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Effects of Perinatal Polychlorinated Biphenyls on Adult Female Rat Reproduction: Development, Reproductive Physiology, and Second Generational Effects¹

The Institute for Neuroscience,³ Division of Pharmacology & Toxicology,⁴ College of Pharmacy, Section of Integrative Biology,⁵ and the Institute for Cell and Molecular Biology,⁶ The University of Texas at Austin, Austin, Texas 78712 Department of Biology,⁷ University of Wisconsin, Whitewater, Wisconsin 53190

ABSTRACT

Perinatal exposures to endocrine-disrupting chemicals, such as polychlorinated biphenyls (PCBs), can cause latent effects on reproductive function. Here, we tested whether PCBs administered during late pregnancy would compromise reproductive physiology in both the fetally exposed female offspring (F1 generation), as well as in their female offspring (F2 generation). Pregnant Sprague-Dawley rats were treated with the PCB mixture, Aroclor 1221 (A1221; 0, 0.1, 1, or 10 mg/kg), on Embryonic Days 16 and 18. Somatic and reproductive development of F1 and their F2 female offspring were monitored, including ages of eye opening, pubertal landmarks, and serum reproductive hormones. The results showed that low doses of A1221 given during this critical period of neuroendocrine development caused differential effects of A1221 on F1 and F2 female rats. In both generations, litter sex ratio was skewed toward females. In the F1 generation, additional effects were found, including a significant alteration of serum LH in the 1 mg/kg A1221 group. The F2 generation showed more profound alterations, particularly with respect to fluctuations in hormones and reproductive tract tissues across the estrous cycle. On proestrus, the day of the preovulatory GnRH/gonadotropin surge, F2 females whose mothers had been exposed perinatally to A1221 exhibited substantially suppressed LH and progesterone concentrations, and correspondingly smaller uterine and ovarian weights on estrus, compared with F2 descendants of control rats. These latter changes suggest a dysregulation of reproductive physiology. Thus, low levels of exposure to PCBs during late fetal development cause significant effects on the maturation and physiology of two generations of female offspring. These findings have implications for reproductive health and fertility of wildlife and humans.

Aroclor 1221, endocrine disruption, environment, estradiol, luteinizing hormone, PCBs, progesterone, reproduction, transgenerational effects

¹Supported by the PhRMA Foundation (Predoctoral Fellowship to R.M.S.) and the National Institute of Environmental Health Services (ES12272 and ES07784 to A.C.G.).

Correspondence: ²Andrea C. Gore, Division of Pharmacology & Toxicology, A1915 University of Texas at Austin, Austin, TX 78712. FAX: 512 471 5002; e-mail: andrea.gore{at}mail.utexas.edu