The incidence of metabolic disorders like type 2 diabetes and obesity continues to increase. In addition to the well-known contributors to these disorders, such as food intake and sedentary lifestyle, recent research in the exposure science discipline provides evidence that exposure to endocrine-disrupting chemicals like bisphenol A and phthalates via multiple routes (e.g., food, drink, skin contact) also contribute to the increased risk of metabolic disorders. Endocrine-disrupting chemicals (EDCs) can disrupt any aspect of hormone action. It is becoming increasingly clear that EDCs not only affect endocrine function but also adversely affect immune system function. In this review, we focus on human, animal, and in vitro studies that demonstrate EDC exposure induces dysfunction of the immune system, which, in turn, has detrimental effects on metabolic health. These findings highlight how the immune system is emerging as a novel player by which EDCs may mediate their effects on metabolic health. We also discuss studies highlighting mechanisms by which EDCs affect the immune system. Finally, we consider that a better understanding of the immunomodulatory roles of EDCs will provide clues to enhance metabolic function and contribute toward the long-term goal of reducing the burden of environmentally induced diabetes and obesity.
PMID 29145569 29145569 DOI 10.1210/en.2017-00882 10.1210/en.2017-00882 Bansal et al. 2017, Bansal 2017
Cite this article
Bansal, A., Henao‐Mejia, J., & Simmons, R. (2018). Immune System: An Emerging Player in Mediating Effects of Endocrine Disruptors on Metabolic Health. Endocrinology, 159(1), 32-45. https://doi.org/10.1210/en.2017-00882
Bansal A, Henao‐Mejia J, Simmons R. Immune System: An Emerging Player in Mediating Effects of Endocrine Disruptors on Metabolic Health. Endocrinology. 2018;159(1):32-45. doi:10.1210/en.2017-00882
Bansal, Amita, et al. "Immune System: An Emerging Player in Mediating Effects of Endocrine Disruptors on Metabolic Health." Endocrinology, vol. 159, no. 1, 2018, pp. 32-45.
Endocrine-disrupting chemicals are known to interfere with normal reproductive function and hormone signaling. Phthalates, bisphenol A, pesticides, and environmental contaminants such as polychlorinated biphenyls and dioxins are known endocrine-disrupting chemicals that have been shown to negatively affect both male and female reproduction. Exposure to these chemicals occurs on a daily basis owing to these compounds being found in plastics, personal care products, and pesticides. Recently, studies have shown that these chemicals may cause transgenerational effects on reproduction in both males and females. This is of concern because exposure to these chemicals prenatally or during adult life can negatively impact the reproductive health of future generations. This mini-review summarizes the endocrine-disrupting chemicals that humans are exposed to on a daily basis and what is known about the transgenerational effects that these chemicals may have on male and female reproduction.
Bisphenol A (BPA) is an endocrine disruptor, and exposure to low doses in utero has been associated with the development of metabolic diseases. Previous studies have suggested that bone marrow (BM) may be particularly susceptible to BPA exposure.
Here, we investigate how developmental exposure to low levels of BPA affects the BM transcriptome and the blood metabolic profile in Fischer 344 rats later in life. We compare these effects to those observed in human metabolic syndrome (MetS) using a population-based cohort.
The results show an unexpectedly extensive sex-biased effect on the BM transcriptome from a BPA dose approximately eight times lower than the recent temporary European Food Safety Authority (EFSA) human tolerable daily intake (TDI) and a higher dose considered safe in 2015. BPA exposure induces sex-specific changes in gene expression, progressing toward a hypometabolic cancer-like state in females and a hypermetabolic autoimmunity-like state in males, with a blood metabolic profile that significantly overlaps with human MetS in a cross-sectional study.
We conclude that developmental low-dose BPA exposure might induce metabolic syndrome specifically in males, possibly by affecting T cell activity in a sex-specific manner. Our study provides biologically plausible and convincing evidence for significant effects from low-dose BPA exposure, supporting the substantial lowering of the human BPA TDI by EFSA based on its critical effects on T cells.
Prada D et al., 2025·Environmental health : a global access science source
Acetaminophen is the most commonly used over-the-counter pain and fever medication taken during pregnancy, with > 50% of pregnant women using acetaminophen worldwide. Numerous well-designed studies have indicated that pregnant mothers exposed to acetaminophen have children diagnosed with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), at higher rates than children of pregnant mothers who were not exposed to acetaminophen. We applied the Navigation Guide methodology to the scientific literature to comprehensively and objectively examine the association between prenatal acetaminophen exposure and NDDs and related symptomology in offspring. We conducted a systematic PubMed search through February 25, 2025, using predefined inclusion criteria and rated studies based on risk of bias and strength of evidence. Due to substantial heterogeneity, we opted for a qualitative synthesis, consistent with the Navigation Guide's focus on environmental health evidence. We identified 46 studies for inclusion in our analysis. Of these, 27 studies reported positive associations (significant links to NDDs), 9 showed null associations (no significant link), and 4 indicated negative associations (protective effects). Higher-quality studies were more likely to show positive associations. Overall, the majority of the studies reported positive associations of prenatal acetaminophen use with ADHD, ASD, or NDDs in offspring, with risk-of-bias and strength-of-evidence ratings informing the overall synthesis. Our analyses using the Navigation Guide thus support evidence consistent with an association between acetaminophen exposure during pregnancy and increased incidence of NDDs. Appropriate and immediate steps should be taken to advise pregnant women to limit acetaminophen consumption to protect their offspring's neurodevelopment.
Johnson J et al., 2025·Journal of Assisted Reproduction and Genetics
The human placenta plays an important role in pregnancy and offspring health. The paternal genome contributes significantly to placental growth and development. While the maternal factors affecting gestational health are thoroughly investigated, the paternal factors are often overlooked. Thus, it is important to understand various paternal factors affecting placental development and function. To assess the effect of various paternal factors on placental development, function, and pregnancy-related disorders. This review was registered in PROSPERO (Registration number CRD420250634649). Literatures across databases like JSTOR, Scopus, Google Scholar, ScienceDirect, and PubMed were screened through a set of criteria. Forty-eight studies were selected that included low-to-moderate risk paternal factors like age, smoking, race/ethnicity/location, genetic, epigenetic factors, exposure to chemicals, seminal plasma, and lifestyle factors. Increased paternal age was reported to contribute towards higher risks of preeclampsia, spontaneous abortions, preterm birth, stillbirth, and higher placental and fetal birth weight. Paternal smoking, on the other hand, was found to be an associated risk factor for placental abruption and stillbirth. Exposure to various chemicals was found to be associated with changes in sperm epigenome and placental dysfunction. Discussion and Paternal health, lifestyle, and exposure to chemicals may affect placental development and pregnancy. Paternal factors may alter seminal plasma proteome, cytokine profile, and abnormal sperm DNA methylation of imprinted genes which is associated with adverse pregnancy outcomes. Pre-conceptional health assessment of prospective fathers might be helpful in ensuring optimal placental development in pregnancies to follow, in addition to newborn health.