Transgenerational exposure to plastics-derived endocrine-disrupting bisphenol A and its analogs on male infertility: impact of gut dysbiosis and epigenetic regulation.
Basak S, Varma S, Nag S, Duttaroy A • Frontiers in endocrinology • 2026
BPA and its analogs disrupt male fertility through gut dysbiosis and epigenetic mechanisms that can be transmitted across generations, with the gut-reproductive axis playing a central role in mediating these effects.
Key Findings
Background
BPA exposure alters gut microbial composition, diversity, and metabolites, leading to dysbiosis that modulates systemic inflammation, estrogen bioavailability, and the endocrine-immune axis, thereby affecting gonadal function.
BPA exposure in vivo has been shown to alter gut microbial composition, diversity, and metabolites
Gut alterations modulate systemic inflammation, estrogen bioavailability, and the endocrine-immune axis
These changes affect gonadal function through the gut-reproductive axis
The gut is described as 'the largest endocrine organ in the body, directly regulating multiple metabolites that reach the circulation and influence the functions of peripheral organs and systems'
Background
BPA can diffuse across cell membranes and enter the nucleus, altering transcription of target genes by modifying nuclear receptor activity and gene promoter methylation, similar to the steroid hormone estradiol.
BPA mimics estradiol, a steroid hormone, in its mechanism of action
BPA modifies nuclear receptor activity and gene promoter methylation
Gene-chemical interactions result in epigenetic alterations
These mechanisms allow BPA to act as an estrogen-mimicking endocrine-disrupting chemical (EDC)
Background
BPA exposure in utero alters the epigenome, with epigenetic changes capable of being transmitted across generations as epimutation states.
In utero BPA exposure alters the epigenome, highlighting the need for transgenerational assessment
Recent evidence on fetal programming suggests bisphenol exposure events 'can also impact epimutation states beyond diet, potentially carrying across generations'
The genomic imprint is modulated by gene-chemical interactions which predominantly result in epigenetic alterations
Transgenerational transmission of these epigenetic changes represents a mechanism by which BPA exposure affects future generations
Background
Global declines in male fertility characterized by reduced sperm count, motility, and quality are associated with environmental exposures to bisphenol-based endocrine-disrupting chemicals.
The paper identifies reduced sperm count, motility, and quality as key characteristics of declining male fertility
BPA and its analogs are identified as estrogen-mimicking EDCs contributing to reproductive dysfunction
The review encompasses BPA as well as BPA analogs (bisphenol analogs) in assessing male infertility risk
The paper frames this as a global concern warranting urgent research attention
Background
Little is known about epigenetic perturbations due to exposure to plastic-derived endocrine-disrupting bisphenols and their specific role in gut dysbiosis and male infertility risks.
The authors identify a knowledge gap regarding epigenetic perturbations from bisphenol exposure in the context of gut dysbiosis and male infertility
The paper is a narrative review that conducted 'a thorough review of the available data'
The review underscores 'the importance of further research in this area'
The gut-reproductive axis is identified as a central but understudied mechanism linking bisphenol exposure to male infertility
What This Means
This research suggests that common plastics-derived chemicals known as bisphenols — particularly bisphenol A (BPA), which is found in many food containers, water bottles, and other consumer products — may contribute to declining male fertility through two key biological pathways: disruption of the gut microbiome and changes to how genes are expressed (epigenetics). When people are exposed to BPA, the chemical can mimic the hormone estrogen in the body, interfering with normal reproductive function. BPA also disturbs the community of bacteria living in the gut, which in turn affects hormone levels, immune responses, and the function of reproductive organs. These disruptions can reduce sperm count, motility, and quality.
Perhaps most concerning, this review highlights evidence that BPA exposure — especially during fetal development in the womb — can cause changes to the epigenome (the chemical tags that control which genes are turned on or off) that may be passed down to future generations. This means that a parent's or even grandparent's exposure to BPA could potentially affect the fertility of their descendants, even if those descendants were never directly exposed to high levels of the chemical themselves.
This research suggests there is an urgent need for more studies examining how BPA and related chemicals affect the gut-reproductive axis and how these effects are inherited across generations. The findings raise broader questions about the long-term public health consequences of widespread plastic use and exposure to BPA analogs that have been introduced as replacements for BPA in 'BPA-free' products, as these alternatives may carry similar risks.
Basak S, Varma S, Nag S, Duttaroy A. (2026). Transgenerational exposure to plastics-derived endocrine-disrupting bisphenol A and its analogs on male infertility: impact of gut dysbiosis and epigenetic regulation.. Frontiers in endocrinology. https://doi.org/10.3389/fendo.2026.1799472