Register      Login
Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Environmental impacts on sperm and oocyte epigenetics affect embryo cell epigenetics and transcription to promote the epigenetic inheritance of pathology and phenotypic variation

Eric Nilsson A , Millissia Ben Maamar A and Michael K. Skinner A B
+ Author Affiliations
- Author Affiliations

A Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164-4236, USA.

B Corresponding author. Email: skinner@wsu.edu

Reproduction, Fertility and Development 33(2) 102-107 https://doi.org/10.1071/RD20255
Published: 8 January 2021

Abstract

Previous studies have demonstrated that exposure to environmental factors can cause epigenetic modifications to germ cells, particularly sperm, to promote epigenetic and transcriptome changes in the embryo. These germ cell and embryo cell epigenetic alterations are associated with phenotypic changes in offspring. Epigenetic inheritance requires epigenetic changes (i.e. epimutations) in germ cells that promote epigenetic and gene expression changes in embryos. The objective of this perspective is to examine the evidence that germ cell epigenome modifications are associated with embryo cell epigenetic and transcriptome changes that affect the subsequent development of all developing somatic cells to promote phenotype change. Various epigenetic changes in sperm, including changes to histone methylation, histone retention, non-coding RNA expression and DNA methylation, have been associated with alterations in embryo cell epigenetics and gene expression. Few studies have investigated this link for oocytes. The studies reviewed herein support the idea that environmentally induced epigenetic changes in germ cells affect alterations in embryo cell epigenetics and transcriptomes that have an important role in the epigenetic inheritance of pathology and phenotypic change.

Keywords: DNA methylation, embryonic cells, epigenetics, histone modifications, inheritance, non-coding RNA, oocyte, sperm, stem cells, transgenerational.


References

Anway, M. D., Cupp, A. S., Uzumcu, M., and Skinner, M. K. (2005). Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 308, 1466–1469.
Epigenetic transgenerational actions of endocrine disruptors and male fertility.Crossref | GoogleScholarGoogle Scholar | 15933200PubMed |

Aurich, C., Schreiner, B., Ille, N., Alvarenga, M., and Scarlet, D. (2016). Cytosine methylation of sperm DNA in horse semen after cryopreservation. Theriogenology 86, 1347–1352.
Cytosine methylation of sperm DNA in horse semen after cryopreservation.Crossref | GoogleScholarGoogle Scholar | 27242182PubMed |

Ben Maamar, M., Sadler-Riggleman, I., Beck, D., McBirney, M., Nilsson, E., Klukovich, R., Xie, Y., Tang, C., Yan, W., and Skinner, M. K. (2018a). Alterations in sperm DNA methylation, non-coding RNA expression, and histone retention mediate vinclozolin-induced epigenetic transgenerational inheritance of disease. Environ. Epigenet. 4, dvy010.
Alterations in sperm DNA methylation, non-coding RNA expression, and histone retention mediate vinclozolin-induced epigenetic transgenerational inheritance of disease.Crossref | GoogleScholarGoogle Scholar | 29732173PubMed |

Ben Maamar, M., Sadler-Riggleman, I., Beck, D., and Skinner, M. K. (2018b). Epigenetic transgenerational inheritance of altered sperm histone retention sites. Sci. Rep. 8, 5308.
Epigenetic transgenerational inheritance of altered sperm histone retention sites.Crossref | GoogleScholarGoogle Scholar | 29593303PubMed |

Ben Maamar, M., Beck, D., Nilsson, E., McCarrey, J. R., and Skinner, M. K. (2020). Developmental origins of transgenerational sperm histone retention following ancestral exposures. Dev. Biol. 465, 31–45.
Developmental origins of transgenerational sperm histone retention following ancestral exposures.Crossref | GoogleScholarGoogle Scholar | 32628935PubMed |

Carrell, D. T., and Hammoud, S. S. (2010). The human sperm epigenome and its potential role in embryonic development. Mol. Hum. Reprod. 16, 37–47.
The human sperm epigenome and its potential role in embryonic development.Crossref | GoogleScholarGoogle Scholar | 19906823PubMed |

Chaffin, C. L., Latham, K. E., Mtango, N. R., Midic, U., and VandeVoort, C. A. (2014). Dietary sugar in healthy female primates perturbs oocyte maturation and in vitro preimplantation embryo development. Endocrinology 155, 2688–2695.
Dietary sugar in healthy female primates perturbs oocyte maturation and in vitro preimplantation embryo development.Crossref | GoogleScholarGoogle Scholar | 24731100PubMed |

