Paternal preconception phthalate exposure alters sperm methylome and embryonic programming
Preconception environmental conditions have been demonstrated to shape sperm epigenetics and subsequently offspring health and development. Our previous findings in humans showed that urinary anti-androgenic phthalate metabolites in males were associated with altered sperm methylation and blastocyst...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-10-01
|
| Series: | Environment International |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412021003184 |
| _version_ | 1818891324787523584 |
|---|---|
| author | Oladele A. Oluwayiose Chelsea Marcho Haotian Wu Emily Houle Stephen A. Krawetz Alexander Suvorov Jesse Mager J. Richard Pilsner |
| author_facet | Oladele A. Oluwayiose Chelsea Marcho Haotian Wu Emily Houle Stephen A. Krawetz Alexander Suvorov Jesse Mager J. Richard Pilsner |
| author_sort | Oladele A. Oluwayiose |
| collection | DOAJ |
| description | Preconception environmental conditions have been demonstrated to shape sperm epigenetics and subsequently offspring health and development. Our previous findings in humans showed that urinary anti-androgenic phthalate metabolites in males were associated with altered sperm methylation and blastocyst-stage embryo development. To corroborate this, we examined the effect of preconception exposure to di(2-ethylhexyl) phthalate (DEHP) on genome-wide DNA methylation and gene expression profiles in mice. Eight-week old C57BL/6J male mice were exposed to either a vehicle control, low, or high dose of DEHP (2.5 and 25 mg/kg/weight, respectively) for 67 days (~2 spermatogenic cycles) and were subsequently mated with unexposed females. Reduced representation bisulfite sequencing (RRBS) of epididymal sperm was performed and gastrulation stage embryos were collected for RRBS and transcriptome analyses in both embryonic and extra-embryonic lineages. Male preconception DEHP exposure resulted in 704 differentially methylated regions (DMRs; q-value < 0.05; ≥10% methylation change) in sperm, 1,716 DMRs in embryonic, and 3,181 DMRs in extra-embryonic tissue. Of these, 29 DMRs overlapped between sperm and F1 tissues, half of which showed concordant methylation changes between F0 and F1 generations. F1 transcriptomes at E7.5 were also altered by male preconception DEHP exposure including developmental gene families such as Hox, Gata, and Sox. Additionally, gene ontology analyses of DMRs and differentially expressed genes showed enrichment of multiple developmental processes including embryonic development, pattern specification and morphogenesis. These data indicate that spermatogenesis in adult may represent a sensitive window in which exposure to DEHP alters the sperm methylome as well as DNA methylation and gene expression in the developing embryo. |
| first_indexed | 2024-12-19T17:39:00Z |
| format | Article |
| id | doaj.art-d1475a9a8bfd471eae1ef72b990d3320 |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-12-19T17:39:00Z |
| publishDate | 2021-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-d1475a9a8bfd471eae1ef72b990d33202022-12-21T20:12:16ZengElsevierEnvironment International0160-41202021-10-01155106693Paternal preconception phthalate exposure alters sperm methylome and embryonic programmingOladele A. Oluwayiose0Chelsea Marcho1Haotian Wu2Emily Houle3Stephen A. Krawetz4Alexander Suvorov5Jesse Mager6J. Richard Pilsner7Department of Environmental Health Sciences, University of Massachusetts Amherst, Amherst, MA, USADepartment of Environmental Health Sciences, University of Massachusetts Amherst, Amherst, MA, USA; Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, MA, USADepartment of Environmental Health Sciences, Mailman School of Public Health, Columbia University, NY, USADepartment of Environmental Health Sciences, University of Massachusetts Amherst, Amherst, MA, USADepartment of Obstetrics and Gynecology & Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USADepartment of Environmental Health Sciences, University of Massachusetts Amherst, Amherst, MA, USADepartment of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, MA, USADepartment of Environmental Health Sciences, University of Massachusetts