Paternal Environmental Toxicant Exposure and Risk of Adverse Pregnancy Outcomes
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Purpose of Review
Current clinical efforts to predict and prevent preterm birth are primarily focused on the mother and have made minimal progress in improving outcomes. However, recent data indicate that paternal factors can also influence timing of birth. Herein, we will review recent human and murine data examining the contribution of the father to pregnancy outcomes with an emphasis on environmental exposures that can negatively impact fertility and the timing of birth.
Human epidemiology studies now clearly indicate that a variety of paternal factors (age, race, weight, smoking status) can influence sperm quality, birth timing and, in some studies, offspring health. Utilizing a mouse model, our data have demonstrated that developmental exposure of the male to the environmental toxicant TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is associated with a transgenerational reduction in sperm number and quality and an increased risk of preterm birth in an unexposed partner.
Toxicant exposure history can clearly influence sperm quality in men and mice. Murine data further indicate that exposures which negatively affect sperm quality also impair placental function, potentially leading to preterm birth and other adverse outcomes. Of particular concern, these changes have been linked to epigenetic alterations within the male germ cell which can then be transmitted across multiple generations. Since it is not possible to prevent an ancestral toxicant exposure in a human population, identifying lifestyle modifications that can be implemented during the preconception period to improve sperm quality should be explored for the therapeutic potential to reduce the incidence of PTB and its sequelae.
KeywordsPreterm birth TCDD Human Murine Muti-generational Transgenerational
We gratefully acknowledge the assistance of Ms. Evelyn Hipp for contributing her artistic talent to Fig. 1.
Studies presented herein were supported in part by VA I01 BX002853, NIEHS ES14942, Amag Pharmaceuticals and the Vanderbilt University School of Medicine Medical Scholars Program.
Compliance with Ethical Standards
Conflict of Interest
Shilpa Mokshagundam, Alison Barlow, and Tianbing Ding declare no conflict of interest. Kaylon L. Bruner-Tran reports grants from National Institute of Environmental Health Science, the Department of Veteran Affairs, the Environmental Protection Agency, and from AMAG Pharmacueticals, during the conduct of the study. Kevin G. Osteen reports grants from Gates Foundation, the Environmental Protection Agency, the National Institute of Environmental Health Science, and from the Department of Veteran Affairs, during the conduct of the study.
Human and Animal Rights and Informed Consent
This article does not contain any new studies with humans or animals subjects performed by the any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance
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