Effects of Maternal Exposure to Diethylstilbestrol on Epididymal Development in Rat Offspring

Abstract

ABSTRACT. In our previous study, prenatal diethylstilbestrol (DES) exposure (days 7-21 of gestation) suppressed plasma testosterone levels and histological development in the epididymis of rat offspring. In this study, we measured cell proliferation in epididymal ductules and the expression of steroid hormone receptors and 5-reductase 1 in the epididymis to assess the effect of DES on epididymal development in the offspring. Prenatal DES exposure did not alter the cell division index, but suppressed the expression of androgen receptor mRNA at 15 weeks after birth, and stimulated estrogen receptor  mRNA at 6 weeks. These results suggest that prenatal DES exposure results in the retardation of epididymal tissue maturation by disruption of the postnatal expression of steroid hormone receptors.KEY WORDS: DES, epididymis, rat.J. Vet. Med. Sci. 71(3): 375-378, 2009 Androgen plays an important role in the development and function of the testis and male reproductive tract via the androgen receptor (AR) in mammals. Similarly, since estrogen receptors (ERs) in those tissues have been demonstrated [5,9,15,16,19], estrogen may be involved in the development of the male reproductive system. The mechanism via which brief estrogen exposure during development can lead to permanent structural and functional changes to the male reproductive tract are still unclear. Studies in rats treated neonatally with DES, have shown the impaired development of the epithelium and relative overgrowth of stromal tissue in the epididymis [2,21], vas deferens [2], seminal vesicles [22], and prostate [16,22], during or soon after the cessation of treatment. These gross structural changes are associated with a reduced expression of the AR [10,12,13,21,22], and with the induction of the abnormal expression of estrogen receptor  [ER; 2,14,22].Our previous study demonstrated that fetal administration of a low dose of DES induced a low level of testosterone, which led to a slight modification of spermatogenesis at 15 weeks, instead of a more extensive disruption of the morphological development of the epididymis, reducing the weight of the epididymis, the height of epididymal tubule epithelial cells, and luminal diameters [23]. Therefore, we speculated on which fetal DES treatment effects the cell proliferation of epididymal tubule epithelial cells.A previous study reported that the administration of DES to rat pups inhibited cell proliferation in the epididymis [2]. In this study, we attempted to confirm whether the gross anatomical changes in the epididymis induced by fetal treatment with DES are the result of the inhibition of epididymal cell proliferation. In addition, we examined the changes in steroid hormone receptor expression to elucidate the mechanism of the effect of fetal DES administration on the epididymis of offspring.Sprague-Dawley rats (Japan SLC, Hamamatsu, Japan) were given a commercial diet (CE-2, CLEA , Tokyo, Japan) and water, both ad libitum. Females were mated with males overnight and were examined the next morning for the...

Estrogen receptors and function in the male reproductive system

“…It has been shown that reduction of the endogenous estrogen by treatment with an aromatase inhibitor delayed epididymal development in boars (57). The gestational exposure of rats to diethylstilbestrol decreased expression of the AR mRNA and stimulated the ESR1 mRNA in the offspring (59). Exposure of adult male rats to dietary phytoestrogens reduced fecundity, and increased ESR1 and AR mRNA in the initial segment, but decreased them in the cauda of the epididymis (60).…”

n‐butylparaben induces male reproductive disorders via regulation of estradiol and estrogen receptors

“…These data suggest that ERα, but not ERβ, plays a predominant role in mediating male reproductive toxicity after n-BP exposure. Related studies (Atanassova et al, 2005;Goyal et al, 2009;Prabhu et al, 2010;Yamamoto et al, 2009) reported that ERα mediation is a likely mechanism for the embryo and fetus maldevelopment induced by exposure to exogenous estrogenic chemicals in utero and via lactation. Our results support the aforementioned studies with the exception of differing target organs.…”

“…The absence of androgen down‐regulates AR expression in testicular and epididymal cells, which causes male infertility because spermatogenesis rarely progresses beyond meiosis (Walker, ). AR also regulates androgen action (Yamamoto et al , ). AR immunoreactivity was found in the nuclei of target cells of the prostate, testes and a variety of other organs.…”