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Transcriptional profile of the male and female rate hypothalamus during sexual differentiation
Citation:
FRAITES, M. P., A. R. BUCKALEW, AND R. L. COOPER. Transcriptional profile of the male and female rate hypothalamus during sexual differentiation. Presented at Society for Neuroscience 2009 Annual Meeting, Chicago, IL, October 17 - 21, 2009.
Impact/Purpose:
This work is the first study to fully characterize the transcriptional profile of the male and female rat hypothalamus during and after the critical perinatal period of sexual differentiation. This comprehensieve microarray data set will be used to identify marker genes and pathways important for sexual differentiation of the brain that will later help characterize the disruption of this process by environmental chemicals.
Description:
Sexual differentiation, specifically masculinization, of the hypothalamus is proposed to involve a seriesofeventsthat includethearomatization oftestosteronetoestradiol inthebrainattheend ofgestationandtheday ofbirth. Thishormonethenactivatesthetranscription ofestrogen¬responsive genes. These early organizational effects ofthe hypothalamus are critical for normal adult reproductive functioning. The objective ofthis study was to determine the transcriptional profileofthehypothalamusduringthiscritical period ofsexualdifferentiationinmaleand female rats. Determining differential gene expression ofthe hypothalamus during this early postnatal period will lay the ground work for future studies aimed at defining the effects of environmental agents on this important neuroendocrine process. Hypothalami were collected from Sprague-Dawley male and female rats at postnatal day (PND) 0 (birth) through PND 5. Total RNA was isolated and quantified from five animals in each gender/age group and samples were run on the Affymetrix GeneChip® Rat Genome 230 2.0 Array. Data normalization (RMA) and statistical analyses were done using Rosetta Resolver. Initial pathway analyses using Ingenuity software revealed significant involvement ofcell death pathways soon after birth. In addition, genes regulated by beta-estradiol and affecting amino acid metabolism and small molecule biochemistry were upregulated in male fetuses on PND 1. Interestingly, gene expression involved with thyroid hormone signaling such as deiodinase 3, thyroid hormone receptor beta, and thyroid transcription factor 1 were upregulated in female rats during the early postnatal days. By postnatal days 4 and 5, significantly activated pathways transitioned from apoptosis to cellular organization, growth, and nervous system development. Continued identification ofsex-specific marker genes and functional pathways from this data set will provide the basis for future in vivo and in vitro studies examining the effects ofenvironmental chemicals on sexual differentiation and subsequent reproductive development. This abstract, does not necessarily reflect EPA policy.