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Abstract

Gestational exposure to ethane dimethanesulfonate permanently alters reproductive competence in the CD-1 mouse (PDF) (HTML) 
Tarka-Leeds,Dana K.; Suarez,Juan D.; Roberts,Naomi L.; Rogers,John M.; Hardy,Matthew P.; Klinefelter,Gary R.
Biology of Reproduction 69(3): 959-967
Publication date: 2003

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Although the adult mouse Leydig cell (LC) has been consideredrefractory to cytotoxic destruction by ethane dimethanesulfonate(EDS), the potential consequences of exposure during reproductivedevelopment in this species are unknown. Herein pregnant CD-1mice were treated with 160 mg/kg on Gestation Days 11-17,and reproductive development in male offspring was evaluated.Prenatal administration of EDS compromised fetal testosterone(T) levels, compared with controls. EDS-exposed pups recoveredtheir steroidogenic capacities after birth because T productionby hCG-stimulated testis parenchyma from prepubertal male offspringwas unchanged. However, prepubertal testes from prenatally exposedmales contained seminiferous tubules (STs) devoid of germ cells,indicating a delay in spermatogenesis. In adults, some STs inexposed males still contained incomplete germ cell associationscorroborating observed reductions in epididymal sperm reserves,fertility ratios, and litter size. Morphometry revealed an EDS-inducedincrease in interstitial area and a concomitant decrease inST area, but stereology revealed an unexpected decrease in thenumber and size of the LCs per testis in exposed males. Paradoxically,there was an increase in both serum LH and T production by adulttestis parenchyma, indicating that the LCs were hyperstimulated.These data demonstrate permanent lesions in LC development andspermatogenesis caused by prenatal exposure in mice. Thus, althoughadult mouse LCs are insensitive to EDS, EDS appears to havedirect action on fetal LCs, resulting in abnormal testis development.

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