Mechanisms of Testicular Disruption from Exposure to Bisphenol A and Phtalates

Abstract

Great attention has been paid in recent years to the harmful effects of various chemicals that interfere with our natural hormone balance, collectively known as endocrine-disrupting chemicals (EDCs) or endocrine disruptors. The effects on the reproductive system of bisphenol A (BPA) and phthalates have received particular attention: while they have a short half-life, they are so widespread that human exposure can be considered as continuous. Evidence is often limited to the animal model, disregarding the likelihood of human exposure to a mixture of contaminants. Data from animal models show that maternal exposure probably has harmful effects on the male fetus, with an increased risk of urogenital developmental abnormalities. After birth, exposure is associated with changes in the hypothalamic-pituitary-testicular axis, hindering the development and function of the male genital pathways through the mediation of inflammatory mechanisms and oxidative stress. The epidemiological and clinical evidence, while generally confirming the association between reproductive abnormalities and some phthalate esters and BPA, is more contradictory, with wildly different findings. The aim of this review is therefore to provide an update of the potential mechanisms of the damage caused by BPA and phthalates to reproductive function and a review of the clinical evidence currently available in the literature.

Phthalates and Bisphenol A: Presence in Blood Serum and Follicular Fluid of Italian Women Undergoing Assisted Reproduction Techniques

“…In general, animal models have shown that EDCs can affect Hypothalamic-Pituitary-Gonadal (HPG) axis and ovarian function, pubertal development, and trophoblast/placental function [ 16 ]. Organochlorine compounds, pesticides and estrogenic drugs have been extensively studied, but a growing amount of data are investigating the impact of compounds such as phthalate esters and phenols (and bisphenol A in particular) [ 9 ]. These are frequently found in commonly used plastic products and, despite their short half-life, human contact is so common that exposure can be considered continuous [ 17 ].…”

“…Several animal studies have showed that exposure to DEHP (among the most common phthalates diesters) altered sexual differentiation, inhibited androgen production, reduced testicular testosterone levels, and shortened anogenital distance (AGD) in male rats [ 9 ]. In female rats, DHEP and the monoester metabolite MEHP provoked a reduction of serum estradiol and progesterone likely mediated by inhibition of the transcription of aromatase enzyme (P450arom) that converts androgens to estrogens [ 1 ].…”

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 ].…”

Use of polyethyleneoxide and hydroxyethylstarch as blood plasma substitutes in the cryopreservation of testis interstitium cells in mice

“…Різноманітні аномалії чоловічої статевої системи (наприклад, крипторхізм) та шкідливі фактори навколишнього середовища обумовлюють дисфункцію клітин Лейдіга, що в свою чергу призводить до захворювань, пов'язаних із недостатністю андрогенів [1]. Наприклад, було продемонстровано, що аналоги естрогенів, такі як бісфенол А, можуть знижувати продукцію сперматозоїдів, порушуючи функцію клітин Лейдіга і пригнічуючи секрецію тестостерону [2]. Ожиріння також може знижувати кількість клітин Лейдіга і секрецію тестостерону та погіршувати репродуктивну функцію [3].…”