact on adult reproductive function as either suppression or elevation of GnRH release is a primary cause of reproductive disorders.

Nothing to Disclose: JK, KLK, ET

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: NIH K99 ES020878NIH R01 HD11355P51OD011106 / P51RR000167
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