Potential Mechanisms of Bisphenol A (BPA) Contributing to Human Disease

Bisphenol A (BPA) is an organic synthetic compound serving as a monomer to produce polycarbonate plastic, widely used in the packaging for food and drinks, medical devices, thermal paper, and dental materials. BPA can contaminate food, beverage, air, and soil. It accumulates in several human tissues and organs and is potentially harmful to human health through different molecular mechanisms. Due to its hormone-like properties, BPA may bind to estrogen receptors, thereby affecting both body weight and tumorigenesis. BPA may also affect metabolism and cancer progression, by interacting with GPR30, and may impair male reproductive function, by binding to androgen receptors. Several transcription factors, including PPARγ, C/EBP, Nrf2, HOX, and HAND2, are involved in BPA action on fat and liver homeostasis, the cardiovascular system, and cancer. Finally, epigenetic changes, such as DNA methylation, histones modification, and changes in microRNAs expression contribute to BPA pathological effects. This review aims to provide an extensive and comprehensive analysis of the most recent evidence about the potential mechanisms by which BPA affects human health.

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Adverse Effects of Bisphenol A on Male Reproductive Function

Reviews of Environmental Contamination and Toxicology - Reviews of Environmental Contamination and Toxicology Volume 228 ◽

10.1007/978-3-319-01619-1_3 ◽

2013 ◽

pp. 57-82 ◽

Cited By ~ 19

Author(s):

Faustin Pascal Tsagué Manfo ◽

Rajamanickam Jubendradass ◽

Edouard Akono Nantia ◽

Paul Fewou Moundipa ◽

Premendu Prakash Mathur

Keyword(s):

Adverse Effects ◽

Bisphenol A ◽

Reproductive Function ◽

Male Reproductive Function

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Bisphenol A differentially affects male reproductive function biomarkers in a reference population and agro pesticides users from Djutitsa, Cameroon

Toxicology and Industrial Health ◽

10.1177/0748233719838437 ◽

2019 ◽

Vol 35 (4) ◽

pp. 324-335 ◽

Cited By ~ 2

Author(s):

Faustin Pascal Tsagué Manfo ◽

Cathérine Harthé ◽

Edouard Akono Nantia ◽

Henri Dechaud ◽

Angèle Nkouatchoua Tchana ◽

...

Keyword(s):

Bisphenol A ◽

Daily Intake ◽

Reproductive Function ◽

Reference Population ◽

Average Concentration ◽

Sex Hormone Binding Globulin ◽

Urinary Concentration ◽

Total Testosterone ◽

Male Reproductive Function ◽

Significant Difference

The consequences of bisphenol A (BPA) exposure on male reproductive function were studied in two populations from Cameroon, farmers using agro pesticides in Djutitsa (rural area) and townsmen in Yaoundé (urban area, Centre region). Urinary BPA concentration from all participants was measured, and the values were correlated with biochemical markers of male reproductive function. The data showed that BPA could be detected in 92.6% of urine participants, with an average concentration of 2.18 ± 1.97 µg/g creatinine but with no significant difference between the urinary BPA concentration from rural and urban populations. From BPA urinary concentration, the BPA average daily intake was estimated to be 0.06 ± 0.05 μg/kg/day (3.51 µg/day per individual) in the Cameroon population. Interestingly, free and bioavailable testosterone concentrations and estradiol/testosterone ratio correlated with BPA levels in the overall population. When data were analysed according to residence, BPA correlated with total testosterone levels ( r = −0.433) and estradiol/testosterone ratio ( r = 0.338) in the urban residents only, while the rural population exhibited significant increases in sex-hormone-binding globulin with increased BPA exposure. Our data showed that the male Cameroon population is exposed to BPA but that inconstant BPA association to endocrine reproductive markers suggests that other environmental factors in combination with BPA exposure might influence testicular function.

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The Impact of Prenatal Exposure to Bisphenol A on Male Reproductive Function

Frontiers in Endocrinology ◽

10.3389/fendo.2020.00320 ◽

2020 ◽

Vol 11 ◽

Author(s):

Roger J. Hart

Keyword(s):

Bisphenol A ◽

Prenatal Exposure ◽

Reproductive Function ◽

Male Reproductive Function ◽

The Impact

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Effects of exposure to a “safe” dose of bisphenol A on male reproductive function and the paternal contribution to the hypothalamic transcriptome profile

Chemosphere ◽

10.1016/j.chemosphere.2020.127447 ◽

2020 ◽

Vol 259 ◽

pp. 127447

Author(s):

Nannan Wu ◽

Xianneng Li ◽

Fangyi Xu ◽

Chong Tian ◽

Shuiqing He ◽

...

Keyword(s):

Bisphenol A ◽

Reproductive Function ◽

Transcriptome Profile ◽

Male Reproductive Function ◽

Paternal Contribution ◽

Safe Dose

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Association of Bisphenol A Exposure with LINE-1 Hydroxymethylation in Human Semen

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph15081770 ◽

2018 ◽

Vol 15 (8) ◽

pp. 1770 ◽

Cited By ~ 7

Author(s):

Youping Tian ◽

Xiaoyu Zhou ◽

Maohua Miao ◽

De-kun Li ◽

Ziliang Wang ◽

...

