Reproductive Toxicity Study of Bisphenol A, Nonylphenol, and Genistein in Neonatally Exposed Rats

Abstract

Abstract:To investigate the endocrine-mediated effects of neonatal administration of the weak estrogenic compounds, bisphenol A, nonylphenol and genistein, were subcutaneously injected with these compounds at doses of 0.1, 1, and 10 µg/rat/day for 5 days starting on postnatal day 1. Rats were autopsied at 47-50 days. Positive control groups were given diethylstilbestrol (DES) at the same dose levels as the other chemicals. The ano-genital distance, age of vaginal opening and preputial separation, and estrus cyclicity for all living offspring were examined. No abnormalities by the injection of nonylphenol and genistein were detected in this study. In the BPA groups, ano-genital distance in the females in the 1 and 10 µg BPA groups was shorter than in the control group, and the ventral prostate weight was higher in the 10 µg BPA group than in the control group. On the other hand, in the DES groups, delayed preputial separation occurred later in the 0.1 and 1 µg groups than in the control group, and in the 10 µg groups, preputial separation was not completed.Also the estrous stage persisted in female of all DES groups. Underdevelopment of the seminal vesicle and prostate were observed in males of the 1 and 10 µg DES groups, and fewer ovarian corpus lutea, ovarian follicular cysts, and uterine glands, as well as increased uterine epithelial height and squamous metaplasia of the epithelium in the uterus were observed in females of all DES groups. We concluded that the findings observed in the weak estrogenic compound groups were not toxicologically relevant changes and that the present data provide valuable information for the neonatal exposure assay using weak estrogenic compounds. (J Toxicol Pathol 2005; 18: 203-207)

Licorice Extract Does Not Impair the Male Reproductive Function of Rats

“…Estrogens including phytoestrogens such as genistein were found to impair gonadal development and spermatogenesis [10,14,17,19,20,24,26]. It is well known that licorice possesses estrogenic activity [22,35,36,39,40].…”

“…Females and mice are more vulnerable than males and rats. It is known that licorice contains phytoestrogens such as glabridin, hispaglabridins, glabrene, isoliquiritigenin and isoprenyl as well as genistein [26,35,39,40]. It is of interest to note that low levels of phytoestrogens in rodent chow enhance epididymal sperm counts via a-estrogen receptors [29].…”

“…In addition, licorice was found to exert estrogen-like activity [22,35,36,39,40]. Like estrogen, phytoestrogens such as genistein have been found to impair spermatogenesis, and thereby induce deficit of sperm [10,14,17,19,20,24,26]. Such observations led us to investigate the effects of licorice on male reproductive function.…”

NTP‐CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A

“…Noda et al (2005), support not indicated, examined the effect of neonatal bisphenol A exposure on reproductive organs of Sprague-Dawley rats. For 5 days beginning on PND 1 (day of birth 5 PND 0), 6-10 pups/sex/group (drawn from 2 litters) were s.c. injected with olive oil vehicle or bisphenol A [purity not reported] at 0.0001, 0.001, or 0.010 mg/rat/day.…”

Oral exposure to low-dose of nonylphenol impairs memory performance in Sprague-Dawley rats

“…A study has shown that chronic application of NP can impair learning and memory and decrease exploratory activity in male mice (Mao et al, 2010). In contrast, some pre-viously performed studies did not show any effect on the reproductive tract after neonatal exposure to NP (Odum and Ashby, 2000;Noda et al, 2006). Additionally, perinatal exposure to NP did not affect locomotor activity or learning and memory performance in rat offspring (Flynn et al, 2002;Ferguson et al, 2000;Negishi et al, 2004).…”