Gestational and lactational exposure of rats to xenoestrogens results in reduced testicular size and sperm production.

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 or concentrations of 10-1000 micrograms/l (OP) or 1000 micrograms/l (BBP), diethylstilbestrol (DES; 100 micrograms/l) and an octylphenol polyethoxylate (OPP; 1000 micrograms/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 tap water. In study 1, rats were treated from days 1-22 after births in studies 2 and 3, the mothers were treated for approximately 8-9 weeks, spanning a 2-week period before mating throughout gestation and 22 days after giving birth. With the exception of DES, treatment generally had no major adverse effect or 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 micrograms/1 resulted in a small (5-13%) but significant (p < 0.01 or p < 0.0001) 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 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. ImagesFigure 1.Figure 2.Figure 3. AFigure 3. BFigure 3. CFigure 3. DFigure 4.

[1]  M. Waldock,et al.  Concentrations of alkylphenols in rivers and estuaries in England and Wales , 1995 .

[2]  J. Sumpter,et al.  A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic. , 1995, Environmental health perspectives.

[3]  R. Sharpe Could environmental, oestrogenic chemicals be responsible for some disorders of human male reproductive development? , 1994 .

[4]  J. Sumpter,et al.  Environmentally persistent alkylphenolic compounds are estrogenic. , 1994, Endocrinology.

[5]  R. Sharpe,et al.  Temporal relationship between androgen-dependent changes in the volume of seminiferous tubule fluid, lumen size and seminiferous tubule protein secretion in rats. , 1994, Journal of reproduction and fertility.

[6]  J Gilbert,et al.  Levels of di-(2-ethylhexyl)phthalate and total phthalate esters in milk, cream, butter and cheese. , 1994, Food additives and contaminants.

[7]  W. Giger,et al.  Behaviour of alkylphenol polyethoxylate surfactants in the aquatic environment-II. Occurrence and transformation in rivers , 1994 .

[8]  C. Sonnenschein,et al.  The pesticides endosulfan, toxaphene, and dieldrin have estrogenic effects on human estrogen-sensitive cells. , 1994, Environmental health perspectives.

[9]  John P. Sumpter,et al.  Detergent components in sewage effluent are weakly oestrogenic to fish: An in vitro study using rainbow trout (Oncorhynchus mykiss) hepatocytes , 1993 .

[10]  D. Feldman,et al.  Bisphenol-A: an estrogenic substance is released from polycarbonate flasks during autoclaving. , 1993, Endocrinology.

[11]  R. M. Sharpe,et al.  Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? , 1993, The Lancet.

[12]  R M Sharpe,et al.  Declining sperm counts in men--is there an endocrine cause? , 1993, The Journal of endocrinology.

[13]  N. Keiding,et al.  Evidence for decreasing quality of semen during past 50 years. , 1992, BMJ.

[14]  W. Adams,et al.  Alkylphenol ethoxylates in the environment , 1992 .

[15]  Irwin H. Suffet,et al.  Determination of Alkylphenol Ethoxylates and Their Acetic Acid Derivatives in Drinking Water by Particle Beam Liquid Chromatography/Mass Spectrometry , 1992 .

[16]  B. Page,et al.  Studies into the transfer and migration of phthalate esters from aluminium foil-paper laminates to butter and margarine. , 1992, Food additives and contaminants.

[17]  R. Sharpe,et al.  Testosterone and spermatogenesis. Identification of stage-specific, androgen-regulated proteins secreted by adult rat seminiferous tubules. , 1992, Journal of andrology.

[18]  C. Sonnenschein,et al.  p-Nonyl-phenol: an estrogenic xenobiotic released from "modified" polystyrene. , 1991, Environmental health perspectives.

[19]  W. Berndtson,et al.  Changing relationships between testis size, Sertoli cell number and spermatogenesis in Sprague-Dawley rats. , 1990, Journal of andrology.

[20]  L. A. Dostal,et al.  Testicular toxicity and reduced Sertoli cell numbers in neonatal rats by di(2-ethylhexyl)phthalate and the recovery of fertility as adults. , 1988, Toxicology and applied pharmacology.

[21]  J. Orth,et al.  Evidence from Sertoli cell-depleted rats indicates that spermatid number in adults depends on numbers of Sertoli cells produced during perinatal development. , 1988, Endocrinology.

[22]  L. A. Dostal,et al.  Transfer of di(2-ethylhexyl) phthalate through rat milk and effects on milk composition and the mammary gland. , 1987, Toxicology and applied pharmacology.

[23]  R. Sharpe,et al.  Follicle-Stimulating Hormone Induction of Ley dig Cell Maturation , 1985 .

[24]  A. Christensen,et al.  Morphometric studies on rat seminiferous tubules. , 1982, The American journal of anatomy.

[25]  L. Johnson,et al.  A new approach to quantification of spermatogenesis and its application to germinal cell attrition during human spermiogenesis. , 1981, Biology of reproduction.

[26]  L. Johnson,et al.  A comparative study of daily sperm production and testicular composition in humans and rats. , 1980, Biology of reproduction.

[27]  A. R. Singh,et al.  Maternal-fetal transfer of 14C-di-2-ethylhexyl phthalate and 14C-diethyl phthalate in rats. , 1975, Journal of pharmaceutical sciences.

[28]  J. Autian Toxicity and health threats of phthalate esters: review of the literature. , 1973, Environmental health perspectives.

[29]  James L. Johnson,et al.  Phthalate Esters as Environmental Contaminants , 1972, Nature.

[30]  C. P. Leblond,et al.  DEFINITION OF THE STAGES OF THE CYCLE OF THE SEMINIFEROUS EPITHELIUM IN THE RAT , 1952, Annals of the New York Academy of Sciences.

[31]  P. Cooke,et al.  Induction of increased testis growth and sperm production in adult rats by neonatal administration of the goitrogen propylthiouracil (PTU): the critical period. , 1992, Biology of reproduction.

[32]  T. Colborn,et al.  Chemically-induced alterations in sexual and functional development : the wildlife/human connection , 1992 .

[33]  R. Sharpe,et al.  Follicle-stimulating hormone induction of Leydig cell maturation. , 1985, Endocrinology.

[34]  A. R. C. Teohnical LONDON: HER MAJESTY'S STATIONERY OFFICE , 1942 .