DES affects the expression of GPER in the gubernaculum testis

New insight into the role of environmental estrogens in the etiology of male reproductive system

2015 Study Abstract

Recent evidence suggested a positive correlation between environmental estrogens (EEs) and high incidence of abnormalities in male urogenital system. EEs are known to cause the abnormalities of testes development and testicular descent.

Diethylstilbestrol (DES) is a nonsteroidal synthetic estrogen that disrupts the morphology and proliferation of gubernacular cells, and its nongenomic effects on gubernaculum testis cells may be mediated by G protein-coupled estrogen receptor (GPER).

In this study, we detected the expression of GPER in mouse gubernacular testis and investigated the effects of DES on the expression of GPER in gubernaculum testis cells. RT-PCR analysis revealed that GPER mRNA was expressed in the gubernaculum. GPER protein was detected in the parenchymal cells of the gubernaculum early in development. Furthermore, we demonstrate that GPER inhibitor G15 relieved DES-induced inhibition of GPER expression in gubernaculum testis cell, but ER inhibitor ICI 182780 had the converse effects on DES-induced inhibition of GPER expression in these cells.

These data suggest that the effects of DES on mouse gubernaculum testis cells are mediated at least partially by the regulation of GPER expression.

Discussion

DES is a non-steroidal synthetic estrogen, which has been used as estrogen therapy to prevent miscarriages and other complications of pregnancy. Recent data demonstrated the occurrence of long-term effects after developmental exposure to DES, and the possibility for adverse effects to be transmitted to subsequent generations. Consequently, DES became the first and classic example of an in utero estrogenic toxicant in humans and animals.

To provide evidence that GPER mediates the rapid effects of EEs, we treated gubernaculums testis cells with DES. We found that DES inhibited the expression of GPER in gubernaculum testis cells. In addition, GPER inhibitor G15 relieved DES-induced inhibition of GPER expression in gubernaculum testis cell, but ER inhibitor ICI 182780 had the converse effects on DES-induced inhibition of GPER expression in these cells. Taken together, our data suggest that the rapid effects of DES on gubernaculums testis cells are unlikely to be mediated by ER but instead mediated by GPER.

In summary, in this study we demonstrated that GPER is expressed in gubernaculum testis at tissue, cellular, and molecular levels, and DES affects the expression of GPER in the cultured gubernaculums testis cells. The nongenetic effects of DES on gubernaculums testis are unlikely to be mediated by ER but instead mediated by GPER partly.

Therefore, our data provide new insight into the role of EEs in the etiology of male reproductive system and will help develop better approaches for the prevention and therapy of male reproductive malformation.

Sources and more information
  • Diethylstilbestrol affects the expression of GPER in the gubernaculum testis, International journal of clinical and experimental pathology, NCBI PubMed PMC4525951, 2015 June.
  • Expression of GPER in mouse gubernaculums testis featured image credit PMC4525951/figure/fig01.
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