Our overall hypothesis is that estrogens are regulators of expressions of the genes encoding for Mtillerian inhibiting substance (MIS) and the transcription factors, SF-1, GATA-1, GATA-4, GATA-6, and DAX-1. Specifically, we hypothesize that abnormal perinatal exposure to the mammalian estrogen, 17beta-estradiol (E2), will alter the expressions of these genes during gonadogenesis and cause aberrations in gonadal structure and function. Accordingly, we propose the following three Specific Aims.
SPECIFIC AIM A: Perinatal treatment of rats with E2 will alter the expressions of the MIS, SF-1, members of the GATA family, and DAX-1 genes in the fetal and/or postnatal gonads of both sexes.
SPECIFIC AIM B: Perinatal treatment of rats with E2 will alter testicular structure, increase the proliferation of Sertoli and Leydig cells, and decrease the function of Sertoli and Leydig cells.
SPECIFIC AIM C: Perinatal treatment of rats with E2 will alter ovarian morphology and decrease ovarian steroidogenic capacity. We shall use a variety of state-of-the-art molecular biology techniques, including in situ hybridization, RNase protection assays, and reverse transcriptase-polymerase chain reaction assays. We also shall employ immunohistochemistry of the gonads, short-term cell culture techniques of the gonadal cells, and radioimmunoassays. Our results will advance significantly our understanding of the genetic mechanisms governing normal sex differentiation. Further, they will help us to elucidate the cellular and molecular mechanisms responsible for the deleterious effects of perinatal exposure to estrogens on the development of human and animal reproductive systems.

National Institute of Health (NIH)
National Institute on Minority Health and Health Disparities (NIMHD)
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Benedict College
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Blake, Charles A; McCoy, George L; Hui, Yvonne Y et al. (2011) Perinatal exposure to low-dose DE-71 increases serum thyroid hormones and gonadal osteopontin gene expression. Exp Biol Med (Maywood) 236:445-55
Nagdas, Subir K; Hamilton, Shatasha L; Raychoudhury, Samirsubas (2010) Identification of acrosomal matrix-specific hydrolases binding proteins of bovine cauda epididymal spermatozoa. J Androl 31:177-87
Hui, Yvonne Y; Lavoie, Holly A (2008) GATA4 reduction enhances 3',5'-cyclic adenosine 5'-monophosphate-stimulated steroidogenic acute regulatory protein messenger ribonucleic acid and progesterone production in luteinized porcine granulosa cells. Endocrinology 149:5557-67
Benoit, Allison M; LaVoie, Holly A; McCoy, George L et al. (2007) Expression of sperm protein 22 (SP22) in the rat ovary during different reproductive states. Exp Biol Med (Maywood) 232:910-20
Oliver, Rush H; Albury, Acchia N J; Mousseau, Timothy A (2007) Programmed cell death in flight muscle histolysis of the house cricket. J Insect Physiol 53:30-9
Gillio-Meina, Carolina; Hui, Yvonne Y; LaVoie, Holly A (2005) Expression of CCAAT/enhancer binding proteins alpha and beta in the porcine ovary and regulation in primary cultures of granulosa cells. Biol Reprod 72:1194-204
Blake, Charles A; Helmke, Steve M (2005) Proteomics of the anterior pituitary gland as a model for studying the physiology of a heterogeneous organ. Exp Biol Med (Maywood) 230:793-9
Blake, Charles A; Kakhniashvili, David G; Goodman, Steven R (2005) Mouse anterior pituitary gland: analysis by ion trap mass spectrometry. Neuroendocrinology 81:229-43
Blake, Charles A; Brown, Lewis M; Duncan, Mark W et al. (2005) Estrogen regulation of the rat anterior pituitary gland proteome. Exp Biol Med (Maywood) 230:800-7
Benoit, Allison M; McCoy, George L; Blake, Charles A (2005) Localization of fertility factor SP22 to specific cell types within the anterior pituitary gland. Exp Biol Med (Maywood) 230:721-30

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