The cumulative effects of environmental toxicants, for example, the alkylphenol, para-nonylphenol (p-NP) are of concern. Our previous study showed that p-NP reduced several testicular morphometric parameters, including sperm counts. The present study reexamined material collected in that study to determine the mechanistic basis of p-NP action on spermatogenic development in the offspring. Seven-day pregnant Sprague-Dawley rats were treated with vehicle or 100 or 250 mg/kg p-NP through gestation, lactation and afterward directly to all male offspring until 10 weeks of age. Both doses of p-NP significantly (P < 0.02) increased the number of germ cells with in situ end-labeled fragmented DNA (TUNEL positive) by 1.9-fold and 1.7-fold, respectively, and specifically in stages XII-XIV and I-III. TUNEL-labeling was, however, selective, and excluded labeling of basal cells with apoptotic morphology. Cleaved caspase-3 immunohistochemistry strongly labeled basal cells (spermatogonia and early spermatocytes) with condensed marginated chromatin but not degenerate germ cells lacking definitive nuclear material found throughout the epithelium. Only the caspase index (ratio of number of caspase positive to number of degenerate cells) of the 100-mg/kg p-NP group was significantly (p < 0.05) threefold greater than controls. Whereas both doses and either 250 or 100 mg/kg treatment alone significantly (p < 0.002) reduced the frequencies (duration) of stages I-III, VII-VIII, and late VIII-IX (spermiating and recently spermiated tubules), respectively, both doses significantly (p < 0.002) increased the frequencies of stages IV-VI and all stages containing late-stage spermatocytes (XII-XIII) and meiotic cell divisions (XIV). Thus, p-NP, an environmentally persistent xenoestrogen, insidiously alters the spermatogenic cycle and spermatogenic process in male offspring.

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ContentsThis study deals with disorders of sexual development in humans, wildlife and animals in an urban nature reserve (RNR) and a currently DDT-sprayed malarial area. High levels of oestrogenic chemical residues in water, sediment and tissue; skewed sex ratios; reduced biodiversity; gonadal malformations in sharptooth catfish and freshwater snails; intersex in catfish; and impaired spermatogenesis in catfish and striped mouse are of serious concern in the RNR. Persistent eggshell thinning in African darter eggs, intersex in male Mozambican tilapia, follicular atresia in females and impaired spermatogenesis in males following laboratory exposure of parent fish to environmentally relevant DDT and DDE concentrations, and abnormalities in freshwater snails were found in the DDT-sprayed area. Human studies related to DDT exposure indicated impaired semen quality, a weak association with sperm chromatin defects and higher risks for external urogenital birth defects in those who were born to mothers whose houses were sprayed and those who were homemakers (stay at home mother) instead of being employed. These findings indicate that diseases of sexual development occurred in both human and wildlife populations exposed to environmental endocrine disruptor chemicals in South Africa. The chemical mixtures, possibly related to disorders of sexual differentiation (DSD), were very different between the two. However, DSD occurred concurrently in the malarial area, possibly indicating that humans and wildlife shared exposures. Moreover, it emphasizes the importance of suspecting disease in the other when disease is found in either human or wildlife populations.

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