Effects of Bisphenols on Testicular Steroidogenesis

Abstract

Over the last decades, the adverse effects of human exposure to the so-called “endocrine disruptors” have been a matter of scientific debate and public attention. Bisphenols are synthetic chemicals, widely used in the manufacture of hard plastic products. Bisphenol A (BPA) is one of the best-known environmental toxicants proven to alter the reproductive function in men and to cause other health problems. Consumer concern resulted in “BPA free” products and in the development of bisphenol analogs (BPA-A) to replace BPA in many applications. However, these other bisphenol derivatives seem to have effects similar to those of BPA. Although a number of reviews have summarized the effects of BPA on human reproduction, the purpose of this article is to review the effects of bisphenols on testicular steroidogenesis and to explore their mechanisms of action. Testicular steroidogenesis is a fine-regulated process, and its main product, testosterone (T), has a crucial role in fetal development and maturation and in adulthood for the maintenance of secondary sexual function and spermatogenesis. Contradictory outcomes of both human and animal studies on the effects of BPA on steroid hormone levels may be related to various factors that include study design, dosage of BPA used in in vitro studies, timing and route of exposure, and other confounding factors. We described the main possible molecular target of bisphenols on this complex pathway. We report that Leydig cells (LCs), the steroidogenic testicular component, are highly sensitive to BPA and several mechanisms concur to the functional impairment of these cells.

Temporal Trend of Conventional Sperm Parameters in a Sicilian Population in the Decade 2011–2020

“…As an example, fetal exposure to bisphenol-A, a chemical with estrogenic activity, disrupted spermatogenesis damaging viability, motility, and sperm chromatin condensation of adult mice [ 36 ]. The negative impact of this chemical on human fertility has been already ascertained [ 37 ], as well as that of phthalates [ 38 ]. Similarly, fetal exposure to cigarette smoke in mice led to a dose-dependent decrease of epididymal sperm counts both in F1 and F2 male offspring, indicating a transgenerational deleterious effect [ 39 ].…”

Obesity and Male Reproduction: Do Sirtuins Play a Role?

“…A progressive decline in sperm quality has been described [7,8]. Lifestyle and environmental factors, such as smoking [9], obesity [10], endocrine disruptors [11,12], an exposure to heavy metals [13,14], or psychological stress [15] may have a major role in the decreased sperm quality.…”

Interferenti endocrini e funzione gonadica: focus su steroidogenesi testicolare e infertilità maschile

“…Nonostante l'incoerenza degli studi clinici, studi in modelli animali e in vitro hanno individuato potenziali meccanismi d'azione alla base della potenziale disfunzione gonadica maschile; il trattamento con BPA impatta su spermatogenesi e steroidogenesi testicolare maggiormente per interferenza endocrina con l'asse ipotalamo-ipofisi-testicolo e per inibizione diretta dell'attività della proteina StAR e degli enzimi steroidogenici 3-β-idrossisteroide deidrogenasi e 17β-idrossisteroide deidrogenasi, induzione dell'iperespressione dell'aromatasi, riduzione del numero di cellule germinali, del Sertoli, e di Leydig indotta da iperespressione dei mediatori apoptotici Fas e Fas ligando a livello testicolare, alterazione del signaling di glucosio e insulina e dell'attività mitocondriale in cellule germinali e di Leydig, e disfunzione del sistema antiossidante a livello testicolare con conseguente stress ossidativo (Fig. 1) [6,10].…”