The impact of persistent organic pollutants on fertility: exposure to the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin alters reproductive tract immune responses

Front Immunol. 2024 Dec 10:15:1497405. doi: 10.3389/fimmu.2024.1497405. eCollection 2024.

Abstract

Exposure to environmental contaminants can result in profound effects on the host immune system. One class of environmental toxicants, known as dioxins, are persistent environmental contaminants termed "forever chemicals". The archetype toxicant from this group of chemicals is 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), an immunotoxicant that activates the aryl-hydrocarbon receptor pathway leading to a variety of changes in immune cell responses. Immune cell functions are crucial to the development and maintenance of healthy reproduction. Immune cells facilitate tolerance between at the maternal-fetal interface between the parent and the semi-allogenic fetus and help defend the gravid reproductive tract from infectious assault. Epidemiological studies reveal that exposure to environmental contaminants (such as TCDD) are linked to adverse reproductive health outcomes including endometriosis, placental inflammation, and preterm birth. However, little is known about the molecular mechanisms that underpin how environmental toxicant exposures impact immune functions at the maternal-fetal interface or within the reproductive tract in general. This review presents the most recent published work that studies interactions between dioxin or TCDD exposure, the host immune system, and reproduction.

Keywords: TCDD; dioxin; environmental toxicant; innate immunity; reproduction.

Publication types

  • Review

MeSH terms

  • Animals
  • Environmental Exposure / adverse effects
  • Environmental Pollutants / toxicity
  • Female
  • Fertility* / drug effects
  • Fertility* / immunology
  • Humans
  • Immune System / drug effects
  • Immune System / immunology
  • Immune System / metabolism
  • Persistent Organic Pollutants / adverse effects
  • Persistent Organic Pollutants / immunology
  • Persistent Organic Pollutants / toxicity
  • Polychlorinated Dibenzodioxins* / toxicity
  • Pregnancy
  • Reproduction / drug effects
  • Reproduction / immunology

Substances

  • Polychlorinated Dibenzodioxins
  • Persistent Organic Pollutants
  • Environmental Pollutants

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Department of Veterans Affairs Merit Award I01BX005352 Office of Research (to JG). Additional support was provided by the National Science Foundation (NSF) NSF 2112556 (to SD), This work was also supported by the National Institutes of Health (NIH) R01HD090061, R01AI134036 (to JG), NIH F31ES034957 (VS), NIH F32HD100087 (to AE), and the Chan Zuckerberg Science Initiative (CZI) Diversity Leadership Awards (2022-253614 to SD and 2022-253529 AH), UNCF/Bristol-Myers Squibb E.E. Just Faculty Fund, Career Award at the Scientific Interface (CASI Award) from Burroughs Welcome Fund (BWF) # 1021868.01, BWF Ad-hoc Award (to AH), March of Dimes #6-FY24-0009 (to JG), and BWF Next Gen Pregnancy Initiative Award # 1275387 (to JG), NIH Small Research Pilot Subaward to 5R25HL106365-12 from the National Institutes of Health PRIDE Program, DK020593, Vanderbilt Diabetes and Research Training Center (DRTC) Alzheimer’s Disease Pilot & Feasibility Program. WA is supported by NIH training grant T32GM142518. This work was also supported by Assistance Agreement No. RD83950101 awarded by the U.S. Environmental Protection Agency (to KO). It has not been formally reviewed by EPA. This project was funded in part by the Rise-Up Summer Research Program (Office of Research and Development, Department of Veterans Affairs, I01BX007005).