Prenatal Exposure to Environmentally-Relevant Contaminants Perturbs Male Reproductive Parameters Across Multiple Generations that are Partially Protected by Folic Acid Supplementation

Sci Rep. 2019 Sep 25;9(1):13829. doi: 10.1038/s41598-019-50060-z.


The paternal environment is thought to influence sperm quality and future progeny may also be impacted. We hypothesized that prenatal exposure to environmentally-relevant contaminants impairs male reproduction, altering embryo gene expression over multiple generations. Folic acid (FA) can improve sperm quality and pregnancy outcomes, thus we further hypothesized that FA mitigates the contaminants. Sprague-Dawley F0 female rats treated with persistent organic pollutants (POPs) or corn oil and fed basal or supplemented FA diets, then used to yield four generations of litters. Only F0 females received POPs and/or FA treatments. In utero POPs exposure altered sperm parameters in F1, which were partly rescued by FA supplementation. Paternal exposure to POPs reduced sperm quality in F2 males, and the fertility of F3 males was modified by both POPs and FA. Ancestral FA supplementation improved sperm parameters of F4 males, while the POPs effect diminished. Intriguingly, F3 males had the poorest pregnancy outcomes and generated the embryos with the most significantly differentially expressed genes. Early-life exposure to POPs harms male reproduction across multiple generations. FA supplementation partly mitigated the impact of POPs. The two-cell embryo transcriptome is susceptible to paternal environment and could be the foundation for later pregnancy outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Environmental Pollution / adverse effects*
  • Female
  • Folic Acid / administration & dosage*
  • Folic Acid / pharmacology
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental / drug effects
  • Male
  • Paternal Exposure / adverse effects
  • Pregnancy
  • Prenatal Exposure Delayed Effects / diet therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Reproduction / drug effects*
  • Spermatozoa / drug effects*


  • Folic Acid

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