Keyword(s):

Bisphenol A ◽

Reproductive Function ◽

Exposed Group ◽

Human Semen ◽

Linear Regression Models ◽

Endocrine Disrupting Chemical ◽

Dna Hydroxymethylation ◽

Unexposed Group ◽

Male Reproductive Function ◽

Male Workers

Bisphenol A (BPA), an exogenous endocrine-disrupting chemical, has been shown to alter DNA methylation. However, little information is available about the effect of BPA exposure on DNA hydroxymethylation in humans. The objective of the present study was to examine whether BPA exposure was associated with DNA hydroxymethylation in human semen samples. We measured urine BPA levels and LINE-1 hydroxymethylation in 158 male factory workers selected from an occupational cohort study conducted in China between 2004 and 2008. Among them, there were 72 male workers with occupational BPA exposure (BPA-exposed group) and 86 male workers without occupational BPA exposure (unexposed group). Multivariate linear regression models were used to examine the association of exposure to BPA with LINE-1 hydroxymethylation. LINE-1 was more highly hydroxymethylated in the BPA-exposed group than in the unexposed group (median 12.97% vs. 9.68%, respectively; p < 0.05), after adjusting for the potential confounders. The medians of 5-hydroxymethylcytosine (5hmC) generally increased with increasing urine BPA levels: 8.79%, 12.16%, 11.53%, and 13.45%, for undetected BPA and corresponding tertiles for the detected BPA, respectively. After analysis using data at individual level, our findings indicated that BPA exposure was associated with alterations of sperm LINE-1 hydroxymethylation, which might have implications for understanding the mechanisms underlying BPA-induced adverse effects on male reproductive function.

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Obesity and Male Reproduction: Do Sirtuins Play a Role?

International Journal of Molecular Sciences ◽

10.3390/ijms23020973 ◽

2022 ◽

Vol 23 (2) ◽

pp. 973

Author(s):

Federica Barbagallo ◽

Sandro La La Vignera ◽

Rossella Cannarella ◽

Laura M. Mongioì ◽

Vincenzo Garofalo ◽

...

Keyword(s):

Male Fertility ◽

Molecular Mechanisms ◽

Sperm Quality ◽

Public Health Problem ◽

Reproductive Function ◽

Male Reproduction ◽

Current Evidence ◽

Gonadal Function ◽

Male Reproductive Function

Obesity is a major current public health problem of global significance. A progressive sperm quality decline, and a decline in male fertility, have been reported in recent decades. Several studies have reported a strict relationship between obesity and male reproductive dysfunction. Among the many mechanisms by which obesity impairs male gonadal function, sirtuins (SIRTs) have an emerging role. SIRTs are highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that play a role in gene regulation, metabolism, aging, and cancer. SIRTs regulate the energy balance, the lipid balance, glucose metabolism, and adipogenesis, but current evidence also indicates a role for SIRTs in male reproduction. However, the majority of the studies have been conducted in animal models and very few have been conducted with humans. This review shows that SIRTs play an important role among the molecular mechanisms by which obesity interferes with male fertility. This highlights the need to deepen this relationship. It will be of particular interest to evaluate whether synthetic and/or natural compounds capable of modifying the activity of SIRTs may also be useful for the treatment of obesity and its effects on gonadal function. Although few studies have explored the role of SIRT activators in obesity-induced male infertility, some molecules, such as resveratrol, appear to be effective in modulating SIRT activity, as well as counteracting the negative effects of obesity on male fertility. The search for strategies to improve male reproductive function in overweight/obese patients is a challenge and understanding the role of SIRTs and their activators may open new interesting scenarios in the coming years.

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Insights into leptin signaling and male reproductive health: the missing link between overweight and subfertility?

Biochemical Journal ◽

10.1042/bcj20180631 ◽

2018 ◽

Vol 475 (22) ◽

pp. 3535-3560 ◽

Cited By ~ 7

Author(s):

Bruno P. Moreira ◽

Mariana P. Monteiro ◽

Mário Sousa ◽

Pedro F. Oliveira ◽

Marco G. Alves

Keyword(s):

Reproductive Health ◽

Molecular Mechanisms ◽

Sperm Count ◽

Reproductive Function ◽

Reproductive Age ◽

Male Factor ◽

Leptin Signaling ◽

Male Reproductive Function ◽

Downward Spiral ◽

Male Reproductive Health

Obesity stands as one of the greatest healthcare challenges of the 21st century. Obesity in reproductive-age men is ever more frequent and is reaching upsetting levels. At the same time, fertility has taken an inverse direction and is decreasing, leading to an increased demand for fertility treatments. In half of infertile couples, there is a male factor alone or combined with a female factor. Furthermore, male fertility parameters such as sperm count and concentration went on a downward spiral during the last few decades and are now approaching the minimum levels established to achieve successful fertilization. Hence, the hypothesis that obesity and deleterious effects in male reproductive health, as reflected in deterioration of sperm parameters, are somehow related is tempting. Most often, overweight and obese individuals present leptin levels directly proportional to the increased fat mass. Leptin, besides the well-described central hypothalamic effects, also acts in several peripheral organs, including the testes, thus highlighting a possible regulatory role in male reproductive function. In the last years, research focusing on leptin effects in male reproductive function has unveiled additional roles and molecular mechanisms of action for this hormone at the testicular level. Herein, we summarize the novel molecular signals linking metabolism and male reproductive function with a focus on leptin signaling, mitochondria and relevant pathways for the nutritional support of spermatogenesis.

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