Oestrogen action and male fertility: experimental and clinical findings

Abstract

A proper balance between androgen and oestrogen is fundamental for normal male reproductive development and function in both animals and humans. This balance is governed by the cytochrome P450 aromatase, which is expressed also under spatio-temporal control. Oestrogen receptors ERα and/or ERβ, together with the membrane-associated G-protein-coupled functional ER (GPER), mediate the effects of oestrogen in the testis. Oestrogen action in male reproduction is more complex than previously predicted. The androgen/oestrogen balance and its regulation in the masculinisation programming window (MPW) during foetal life is the most critical period for the development of the male reproductive system. If this balance is impaired during the MPW, the male reproductive system may be negatively affected. Recent data from genetically modified mice and human infertile patients have shown that oestrogens may promote the engulfment of live Leydig cells by macrophages leading to male infertility. We also discuss recent data on environmental oestrogen exposure in men and rodents, where a rodent-human distinction is crucial and analyse some aspects of male fertility potentially related to impaired oestrogen/androgen balance.

Sterile inflammation as a factor in human male infertility: Involvement of Toll like receptor 2, biglycan and peritubular cells

“…Blockers of aromatase, possibly interfering with Leydig cell aromatization of T11, reduce systemic and presumably also testicular levels of E2. Hence there is evidence, linking E2 to male infertility in mice and men8, which however must be further elucidated. Our cellular experimental data obtained in HTPCs support such a role.…”

“…Some of the changes typical for male infertility patients are also found in a transgenic mouse expressing human aromatase (AROM+678910). These mice have increased levels of testicular estradiol (E2) and after 4 months of age, show signs of deteriorating spermatogenesis and sterile inflammation, characterized by interstitial and peritubular fibrosis, increased presence of immune cells and elevated testicular levels of TNFalpha.…”

Cytotoxic effects of ZnO nanoparticles on mouse testicular cells

“…Research has shown that environmental estrogens, heavy metals, phytotoxins, mycotoxins, and NPs adversely affect the testes. [63][64][65][66] Heavy metals are also common environmental toxicants that adversely affect steroid biosynthesis, causing irreversible degeneration or atrophy of the seminiferous tubules, testicular injury, and sex hormone disturbances. 26,27,67 Since the development and use of engineered NPs, many studies have examined their adverse effects on the mouse testes.…”

Interacciones Epitelio-Mesenquimáticas en el Desarrollo Testicular

“…También se ha visto una mayor expresión de STAR asociada a la producción de progesterona en respuesta a la estimulación de células intersticiales de mLTC-1 con factores paracrinos a las célu-las sustentaculares como IGF1, FGF y TGFA (Hu et al, 2010). A su vez, son capaces de sintetizar estrógenos a partir de andrógenos a través del sistema aromatasa, influyendo negativamente en la esteroidogénesis intersticial (Li et al, 2015) (Fig. 2).…”