Relationship between expression of sex steroid receptors and structure of the seminal vesicles after neonatal treatment of rats with potent or weak estrogens.

Abstract

In this study we evaluated the effect of manipulating the estrogen and androgen environment of the neonatal male rat on subsequent immunoexpression of sex steroid receptors in the seminal vesicles (SVs) at age 18 days. The aim was to establish to what extent such changes were associated with and predictive of changes in SV structure/composition. Treatments were either diethylstilbestrol (DES; 10, 1, or 0.1 microg/injection), ethinyl estradiol (EE; 10 microg/injection), tamoxifen (2 mg/kg/day), flutamide (50 mg/kg), a gonadotropin-releasing hormone antagonist (GnRHa; 10 mg/kg), genistein (4 mg/kg/day), octylphenol (2 mg/injection), or bisphenol A (0.5 mg/injection). Compared with controls, treatment with DES (10 microg) induced loss of epithelial and stromal androgen receptor (AR) immunoexpression coincident with induction of stromal progesterone receptor (PR) immunoexpression and upregulation of stromal immunoexpression of estrogen receptor-alpha (ERalpha). These changes were associated with gross distortion (increase) of the normal stromal:epithelial tissue proportions in the SVs. DES (1 microg) and EE induced similar but less pronounced changes, and DES (0.1 microg) had no noticeable effect. Tamoxifen and flutamide induced PR and slightly upregulated ERalpha immunoexpression but had only a minor or no effect on AR expression and the stromal:epithelial ratio, though flutamide retarded normal development of the SVs. The latter was also evident in GnRHa-treated males, but otherwise this treatment had no effect on AR and PR immunoexpression. None of the foregoing treatments had any detectable effect on the immunoexpression of ERss in stromal or epithelial cells. The major treatment-induced changes in immunoexpression of AR, PR, and ERalpha and lack of change in ERss were confirmed by Western blots of SV protein extracts. None of the three weak (environmental) estrogens tested caused any detectable change in sex steroid receptor immunoexpression or SV tissue composition. We conclude that treatment-induced loss of AR is a prerequisite for altered stromal:epithelial proportions in the SVs and that such loss is always associated with induction of PR and upregulation of ERalpha; the latter two changes are insufficient on their own to bring about such a change. Nevertheless, induction of PR expression was always associated with altered SV development and is a potentially useful marker because it is not normally expressed in male reproductive tissues.

Altered profiles of spontaneous novelty seeking, impulsive behavior, and response to D-amphetamine in rats perinatally exposed to bisphenol A.

“…Long-term exposure of adult female rats to BPA induces modifications in β-estrogen receptor immunoreactivity in various brain areas regulating reproductive and maternal behavior (Aloisi et al 2001). Many studies have addressed the adverse effects of perinatal exposure to BPA on various indexes of sexual development and maturation (Atanassova et al 2000;Fisher et al 1999;Rubin et al 2001;Williams et al 2001aWilliams et al , 2001b. Unfortunately, little is known about the effect of estrogen-like compounds on developing monoamine systems.…”

“…It is not only widespread but also potentially ingested by humans, being released by polycarbonate plastics, the lining of food cans, and dental sealants (Brotons et al 1995;Olea et al 1996). Prenatal exposure to BPA can affect the development and function of reproductive organs as well as adult sexual behavior, especially in male rodents and in their offspring (Atanassova et al 2000;Dessì-Fulgheri et al 2002;Farabollini et al 2002;Fisher et al 1999;Howdeshell et al 1999;Rubin et al 2001;Vom Saal et al 1995Williams et al 2001aWilliams et al , 2001b. Perinatal exposure to BPA has also been implicated in altered profiles of nonsocial behaviors, resulting in a reduced motivation to explore and a reduced anxiety in the male offspring (Farabollini et al 1999).…”

Endocrine disrupting chemicals: a new and emerging public health problem?

“…14 This has since been expanded to include environmental chemicals with anti-androgen actions and it is now thought that an imbalance between androgen and oestrogen activity is the key mechanism by which exposure to EDCs results in the development of TDS and male reproductive tract abnormalities. 15 Some chemicals with known EDC activity interact at a molecular level with oestrogen and androgen receptors thereby potentially interfering with sex hormone dependent regulation of specific developmental programming genes. Examples include the Hox genes, which play a pivotal role in the normal differentiation of the reproductive tract and are directly modulated by potent synthetic non-steroidal oestrogen agents such as diethylstilbestrol (DES).…”

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

“…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.…”

“…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].…”