Impact of endocrine disrupting chemicals and pharmaceuticals on Sertoli cell development and functions

Abstract

Sertoli cells play essential roles in male reproduction, from supporting fetal testis development to nurturing male germ cells from fetal life to adulthood. Dysregulating Sertoli cell functions can have lifelong adverse effects by jeopardizing early processes such as testis organogenesis, and long-lasting processes such as spermatogenesis. Exposure to endocrine disrupting chemicals (EDCs) is recognized as contributing to the rising incidence of male reproductive disorders and decreasing sperm counts and quality in humans. Some drugs also act as endocrine disruptors by exerting off-target effects on endocrine tissues. However, the mechanisms of toxicity of these compounds on male reproduction at doses compatible with human exposure are still not fully resolved, especially in the case of mixtures, which remain understudied. This review presents first an overview of the mechanisms regulating Sertoli cell development, maintenance, and functions, and then surveys what is known on the impact of EDCs and drugs on immature Sertoli cells, including individual compounds and mixtures, and pinpointing at knowledge gaps. Performing more studies on the impact of mixtures of EDCs and drugs at all ages is crucial to fully understand the adverse outcomes these chemicals may induce on the reproductive system.

Mono-(2-ethylhexyl) phthalate reversibly disrupts the blood-testis barrier in pubertal rats

“…Phthalates, a class of synthetic chemicals used in various consumer products, have been shown to exert adverse effects on SCs, which play a pivotal role in the maintenance of testicular microenvironment and sperm development. They disrupt SC function, reduce essential factor production like anti-Müllerian hormone and inhibin B, which are crucial for sperm maturation; impair structural integrity, and interfere with the endocrine signaling pathways necessary for SC function, potentially disrupting the hormonal regulation of spermatogenesis ( Corpuz-Hilsabeck and Culty, 2023 ). This disrupts male fertility, highlighting the need for more awareness and regulation of phthalate exposure.…”

The adverse role of endocrine disrupting chemicals in the reproductive system

“…These chemicals may have estrogenic, anti-estrogenic, androgenic or anti-androgenic effects, which are crucial for maintaining homeostasis, reproductive functions, development, and behavior. The increasing prevalence of human endocrine-related diseases, particularly disorders of the female and male reproductive systems, and even certain cancers (e.g., breast cancer, endometrial cancer, ovarian cancer, cervical cancer, prostate cancer, and testicular cancer), has aroused people’s attention to EDCs ( 5 – 7 ). EDCs represent a global issue of great significance for humans and the environment 8 ).…”

Functions and mechanism of noncoding RNA in regulation and differentiation of male mammalian reproduction

“…1 In the seminiferous cords that will eventually develop into the seminiferous tubules, the gonocytes start to form a strong relationship with the somatic Sertoli cells. 2 The gonocytes travel to the seminiferous tubules' basement membrane after birth, where they reenter the cell cycle to develop into undifferentiated spermatogonia or spermatogonial stem cells (SSC). 3 The "blood-testis barrier" is a junction between Sertoli cells that divides the tubules into the basal compartment, which houses the spermatogonial cell population, and the adluminal compartment, which will house the developing germ cells.…”

“…Following sexual differentiation, male germ cells are initially designated in fetal life when the primordial germ cells become gonocytes and experience a burst of mitotic growth before entering G0 arrest 1 . In the seminiferous cords that will eventually develop into the seminiferous tubules, the gonocytes start to form a strong relationship with the somatic Sertoli cells 2 . The gonocytes travel to the seminiferous tubules' basement membrane after birth, where they reenter the cell cycle to develop into undifferentiated spermatogonia or spermatogonial stem cells (SSC) 3 .…”