Chen, Q., Yan, M., Cao, Z., Li, X., Zhang, Y., Shi, J., Feng, G. H., Peng, H., Zhang, X., Zhang, Y., Qian, J., Duan, E., Zhai, Q., and Zhou, Q. (2016). Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science 351, 397–400.
Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder.Crossref | GoogleScholarGoogle Scholar | 26721680PubMed |

Di Emidio, G., D’Aurora, M., Placidi, M., Franchi, S., Rossi, G., Stuppia, L., Artini, P. G., Tatone, C., and Gatta, V. (2019). Pre-conceptional maternal exposure to cyclophosphamide results in modifications of DNA methylation in F1 and F2 mouse oocytes: evidence for transgenerational effects. Epigenetics 14, 1057–1064.
Pre-conceptional maternal exposure to cyclophosphamide results in modifications of DNA methylation in F1 and F2 mouse oocytes: evidence for transgenerational effects.Crossref | GoogleScholarGoogle Scholar | 31189412PubMed |

Donkin, I., and Barres, R. (2018). Sperm epigenetics and influence of environmental factors. Mol. Metab. 14, 1–11.
Sperm epigenetics and influence of environmental factors.Crossref | GoogleScholarGoogle Scholar | 29525406PubMed |

Fullston, T., Ohlsson Teague, E. M., Palmer, N. O., DeBlasio, M. J., Mitchell, M., Corbett, M., Print, C. G., Owens, J. A., and Lane, M. (2013). Paternal obesity initiates metabolic disturbances in two generations of mice with incomplete penetrance to the F2 generation and alters the transcriptional profile of testis and sperm microRNA content. FASEB J. 27, 4226–4243.
Paternal obesity initiates metabolic disturbances in two generations of mice with incomplete penetrance to the F2 generation and alters the transcriptional profile of testis and sperm microRNA content.Crossref | GoogleScholarGoogle Scholar | 23845863PubMed |

Grandjean, V., Fourre, S., De Abreu, D. A., Derieppe, M. A., Remy, J. J., and Rassoulzadegan, M. (2016). RNA-mediated paternal heredity of diet-induced obesity and metabolic disorders. Sci. Rep. 5, 18193.
RNA-mediated paternal heredity of diet-induced obesity and metabolic disorders.Crossref | GoogleScholarGoogle Scholar |

Ihara, M., Meyer-Ficca, M. L., Leu, N. A., Rao, S., Li, F., Gregory, B. D., Zalenskaya, I. A., Schultz, R. M., and Meyer, R. G. (2014). Paternal poly (ADP-ribose) metabolism modulates retention of inheritable sperm histones and early embryonic gene expression. PLoS Genet. 10, e1004317.
Paternal poly (ADP-ribose) metabolism modulates retention of inheritable sperm histones and early embryonic gene expression.Crossref | GoogleScholarGoogle Scholar | 24810616PubMed |

Jirtle, R. L., and Skinner, M. K. (2007). Environmental epigenomics and disease susceptibility. Nat. Rev. Genet. 8, 253–262.
Environmental epigenomics and disease susceptibility.Crossref | GoogleScholarGoogle Scholar | 17363974PubMed |

Kaneshiro, K. R., Rechtsteiner, A., and Strome, S. (2019). Sperm-inherited H3K27me3 impacts offspring transcription and development in C. elegans. Nat. Commun. 10, 1271.
Sperm-inherited H3K27me3 impacts offspring transcription and development in C. elegans.Crossref | GoogleScholarGoogle Scholar | 30894520PubMed |

Ly, L., Chan, D., Aarabi, M., Landry, M., Behan, N. A., MacFarlane, A. J., and Trasler, J. (2017). Intergenerational impact of paternal lifetime exposures to both folic acid deficiency and supplementation on reproductive outcomes and imprinted gene methylation. Mol. Hum. Reprod. 23, 461–477.
Intergenerational impact of paternal lifetime exposures to both folic acid deficiency and supplementation on reproductive outcomes and imprinted gene methylation.Crossref | GoogleScholarGoogle Scholar | 28535307PubMed |

