Environmental Contributors to Infertility

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Topic Description

Post Date: July 20, 2026

Expiration Date: June 11, 2028

Environmental exposures have been linked to infertility in males and females, including longer time to conception and pregnancy loss. Environment is defined as exposure to hazardous physical, chemical, and biological agents and stressors that adversely affect human health and reproductive function. This topic investigates the impact of these exposures on fertility and reproductive health and supports the development of tools to identify and mitigate risk.

Exposures have also been associated with declining male fertility by impairing sperm count, quality, hormonal balance, and genetic integrity. Endometriosis, polyendocrine metabolic ovarian syndrome (PMOS) [formerly known as polycystic ovary syndrome (PCOS)], and uterine fibroids are common female-specific conditions linked to environmental and endocrine-disrupting exposures. Together, these conditions impair fertility through effects on germ cell quality, implantation, and reproductive tract function, and should be explicitly considered in mechanistic and exposure-based studies.

Fundamental Mechanisms of Environmental Influence on Reproduction

  • Identify core molecular and cellular pathways by which exposures disrupt reproductive function
  • Elucidate signaling networks regulating gametogenesis, fertilization, and early development
  • Investigate endocrine disruption in estrogenic, androgenic, thyroid, and steroidogenic pathways
  • Define roles of mitochondrial function, metabolism, oxidative stress, inflammation, and DNA damage in reproductive tissues

Epigenetics and Small RNAs

  • Define how exposures alter DNA methylation, histone modifications, chromatin structure, meiosis, and nuclear architecture
  • Investigate roles of small non-coding RNAs (e.g., microRNAs, piRNAs, tRNA fragments, lncRNAs) in regulating germ cell development
  • Examine mechanisms of epigenetic inheritance
  • Develop and apply single-cell, spatial, and multi-omic approaches

New Approach Methodologies (NAMs) and Complementary Approaches

  • Develop organoids and organ-on-chip systems
  • Apply artificial intelligence/machine learning and computational toxicology
  • Integrate in vitro to in vivo extrapolation and systems models
  • Combine experimental, computational, and epidemiological data

Exposure Science and Population Studies

  • Improve measurement of chemical exposures relevant to fertility
  • Integrate exposomics and biomonitoring
  • Identify molecular signatures of exposure and reproductive effect

Extracellular Vesicles (EV) and Cellular Communication

  • Investigate roles of EV and EV cargo in reproductive tract tissue communication
  • Examine EV signaling in sperm maturation and oocyte quality, and embryo development

Assisted Reproductive Technologies (ART)

  • Evaluate embryo susceptibility to environmental stressors in vitro
  • Identify molecular signatures predicting ART success in exposed population

Life course approaches in people without known subfertility 

  • Examine windows of susceptibility impacting fertility, time to conception, and multigenerational effects

Participating ICOs

National Institute of Environmental Health Sciences (NIEHS)

Topics of interest include, but are not limited to:

  • Known (e.g., pesticides/herbicides) and emerging (e.g., mico/nanoplastics) environmental exposures with potential fertility relevance.
  • Characterization of environmental exposures and molecular signatures in fertility-relevant biological samples (e.g., seminal fluid, menstrual effluent, follicular fluid)
  • Systemic effects of environmental exposures and adverse outcomes pathways that impact fertility.
  • Fertility/fecundity as an outcome of interest in quantitative exposomics research (e.g., leveraging mass-spec approaches).
  • Development of interventions (e.g., dietary/behavioral modification) to mitigate environmental exposures prior to pregnancy and improve reproductive outcomes.

The NIEHS Worker Training Program does not participate in this topic.

IC may dedicate funds available to support applications in this Topic area depending upon the availability of funds, the number of meritorious applications, and competing ICO priorities.
IC may give special consideration to support meritorious applications in this topic area.
ICO Scientific Contact:
Thad Schug
[email protected]

Abee Boyles
[email protected]

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
IC may give special consideration to support meritorious applications in this topic area.
ICO Scientific Contact:
Susan Taymans, PhD
[email protected]

National Institute of General Medical Sciences (NIGMS)

NIGMS is interested in applications that use environmental influences on fertility and reproductive tract function to advance fundamental understanding of biological processes. NIGMS supports studies of core molecular, cellular, and genetic mechanisms such as signaling pathways, metabolism, genome regulation, and cell–cell communication that mediate responses to environmental exposures and govern gametogenesis, meiosis and fertilization.

  • Mechanistic studies of how environmental exposures affect DNA damage and basic enzymology of DNA repair processes relevant to reproductive function
  • The roles of specific genes in susceptibility to mutagenesis that impact fertility and reproductive tract biology
  • Systems level, multi-omic and computational approaches to characterize mechanisms of cellular toxicity, adaptation, and susceptibility associated with environmental perturbations
ICO Scientific Contact:
Linda Macarthur
[email protected]

Office of Research on Women's Health (ORWH)

The Office of Research on Women’s Health (ORWH) is interested in advancing research that applies sex as a biological variable to uncover mechanistic pathways through which environmental and physiological factors contribute to infertility. 

Priority areas include:

  • Elucidating the roles of hormonal disruption, oxidative stress, inflammation, epigenetic modification, and gamete toxicity
  • Defining mechanistic links between exposures and implantation failure
  • Identifying critical vulnerability windows for oocytes and sperm
  • Clarifying impacts on ovarian reserve and testicular function. 

Emerging new approach methodologies enable more precise sex‑specific modeling and accelerate translation.

The Office of Autoimmune Disease Research in ORWH (OADR-ORWH) is interested in research on: 

  • Autoimmune diseases associated with infertility, e.g., autoimmune oophoritis and orchitis, celiac disease, systemic lupus erythematosus, autoimmune endocrinopathies, antiphospholipid syndrome, and endometriosis.
This office does not award grants. Applications must be relevant to the objectives of at least one of the participating Institutes or Centers listed in this topic.
ICO Scientific Contact:
Regine A. Douthard, M.D., M.P.H
[email protected]

Victoria Shanmugam, MBBS, FRCP, FACR, CCD
[email protected]

Tribal Health Research Office (THRO)

The Tribal health Research Office (THRO) is interested in supporting research across the life course to understand how environmental exposures affect reproductive health in American Indian and Alaska Native (AI/AN) individuals. Projects may involve any type of environmental exposure(s) and investigate any aspect(s) of Native fertility and reproductive function. Studies are encouraged that explore Tribe- and community-specific exposures and potential relationships to reproductive health issues or disparities. Tribal exposure priorities should be respected. Research should be culturally grounded and involve AI/AN communities and practices as much as possible.

ICO Scientific Contact:
Sheila Caldwell, PhD
[email protected]

Christopher Barnhart, PhD
[email protected]

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