In a recent review published in International Journal of Molecular Sciences, scientists discuss the effect of bisphenol A (BPA) on human male fertility.

Study: The Effects of Bisphenol A on Human Male Infertility: A Review of Current Epidemiological Studies. Image Credit: Yurchanka Siarhei / Shutterstock.com

Background

Endocrine disrupting chemicals are harmful man-made substances present in pesticides, metals, and additives or contaminants in food and private care products. These substances are able to interfering with the biosynthesis, secretion, transportation, binding, or removal of endogenous hormones. Consequently, these chemicals can have potentially damaging effects on the event, reproduction, neurological, cardiovascular, immune, and metabolism systems in each humans and animals.  

BPA is an endocrine disruptor chemical able to triggering the onset and development of varied health adversities, including infertility. This chemical is vastly used for the production of phenol resins, polyacrylics, polyesters, epoxy resins, and polycarbonate plastics.

Humans will be exposed to BPA through ingestion, inhalation, and skin contact. Orally ingested BPA is rapidly absorbed into the bloodstream across the intestine and subsequently metabolized by the liver. Throughout the liver, detoxing reactions by uridine diphosphate glucuronosyltransferase or sulfotransferases eliminate the estrogenic activity of BPA.

Free or unconjugated BPA is taken into account the energetic form with harmful endocrine disrupting effects. Over 99% of energetic BPA metabolites are excreted in feces and urine, while just one% accumulate in tissues. Unlike ingestion, BPA entering within the body through skin contact can escape hepatic metabolism, thereby leading to excessive accumulation of free BPA within the blood.      

As a result of its structural similarity to 17 beta-estradiol, BPA can bind to alpha and beta estrogen receptors to trigger estrogenic effects. BPA also can bind to G-protein-coupled estrogen, gamma peroxisome proliferator-activated, and orphan nuclear estrogen gamma receptors, thereby resulting in major cellular and endocrine disruptions.

BPA also can compete with endogenous estradiol to dam estrogen receptors, thus acting as an anti-estrogen substance. By directly binding to androgen receptors, BPA is able to blocking endogenous androgen activities.  

Effect of BPA exposure on human male fertility

BPA affects the human male reproductive system by disrupting the hypothalamic-pituitary-testicular axis and altering the expression and activity of enzymes related to testicular steroidogenesis and spermatogenesis. BPA also causes sperm damage by suppressing the antioxidant system and subsequently increasing oxidative stress.

BPA affects spermatogenesis by mimicking the activity of estradiol, thus resulting in poor sperm quality and infertility. Furthermore, BPA acts as an antagonist against the thyroid hormone receptor, which ultimately prevents the activity of thyroid hormones.

Limited and inconsistent evidence is currently available regarding the effect of BPA exposure on human male fertility. Although many studies have found as association between BPA exposure and male infertility, these studies have primarily assessed occupational and high-level exposures. All studies are observational epidemiological studies.   

Regarding occupational exposure, three studies have been conducted in Chinese populations. Overall, these studies have shown that high-level and long-term BPA exposure is related to reduced androstenedione, testosterone, and follicle-stimulating hormone (FSH) levels, in addition to increased sex hormone-binding globulin, estradiol, and prolactin levels. Taken together, these hormonal changes can potentially result in male infertility.

In a single study conducted on the overall Danish population, BPA exposure was related to increased levels of testosterone, estradiol, and luteinizing hormone (LH). One other study conducted in low-industrialized area in China reported that low-level environmental exposure to BPA is related to increased levels of LH and FSH in male smokers and decreased levels of total testosterone in chubby men. These findings suggest a task of body weight and smoking status on BPA-mediated hormonal alterations.

Regarding testicular functions, an association has been observed between higher urinary BPA levels and lower sperm motility in men carrying a filaggrin gene mutation. Similarly, increased BPA level in biological fluids has been found to extend the danger of subfertility.

Considering low-level environmental BPA exposure, one study involving fertile men couldn’t discover any significant impact on male reproductive functions. In contrast, one study involving university students suggests an association between higher urinary BPA levels and lower Leydig cell capability and sperm count. This study indicates a possible negative effect of environmental BPA exposure on the male reproductive system.

Studies conducted on men with diagnosed infertility have found associations between increased urinary BPA levels and lower sperm count, sperm concentration, sperm vitality, sperm motility, and altered sperm morphology. In contrast, some studies comparing fertile men with infertile men have shown no association between BPA exposure and infertility. Overall, these studies indicate that male infertility can’t be attributed to BPA exposure and that only high-level BPA exposure can negatively affect fertility in men.

Studies analyzing seminal BPA levels have found that increased levels of BPA in seminal plasma can reduce sperm quality and suppress testicular steroidogenesis. Studies investigating DNA methylation have identified notable associations between higher occupational BPA exposure and increased DNA hydroxymethylation, which may negatively affect male fertility.

Regarding maternal BPA exposure and male reproductive function, a weak association of prenatal BPA exposure with sperm quality and testicular functions has been observed in men later in life.

Conclusions

Most up-to-date studies investigating the impact of BPA on male fertility have identified an association between high-level occupational BPA exposure and reduced sperm quality, which could possibly be attributed to BPA-induced hormonal alterations. Nonetheless, nearly all of studies investing low-level environmental BPA exposure indicate no association between BPA exposure and male infertility.