Abstract
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.
Highlights
The paternal environment is thought to influence sperm quality and future progeny may be impacted
Testicular spermatid count is lower in the F2 generation for rats sired by F1 fathers whose germ cells were directly exposed to persistent organic pollutants (POPs) in utero through F0 females’ exposure (p = 0.01)
When the F2 rats were not exposed to POPs, Folic acid (FA) supplementation decreased normal sperm morphology
Summary
The paternal environment is thought to influence sperm quality and future progeny may 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, we further hypothesized that FA mitigates the contaminants. Levels of persistent organic pollutants (POPs), including polychlorinated biphenyls (PCBs) and legacy pesticides such as dichlorodiphenyltrichloroethane (DDT) have been declining since their use was restricted by the Stockholm Convention in 20011 Due to their long half-life and lipophilic nature, they remain present in the environment[2]. Men with reduced sperm quality have a shorter life expectancy[8] and have a higher risk of adverse health outcomes such as cardiovascular disease, hypertension and diabetes[6,7]. In Canada, and many other countries, higher folic acid intake is ensured by mandatory fortification of white wheat flour and other enriched grain products[20] Folic acid deficiency in mouse models reduces sperm function and sperm count[21,22,23] and supplementation could protect the father’s sperm from the adverse effects of environmental contaminants[24]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
