Use of a Bayesian screening approach and gene ontology annotations to filter and interpret microarray data from the uteri of estrogen-treated mice.

Ahmed EI, Tang YP, Burgoon LD, Zacharewski TR, Sisk CL.

Neuroscience Program, Dept. of Pharmacology, Dept. of Biochemistry, Dept. of Psychology, Michigan State University, East Lansing, MI.

Developmental exposure to polychlorinated biphenyls (PCBs) can result in neurological and reproductive abnormalities, possibly due to interactions of PCBs with estrogen receptors. The rat hypothalamic anteroventral periventricular nucleus (AVPv) governs steroid-induced gonadotropin surges. It is larger in females than in males, who are incapable of generating gonadotropin surges. This structural and functional sexual dimorphism is the result of perinatal exposure of the male brain to estrogen. This study examined the effect of developmental exposure to the PCB mixture Aroclor 1242 on AVPv structure. Pregnant rats were gavaged daily with corn oil vehicle, 0.5, 5, or 25 mg/kg Aroclor 1242 during gestation and lactation. The male and female offspring of control and treated dams were weaned at 21d of age and brains were collected at 100-140 d. Coronal brain sections were Nissl stained, and the cross-sectional area of AVPv was determined microscopically. AVPv area was 1.5x larger in control females than in control males, as expected. AVPv area was reduced in females by all doses of PCBs, but was unaffected by PCBs in males. AVPv area of PCB-exposed females (all doses) was similar to that of control males. In contrast, PCB exposure did not affect the area of the non-sexually dimorphic anterodorsal preoptic nucleus. Thus, developmental exposure to PCBs during a critical period of neural development alters sexual differentiation of the AVPv, potentially impacting neuroendocrine function in adulthood.

Supported by ES10149.