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Richard M. Sharpe,¹ Jane S. Fisher,¹ Mike M. Millar,¹ Susan Jobling,² and John P. Sumpter²

¹MRC Reproductive Biology Unit, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9EW, Scotland
²Department of Biology and Biochemistry, Brunel University, Uxbridge, Middlesex UB8 3PH UK

Abstract

This study assessed whether exposure of male rats to two estrogenic, environmental chemicals, 4-octylphenol (OP) and butyl benzyl phthalate (BBP) during gestation or during the first 21 days of postnatal life, affected testicular size or spermatogenesis in adulthood (90-95 days of age) . Chemicals were administered via the drinking water at concentrations of 10-1000 µg/l (OP) or 1000 µg/l (BBP) ; diethylstilbestrol (DES ; 100 µg/l) and an octylphenol polyethoxylate (OPP ; 1000 µg/l) , which is a weak estrogen or nonestrogenic in vitro , were administered as presumptive positive and negative controls, respectively. Controls received the vehicle (ethanol) in tapwater. In study 1, rats were treated from days 1-22 after birth ; in studies 2 and 3, the mothers were treated for approximately 8-9 weeks, spanning a 2-week period prior to mating, throughout gestation and up until 22 days postnatal after giving birth.

With the exception of DES, treatment generally had no major adverse effect on body weight. In most instances, treated animals were heavier than controls at day 22 and at days 90-95. Exposure to OP, OPP or BBP at a concentration of 1000 µg/l resulted in a small (5-13%) but significant (p<0.01 or p<0.001) reduction in mean testicular size in studies 2 and 3, an effect that was still evident when testicular weight was expressed relative to body weight or kidney weight. The effect of OPP is attributed to its metabolism in vivo to OP. DES exposure caused similar reductions in testicular size but also caused reductions in body weight, kidney weight, and litter size. Ventral prostate weight was reduced significantly in DES-treated rats and to a minor extent in OP-treated rats. Comparable but more minor effects of treatment with DES or OP on testicular size were observed in study 1. None of the treatments had any adverse effect on testicular morphology or on the cross-sectional area of the lumen or seminiferous epithelium at stages VII-VIII of the spermatogenic cycle, but DES, OP and BBP caused reductions of 10-21% (p<0.05 to p<0.001) in daily sperm production. Humans are exposed to phthalates, such as BBP, and to alkylphenol polyethoxylates, such as OP, but to what extent is unknown. More detailed studies are warranted to assess the possible risk to the development of the human testis from exposure to these and other environmental estrogens. Key words: butyl benzyl phthalate, daily sperm production, diethylstilbestrol, 4-octylphenol, Sertoli cell number, spermatogenesis. Environ Health Health Perspect 103:1136-1143 (1995)

Address correspondence to R.M. Sharpe, MRC Reproductive Biology Unit, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9EW, Scotland.

We are grateful to Jim McDonald for expert help with the animals in these studies.

Received 7 June 1995 ; accepted 10 August 1995.