Roles of membrane and nuclear estrogen receptors in spermatogenesis

Estrogens are present systemically in males and testicular estrogen concentrations are higher than peripheral concentrations due to testicular estrogen production. Despite extensive literature showing deleterious effects of perinatal estrogen administration on the testis and spermatogenesis, estrogen’s role in the normal testis and spermatogenesis, especially in humans, remains less clear. Various types of estrogen receptors, including estrogen receptor 1, estrogen receptor 2, and G protein-coupled estrogen receptor are expressed in testis and other male reproductive organs. Beginning in the 1970s, early treatment of mice with the potent synthetic estrogen diethylstilbestrol (DES) was used to produce adult reproductive abnormalities. These included impaired spermatogenesis and other testicular abnormalities, cryptorchid testes, epididymal cysts, inflammatory orchitis and epididymitis, and accessory organ abnormalities, frequently accompanied by infertility. There is also extensive literature documenting effects of early DES exposure on male reproductive tract development in animal models and humans.