Gestational Exposure to Ethane Dimethanesulfonate Permanently Alters Reproductive Competence in the CD-1 Mouse

• Published in: Biology of reproduction 2003-09, Vol.69 (3), p.959-967
• Main Authors: TARKA-LEEDS, Dana K, SUAREZ, Juan D, ROBERTS, Naomi L, ROGERS, John M, HARDY, Matthew P, KLINEFELTER, Gary R
• Format: Article
• Language: English
• Subjects: Animals; Antispermatogenic Agents - toxicity; Biological and medical sciences; Drug toxicity and drugs side effects treatment; Female; Fertility - drug effects; Leydig Cells - drug effects; Male; Medical sciences; Mesylates - toxicity; Mice; Organ Size - drug effects; Pharmacology. Drug treatments; Pregnancy; Prenatal Exposure Delayed Effects; Random Allocation; Seminiferous Epithelium - cytology; Seminiferous Epithelium - drug effects; Spermatogenesis - drug effects; Spermatozoa - drug effects; Testis - drug effects; Testis - growth & development; Testosterone - blood; Toxicity: urogenital system
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.103.017343

Although 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 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 recovered their steroidogenic capacities after birth because T production by hCG-stimulated testis parenchyma from prepubertal male offspring was unchanged. However, prepubertal testes from prenatally exposed males contained seminiferous tubules (STs) 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 LH and T production by adult testis parenchyma, indicating that the LCs were hyperstimulated. These data demonstrate permanent lesions in LC development and spermatogenesis caused by prenatal exposure in mice. Thus, although adult mouse LCs are insensitive to EDS, EDS appears to have direct action on fetal LCs, resulting in abnormal testis development.