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This Article Full Text Full Text (PDF) All Versions of this Article: 72/2/436    most recent biolreprod.104.033548v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Henderson, N. A. Articles by Robaire, B. Search for Related Content PubMed PubMed Citation Articles by Henderson, N. A. Articles by Robaire, B. Agricola Articles by Henderson, N. A. Articles by Robaire, B.

Effects of PNU157706, a Dual 5-Reductase Inhibitor, on Rat Epididymal Sperm Maturation and Fertility¹

Departments of Pharmacology and Therapeutics³ and of Obstetrics and Gynecology,⁴ McGill University, Montréal, Quebec, Canada H3G 1Y6

Sperm entering the epididymis gain progressive motility and fertilizing ability in a process termed maturation. The functional dependence of the epididymis on dihydrotestosterone (DHT) is well established, yet few studies have examined the consequences on the epididymis of inhibiting DHT formation. We have shown that inhibition of both isoforms of 5-reductase (types 1 and 2), the enzyme that converts testosterone to DHT, has pronounced effects on epididymal gene expression. In the present study, we investigate whether inhibiting 5-reductase has consequences on epididymal sperm maturation. Rats were treated with vehicle or 10 mg/kg/day PNU157706, a dual-type inhibitor, for 28 days. Fertility and several key facets of sperm maturation were analyzed. Changes in sperm motility were assessed by computer-assisted sperm analysis (CASA). Changes in sperm morphology were assessed by CASA and electron microscopy. The motility of spermatozoa from the cauda epididymidis of treated animals showed a significant decrease in both the percentage of motile and progressively motile sperm as well as altered motion parameters. The morphology of cauda epididymal spermatozoa was also adversely affected by the treatment; the most prominent effect was a markedly elevated proportion of sperm that retained their cytoplasmic droplet. Matings with treated males resulted in fewer successful pregnancies and a higher rate of preimplantation loss. Progeny outcome was unaffected. The compromised sperm motility and morphology likely contribute to the subfertility of inhibitor-treated rats. Our results indicate a role for dual 5-reductase inhibitors in further studies of epididymal physiology and as a potential component of a male contraceptive.

¹ Supported by a grant from the Canadian Institutes of Health Research.

² Correspondence: B. Robaire, Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Montréal, QB, Canada H3G1Y6. FAX: 514 398 7120; bernard.robaire{at}mcgill.ca

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