Citation:

Louis, G., T. Stoker, AND D. Hallinger. IDENTIFICATION OF NEURAL BIOMARKERS OF ALTERED SEXUAL DIFFERENTIATION FOLLOWING GESTATIONAL EXPOSURE***. Presented at Socitey of Toxicology, March 10 - 14, 2013.

Impact/Purpose:

SOT poster on evaluating hypothalamic gene expression in the postnatal male rat as a measure of altered pubertal development following gestational exposure.

Description:

Sexual differentiation of the brain occurs during late gestation through the early postnatal period. The development of the phenotypical male brain is dependent on the aromatization of circulating testosterone to estradiol. Exposure to endocrine disrupting chemicals (EDCs) during early-life alters sexual maturation of the rat hypothalamic-pituitary-gonadal axis and subsequently, the timing of puberty and adult reproductive behavior. We set out to identify predictive neuronal biomarkers for use in evaluating the effect of EDCs on sexual differentiation in the male and female. We examined changes in gene expression in the rat hypothalamus [(specifically, in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC)] after in utero exposure to the aromatase inhibitor, letrozole. Pregnant dams were gavaged with vehicle or letrozole (0.1mg/kg) on gestational days 20 and 21. The AVPV and ARC were microdissected from male and female offspring on several pre-, peri-, and post-pubertal postnatal days (PND) and were evaluated for changes in expression of a number of neuropeptides that have sex specific patterns during development. These genes include those that encode for kisspeptin (Kp) and tachykinin-2 (Tac2). We identified an increase with age in the expression of Kp in the AVPV of the genetic female, but not the genetic male. Kp expression in the AVPV of the letrozole-exposed genetic male was increased to the same level observed in the genetic female on PND 14, 25 and 49. However, Kp expression in the male ARC was not altered by letrozole. ARC Tac2 expression in the male was also not changed by letrozole. This work will provide optimal time points for these measures, but additional studies are needed to determine whether these, and other CNS biomarkers, are predictive of altered puberty and/or sexual behavior due to early-life EDC exposure.

Record Details: