PMID- 31554827 OWN - NLM STAT- MEDLINE DCOM- 20201029 LR - 20210110 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 9 IP - 1 DP - 2019 Sep 25 TI - Prenatal Exposure to Environmentally-Relevant Contaminants Perturbs Male Reproductive Parameters Across Multiple Generations that are Partially Protected by Folic Acid Supplementation. PG - 13829 LID - 10.1038/s41598-019-50060-z [doi] LID - 13829 AB - 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. FAU - Lessard, Maryse AU - Lessard M AD - Department of Animal Sciences, Faculty of Agricultural and Food Sciences, Centre de recherche en reproduction, developpement et sante intergenerationnelle, Laval University, Quebec City, Quebec, Canada. FAU - Herst, Pauline M AU - Herst PM AD - Department of Animal Sciences, Faculty of Agricultural and Food Sciences, Centre de recherche en reproduction, developpement et sante intergenerationnelle, Laval University, Quebec City, Quebec, Canada. FAU - Charest, Phanie L AU - Charest PL AD - Department of Animal Sciences, Faculty of Agricultural and Food Sciences, Centre de recherche en reproduction, developpement et sante intergenerationnelle, Laval University, Quebec City, Quebec, Canada. FAU - Navarro, Pauline AU - Navarro P AD - Department of Nutrition, Faculty of Agricultural and Food Sciences, Centre de recherche en reproduction, developpement et sante intergenerationnelle, Laval University, Quebec City, Quebec, Canada. FAU - Joly-Beauparlant, Charles AU - Joly-Beauparlant C AD - Computational Biology Laboratory Research Centre, Faculty of Medicine, Laval University, Quebec City, Quebec, Canada. FAU - Droit, Arnaud AU - Droit A AD - Computational Biology Laboratory Research Centre, Faculty of Medicine, Laval University, Quebec City, Quebec, Canada. FAU - Kimmins, Sarah AU - Kimmins S AD - Department of Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Montreal, Quebec, Canada. AD - Department of Animal Science, Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, Quebec, Canada. FAU - Trasler, Jacquetta AU - Trasler J AD - Departments of Pediatrics, Human Genetics and Pharmacology & Therapeutics, McGill University, Research Institute, McGill University Health Centre, Montreal, Quebec, Canada. FAU - Benoit-Biancamano, Marie-Odile AU - Benoit-Biancamano MO AUID- ORCID: 0000-0003-0244-1179 AD - Department of Pathology and Microbiology, Faculty of Veterinary Medicine, University of Montreal, Saint-Hyacinthe, Quebec, Canada. FAU - MacFarlane, Amanda J AU - MacFarlane AJ AD - Nutrition Research Division, Health Canada, Ottawa, Canada. FAU - Dalvai, Mathieu AU - Dalvai M AD - Department of Animal Sciences, Faculty of Agricultural and Food Sciences, Centre de recherche en reproduction, developpement et sante intergenerationnelle, Laval University, Quebec City, Quebec, Canada. FAU - Bailey, Janice L AU - Bailey JL AUID- ORCID: 0000-0002-5490-6946 AD - Department of Animal Sciences, Faculty of Agricultural and Food Sciences, Centre de recherche en reproduction, developpement et sante intergenerationnelle, Laval University, Quebec City, Quebec, Canada. Janice.Bailey@fsaa.ulaval.ca. LA - eng GR - TE1 138294/CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190925 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 935E97BOY8 (Folic Acid) SB - IM MH - Animals MH - Disease Models, Animal MH - Environmental Pollution/*adverse effects MH - Female MH - Folic Acid/*administration & dosage/pharmacology MH - Gene Expression Profiling MH - Gene Expression Regulation, Developmental/drug effects MH - Male MH - Paternal Exposure/adverse effects MH - Pregnancy MH - Prenatal Exposure Delayed Effects/*diet therapy MH - Rats MH - Rats, Sprague-Dawley MH - Reproduction/*drug effects MH - Spermatozoa/*drug effects PMC - PMC6761122 COIS- The authors declare no competing interests. EDAT- 2019/09/27 06:00 MHDA- 2020/10/30 06:00 PMCR- 2019/09/25 CRDT- 2019/09/27 06:00 PHST- 2019/06/07 00:00 [received] PHST- 2019/08/23 00:00 [accepted] PHST- 2019/09/27 06:00 [entrez] PHST- 2019/09/27 06:00 [pubmed] PHST- 2020/10/30 06:00 [medline] PHST- 2019/09/25 00:00 [pmc-release] AID - 10.1038/s41598-019-50060-z [pii] AID - 50060 [pii] AID - 10.1038/s41598-019-50060-z [doi] PST - epublish SO - Sci Rep. 2019 Sep 25;9(1):13829. doi: 10.1038/s41598-019-50060-z.