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GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE PERMANENTLY ALTERS REPRODUCTIVE COMPETENCE IN THE CD-1 MOUSE
Citation:
Tarka, D. K., J D. Suarez, N L. Roberts, J M. Rogers, M. P. Hardy, AND G R. Klinefelter. GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE PERMANENTLY ALTERS REPRODUCTIVE COMPETENCE IN THE CD-1 MOUSE. BIOLOGY OF REPRODUCTION 69(3):959-967, (2003).
Description:
While the adult mouse Leydig cell (LC) has been considered refractory to cytotoxic destruction by ethane dimethanesulfonate (EDS), the potential consequences of exposure during reproductive development in this species are unknown. Herein pregnant CD-1 mice were treated with 160 mg/kg on gestation days (GD) 11-17, and reproductive development in male offspring was evaluated. Prenatal administration of EDS compromised fetal testosterone (T) levels compared to controls. EDS exposed pups recovered their steroidogenic capacities after birth as T production by hCG-stimulated testis parenchyma from prepubertal male offspring was unchanged. However, prepubertal testes from prenatally exposed males contained seminiferous tubules (ST) devoid of germ cells, indicating a delay in spermatogenesis. In adults, some STs in exposed males still contained incomplete germ cell associations corroborating observed reductions in epididymal sperm reserves, fertility ratios, and litter size. Morphometry revealed an EDS-induced increase in interstitial area and a concomitant decrease in ST area, but stereology revealed an unexpected decrease in the number and size of the LCs per testis in exposed males. Paradoxically, there was an increase in both serum luteinizing hormone (LH) and T production by adult testis parenchyma, indicating that the LCs were hyperstimulated. A proteomic evaluation of neonatal testes revealed that three proteins implicated in steroidogenesis were diminished: apolipoprotein A-1, phosphatidylethanolamine, and thioredoxin-like protein. These data demonstrate permanent lesions in LC development and spermatogenesis caused by prenatal exposure in mice. Thus, while adult mouse LCs are insensitive to EDS, EDS appears to have direct action on fetal LCs, resulting in abnormal testis development.