The possible effects of p-nonylphenol, an environmental toxicant with estrogenic properties, on fertility

Abstract

Cryptorchidism, hypospadia, testicular cancer and a striking decline in sperm count are reported to occur more frequently now than 30-50 years ago. It has been hypothesized that these male reproductive abnormalities may be amongst others due to an increased level of maternal estrogens affecting the developing fetus. Estrogenic substances include a number of medications, waste products, pesticides and insecticides, and substances used as additives or surfactants in the manufacturing of plastics, like p-nonylphenol (p-NP}. Estrogenic contamination of p-NP may occur through food, water and in the workplace. In this study p-NP, an environmental toxicant with estrogenic properties, was investigated for its possible effects on fertility. The pilot studies consisted of a LD50-test, reproductive test and a dose range finding test to find the appropriate p-NP concentration for evaluation in the main study. The effect of maternal (fetal and neonatal} and adult p-NP exposure on the male reproductive tract, with special reference to spermatogenesis was established. The OECD (415} one generation test was selected as guideline in the design of the main study. It was modified to accommodate two experimental groups, one on adult exposure (AT) to p-NP, and the second on maternal exposure {MT) on fetal and postnatal development, continuing for duration of their lifespan (10 weeks). Sprague-Dawley rats were used and animals from both experiments were exposed to dosages of 100, 250, and 400 mg/kg p-NP respectively, as determined from the pilot studies. The results showed that when adult males were exposed to 100 mg/kg p-NP the histological parameters of the seminiferous tubules were adversely affected. Increasing the level to 250 mg/kg resulted additionally in a smaller weight gain and signs of epididymal toxicity, while 400 mg/kg p-NP also impaired testicular mass and sperm count. In the last two groups the process of spermatogenesis was also affected in some animals. In the MT experiment a dose level of 100 mg/kg adversely affected body and testicular mass, as well as histological measurements of the germinal epithelium. However, at a higher level of exposure (250 mg/kg) the epididymal mass and total sperm count were additionally negatively influenced. Therefore, p-NP was toxic on both the testis and epididymis and both venues might be important in impairing male fertility. The histological findings, including germ cell necrosis, apical sloughing, and vacuolization, might be the first evidence of an effect of p-NP on the testis. These findings indicated that p-NP is a Sertoli cell toxicant. Fetal exposure enhanced the adverse effects in the MT group, compared to the AT group, supporting the hypothesis that reproductive abnormalities might be due to maternal exposure. Bio-accumulation may enhance the negative effects at even lower p-NP concentrations over longer exposure periods than reported here. The poor conception rate and small litter size unfortunately nullified its use to indicate the clinical effect of the testicular and epididymal toxicity and these should be confirmed in future studies.