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 found in pesticides, metals, and additives or contaminants in food and personal care products. These substances are capable of interfering with the biosynthesis, secretion, transportation, binding, or removal of endogenous hormones. As a result, these chemicals can have potentially damaging effects on the development, reproduction, neurological, cardiovascular, immune, and metabolism systems in both humans and animals.
BPA is an endocrine disruptor chemical capable of triggering the onset and development of various health adversities, including infertility. This chemical is vastly used for the production of phenol resins, polyacrylics, polyesters, epoxy resins, and polycarbonate plastics.
Humans can 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. Within the liver, detoxification reactions by uridine diphosphate glucuronosyltransferase or sulfotransferases eliminate the estrogenic activity of BPA.
Free or unconjugated BPA is considered the active form with harmful endocrine disrupting effects. Over 99% of active BPA metabolites are excreted in feces and urine, while only 1% accumulate in tissues. Unlike ingestion, BPA entering in the body through skin contact can escape hepatic metabolism, thereby resulting in excessive accumulation of free BPA in the blood.
Due to its structural similarity to 17 beta-estradiol, BPA can bind to alpha and beta estrogen receptors to trigger estrogenic effects. BPA can also bind to G-protein-coupled estrogen, gamma peroxisome proliferator-activated, and orphan nuclear estrogen gamma receptors, thereby leading to major cellular and endocrine disruptions.
BPA can also compete with endogenous estradiol to block estrogen receptors, thus acting as an anti-estrogen substance. By directly binding to androgen receptors, BPA is capable of 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 leading to poor sperm quality and infertility. Moreover, 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 associated with reduced androstenedione, testosterone, and follicle-stimulating hormone (FSH) levels, as well as increased sex hormone-binding globulin, estradiol, and prolactin levels. Taken together, these hormonal changes can potentially lead to male infertility.
In one study conducted on the general Danish population, BPA exposure was associated with increased levels of testosterone, estradiol, and luteinizing hormone (LH). Another study conducted in low-industrialized area in China reported that low-level environmental exposure to BPA is associated with increased levels of LH and FSH in male smokers and decreased levels of total testosterone in overweight men. These findings suggest a role 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 increase the risk of subfertility.
Considering low-level environmental BPA exposure, one study involving fertile men could not identify 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 capacity 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 cannot 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 can 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 recent 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 be attributed to BPA-induced hormonal alterations. However, the majority of studies investing low-level environmental BPA exposure indicate no association between BPA exposure and male infertility.
