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Gestational and Lactational Exposure of Male Mice to Diethylstilbestrol Causes Long-Term Effects on the Testis, Sperm Fertilizing Ability in Vitro, and Testicular Gene Expression

Department of Biochemistry and Molecular Biology, National Food Safety and Toxicology Center (M.R.F., R.G.H., C.J.F., T.R.Z.), and Department of Animal Science (K.C.), Institute for Environmental Toxicology, Michigan State University, East Lansing, Michigan 48824; and Department of Veterinary Anatomy and Public Health, Texas A&M University College of Veterinary Medicine (C.S., L.J.), College Station, Texas 77843

Address all correspondence and requests for reprints to: Tim Zacharewski, Ph.D., Department of Biochemistry and Molecular Biology, 223 Biochemistry Building, Wilson Road, Michigan State University, East Lansing, Michigan 48824. E-mail: . tzachare{at}msu.edu

The objective of the study was to determine the long-term effects of gestational and lactational exposure to diethylstilbestrol (DES; 0, 0.1, 1, and 10 µg/kg maternal body weight) on mouse testicular growth, epididymal sperm count, in vitro fertilizing ability, and testicular gene expression using cDNA microarrays and real-time PCR in mice on postnatal day (PND) 21, 105, and 315. In the high dose group there was a persistent decrease in the number of Sertoli cells, and sperm count was decreased on PND315 (P < 0.05). Sperm motion was unaffected; however, the in vitro fertilizing ability of epididymal sperm was decreased in the high dose group on both PND105 (P < 0.001) and PND315 (P < 0.05). Early and latent alterations in the expression of genes involved in estrogen signaling (estrogen receptor ), steroidogenesis (steroidogenic factor 1, 17-hydroxylase/C17,20-lyase, P450 side chain cleavage, steroidogenic acute regulatory protein, and scavenger receptor class B1), lysosomal function (LGP85 and prosaposin), and regulation of testicular development (testicular receptor 2, inhibin/activin ß C, and Hoxa10) were confirmed by real-time PCR. The results demonstrate that early exposure to DES causes long-term adverse effects on testicular development and sperm function, and these effects are associated with changes in testicular gene expression, even long after the cessation of DES exposure.

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