Impact of endocrine-disrupting chemicals on steroidogenesis and consequences on testicular function


Testes, prostate, epididymis, among other organs, make up the male reproductive system. Testes are the most critical as they are the sites for steroid hormone synthesis and spermatogenesis. The ability of the testes to form steroids, also known as testicular steroidogenesis, promotes the production of androgens essential for the development and functioning of the male reproductive system. Also, these androgens are necessary for male health and general well-being. However, disruptions in testicular steroidogenesis can result in reproduction system dysfunction, abnormalities, and infertility.

The male reproductive system requires sex hormones for its development and functioning. This inadvertently renders it a target of the endocrine-disrupting chemicals since most affect estrogen and androgen production and signaling. While fetal testis is dedicated to the growth and development of the male reproductive tissues, the adult testis is dedicated to the production of spermatozoa, androgen, along with other tissues. The processes demand an efficiently regulated hormonal function. Therefore, subtle disturbances by endocrine-disrupting chemicals can severely impact testicular development and function.

Leydig cells produce steroidogenic enzymes needed for the production of estrogen, testis development, male genitalia development, and reproductive function. Leydig cells synthesize androgen through steroidogenesis, which involves converting cholesterol into derivatives such as androgens. Leydig cells are also responsible for testosterone biosynthesis and other estrogens and androgen production, including estradiol, estrone, and 5α-dihydrotestosterone (DHT).

Endocrine-disrupting chemicals are ubiquitously found in the environment and are a part of the products we consume each day. Several toxicology studies focusing on the effect of these chemicals on human testicular function are performed using exposures to a single endocrine-disrupting chemical at doses exceeding human exposure levels. Therefore, investigating the risks that would come with exposures to endocrine-disrupting chemical mixtures at low doses is still needed.

In light of this, researchers Casandra Walker, Samuel Garza, Vassilios Papadopoulos, and Martine Culty of the University of Southern California, Unites States, presented a study on endocrine-disrupting chemical mixtures and their effects on testicular function. Their study also entailed revelations of the antiandrogenic impacts of endocrine-disrupting chemical mixtures on testicular function and fertility. Their research work is published in the journal Molecular and Cellular Endocrinology.

Endocrine-disrupting chemicals (EDCs) have anti-estrogenic and antiandrogenic properties. Therefore, they have the potential to affect Leydig cells’ development and function and steroidogenesis negatively. For this reason, EDCs can either be defined as an exogenous chemical or a chemical mixture that disrupts hormone action. They include phthalates, bisphenols, paraben, and perfluoroalkyl. The male reproductive system is a victim of EDCs’ antiandrogenic activity because of its unique requirement of precise proportions of estrogens and androgens.

In this study, the authors investigated the effects of genistein mixed with either mono(2-Ethylhexyl) phthalate (MEHP) in vitro or 2-(diethylhexyl phthalate) (DEHP) in vivo. They reported that genistein and DEHP mixture disrupted gene and Leydig protein expression in rat testis. The researchers observed adult testosterone levels to decrease significantly with a lower genistein-DEHP mixture. Taken together, these findings suggest that low EDC mixture doses are enough to affect testicular steroidogenesis severely. They also indicate that DEHP, genistein, and their mixture distinctively affect estrogen and androgen production.

The authors used DEHP and genistein as an endocrine-disrupting chemical prototype at doses similar to human exposure doses. They observed that the mixture had adverse effects on the testis than had been with single EDCs in previous studies. In an earlier study by the authors, exposures of genistein, DEHP, or their mixtures in 0.1 and 10mg/kg/day increased infertility incidences and atrophied testis morphology.

Taken together, the findings of this study form a basis for further determining the effects of EDCs and their mixtures on the male reproductive system.


Casandra Walker, Samuel Garza, Vassilios Papadopoulos, and Martine Culty. Impact of endocrine-disrupting chemicals on steroidogenesis and consequences on testicular function. Molecular and Cellular Endocrinology, 527 (2021) 111215.

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