Amherst, Amherst, MA, USA; Department of Obstetrics and Gynecology & Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA; Corresponding author at: 275 E. Hancock, Detroit, MI 48201, USA.Preconception environmental conditions have been demonstrated to shape sperm epigenetics and subsequently offspring health and development. Our previous findings in humans showed that urinary anti-androgenic phthalate metabolites in males were associated with altered sperm methylation and blastocyst-stage embryo development. To corroborate this, we examined the effect of preconception exposure to di(2-ethylhexyl) phthalate (DEHP) on genome-wide DNA methylation and gene expression profiles in mice. Eight-week old C57BL/6J male mice were exposed to either a vehicle control, low, or high dose of DEHP (2.5 and 25 mg/kg/weight, respectively) for 67 days (~2 spermatogenic cycles) and were subsequently mated with unexposed females. Reduced representation bisulfite sequencing (RRBS) of epididymal sperm was performed and gastrulation stage embryos were collected for RRBS and transcriptome analyses in both embryonic and extra-embryonic lineages. Male preconception DEHP exposure resulted in 704 differentially methylated regions (DMRs; q-value < 0.05; ≥10% methylation change) in sperm, 1,716 DMRs in embryonic, and 3,181 DMRs in extra-embryonic tissue. Of these, 29 DMRs overlapped between sperm and F1 tissues, half of which showed concordant methylation changes between F0 and F1 generations. F1 transcriptomes at E7.5 were also altered by male preconception DEHP exposure including developmental gene families such as Hox, Gata, and Sox. Additionally, gene ontology analyses of DMRs and differentially expressed genes showed enrichment of multiple developmental processes including embryonic development, pattern specification and morphogenesis. These data indicate that spermatogenesis in adult may represent a sensitive window in which exposure to DEHP alters the sperm methylome as well as DNA methylation and gene expression in the developing embryo.http://www.sciencedirect.com/science/article/pii/S0160412021003184Di(2-ethylhexyl) phthalateDEHPSpermDNA methylationDifferential gene expressionEmbryonic development |
| spellingShingle | Oladele A. Oluwayiose Chelsea Marcho Haotian Wu Emily Houle Stephen A. Krawetz Alexander Suvorov Jesse Mager J. Richard Pilsner Paternal preconception phthalate exposure alters sperm methylome and embryonic programming Environment International Di(2-ethylhexyl) phthalate DEHP Sperm DNA methylation Differential gene expression Embryonic development |
| title | Paternal preconception phthalate exposure alters sperm methylome and embryonic programming |
| title_full | Paternal preconception phthalate exposure alters sperm methylome and embryonic programming |
| title_fullStr | Paternal preconception phthalate exposure alters sperm methylome and embryonic programming |
| title_full_unstemmed | Paternal preconception phthalate exposure alters sperm methylome and embryonic programming |
| title_short | Paternal preconception phthalate exposure alters sperm methylome and embryonic programming |
| title_sort | paternal preconception phthalate exposure alters sperm methylome and embryonic programming |
| topic | Di(2-ethylhexyl) phthalate DEHP Sperm DNA methylation Differential gene expression Embryonic development |
| url | http://www.sciencedirect.com/science/article/pii/S0160412021003184 |
| work_keys_str_mv | AT oladeleaoluwayiose paternalpreconceptionphthalateexposurealtersspermmethylomeandembryonicprogramming AT chelseamarcho paternalpreconceptionphthalateexposurealtersspermmethylomeandembryonicprogramming AT haotianwu paternalpreconceptionphthalateexposurealtersspermmethylomeandembryonicprogramming AT emilyhoule paternalpreconceptionphthalateexposurealtersspermmethylomeandembryonicprogramming AT stephenakrawetz paternalpreconceptionphthalateexposurealtersspermmethylomeandembryonicprogramming AT alexandersuvorov paternalpreconceptionphthalateexposurealtersspermmethylomeandembryonicprogramming AT jessemager paternalpreconceptionphthalateexposurealtersspermmethylomeandembryonicprogramming AT jrichardpilsner paternalpreconceptionphthalateexposurealtersspermmethylomeandembryonicprogramming |