Effects of Elevated β-Estradiol Levels on the Functional Morphology of the Testis - New Insights

Abstract

Elevated estradiol levels are correlated with male infertility. Causes of hyperestrogenism include diseases of the adrenal cortex, testis or medications affecting the hypothalamus-pituitary-gonadal axis. The aim of our study was to elucidate the effects of estradiol treatment on testicular cellular morphology and function, with reference to the treatment regimen received. Testes samples (n = 9) were obtained post-orchiectomy from male-to-female transsexuals within the age range of 26–52 years. Each patient had a minimum of 1–6 years estradiol treatment. For comparison, additional samples were obtained from microscopically unaltered testicular tissue surrounding tumors (n = 7). The tissues obtained were investigated by stereomicroscopy, histochemistry, scanning electron microscopy (SEM) and immunohistochemistry. Our studies revealed that estradiol treatment significantly decreased the diameter of the seminiferous tubules (p < 0.05) and induced fatty degeneration in the surrounding connective tissue. An increase in collagen fiber synthesis in the extracellular matrix (ECM) surrounding the seminiferous tubules was also induced. Spermatogenesis was impaired resulting in mainly spermatogonia being present. Sertoli cells revealed diminished expression of estrogen receptor alpha (ERα). Both Sertoli and Leydig cells showed morphological alterations and glycoprotein accumulations. These results demonstrate that increased estradiol levels drastically impact the human testis.

Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood

“…PBB-associated CpGs also massively overlap with estradiol-associated CpGs, and the effect sizes of CpGs associated with estradiol is correlated with the effect sizes seen with PBB. PBB exposure being associated with estrogen-related transcription factor binding sites and with the epigenetic signal from estrogen may help explain the epidemiological findings in this cohort, which found an increase in genitourinary conditions in males exposed in utero through PBBs crossing the placental barrier [29], and an early age of menarche and an increased risk of spontaneous abortion in women exposed in utero [30,31], all of which are influenced by estrogen levels [66][67][68]. This could potentially indicate that PBB is acting as a weak estrogen on the epigenome and increasing exposure affects people's risk for endocrine related disorders.…”

Influence of prenatal waterpipe tobacco smoke exposure on reproductive hormones and oxidative stress of adult male offspring rats

“…However, oestrogen has been shown to play a critical role in the development of male reproductive organs (Cooke, Nanjappa, Ko, Prins, & Hess, ) and in spermatogenesis (Carreau, Bouraima‐Lelong, & Delalande, ). Elevated levels of estradiol, the biologically active form of oestrogen, have been shown to impair spermatogenesis and negatively alter the function and morphology of testicular Sertoli and Leydig cells in rats (Leavy et al, ). The current study show elevated levels of testicular oestrogen in adult male offspring rats with in utero exposure to WTS.…”

Bisphenol A Exposure during Pregnancy Alters the Mortality and Levels of Reproductive Hormones and Genes in Offspring Mice

“…The increased concentration of this estrogen indicates the estrogenic effect of BPA. This finding points to a hormonal imbalance that can cause disorders in histopathological changes in the testis and ovary [32]. Regulation of reproductive processes occurs directly through the influence of T and indirectly through its metabolites, DHT and E 2 .…”