McCarrey, J. R. (2014). Distinctions between transgenerational and non-transgenerational epimutations. Mol. Cell. Endocrinol. 398, 13–23.
Distinctions between transgenerational and non-transgenerational epimutations.Crossref | GoogleScholarGoogle Scholar | 25079508PubMed |

Nilsson, E., King, S. E., McBirney, M., Kubsad, D., Pappalardo, M., Beck, D., Sadler-Riggleman, I., and Skinner, M. K. (2018a). Vinclozolin induced epigenetic transgenerational inheritance of pathologies and sperm epimutation biomarkers for specific diseases. PLoS One 13, e0202662.
Vinclozolin induced epigenetic transgenerational inheritance of pathologies and sperm epimutation biomarkers for specific diseases.Crossref | GoogleScholarGoogle Scholar | 30157260PubMed |

Nilsson, E. E., Sadler-Riggleman, I., and Skinner, M. K. (2018b). Environmentally induced epigenetic transgenerational inheritance of disease. Environ. Epigenet. 4, dvy016.
Environmentally induced epigenetic transgenerational inheritance of disease.Crossref | GoogleScholarGoogle Scholar | 30038800PubMed |

Oikawa, M., Simeone, A., Hormanseder, E., Teperek, M., Gaggioli, V., O’Doherty, A., Falk, E., Sporniak, M., D’Santos, C., Franklin, V. N. R., Kishore, K., Bradshaw, C. R., Keane, D., Freour, T., David, L., Grzybowski, A. T., Ruthenburg, A. J., Gurdon, J., and Jullien, J. (2020). Epigenetic homogeneity in histone methylation underlies sperm programming for embryonic transcription. Nat. Commun. 11, 3491.
Epigenetic homogeneity in histone methylation underlies sperm programming for embryonic transcription.Crossref | GoogleScholarGoogle Scholar | 32661239PubMed |

Ortiz-Rodriguez, J. M., Ortega-Ferrusola, C., Gil, M. C., Martin-Cano, F. E., Gaitskell-Phillips, G., Rodriguez-Martinez, H., Hinrichs, K., Alvarez-Barrientos, A., Roman, A., and Pena, F. J. (2019). Transcriptome analysis reveals that fertilization with cryopreserved sperm downregulates genes relevant for early embryo development in the horse. PLoS One 14, e0213420.
Transcriptome analysis reveals that fertilization with cryopreserved sperm downregulates genes relevant for early embryo development in the horse.Crossref | GoogleScholarGoogle Scholar | 31276504PubMed |

Perez, M. F., and Lehner, B. (2019). Intergenerational and transgenerational epigenetic inheritance in animals. Nat. Cell Biol. 21, 143–151.
Intergenerational and transgenerational epigenetic inheritance in animals.Crossref | GoogleScholarGoogle Scholar | 30602724PubMed |

Radford, E. J., Ito, M., Shi, H., Corish, J. A., Yamazawa, K., Isganaitis, E., Seisenberger, S., Hore, T. A., Reik, W., Erkek, S., Peters, A., Patti, M. E., and Ferguson-Smith, A. C. (2014). In utero effects. In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism. Science 345, 1255903.
In utero effects. In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism.Crossref | GoogleScholarGoogle Scholar | 25011554PubMed |

Reik, W., and Surani, M. A. (2015). Germline and pluripotent stem cells. Cold Spring Harb. Perspect. Biol. 7, a019422.
Germline and pluripotent stem cells.Crossref | GoogleScholarGoogle Scholar | 26525151PubMed |

Roemer, I., Reik, W., Dean, W., and Klose, J. (1997). Epigenetic inheritance in the mouse. Curr. Biol. 7, 277–280.
Epigenetic inheritance in the mouse.Crossref | GoogleScholarGoogle Scholar | 9094308PubMed |

Ross, P. J., and Canovas, S. (2016). Mechanisms of epigenetic remodelling during preimplantation development. Reprod. Fertil. Dev. 28, 25–40.
Mechanisms of epigenetic remodelling during preimplantation development.Crossref | GoogleScholarGoogle Scholar | 27062872PubMed |

Saab, B. J., and Mansuy, I. M. (2014). Neurobiological disease etiology and inheritance: an epigenetic perspective. J. Exp. Biol. 217, 94–101.
Neurobiological disease etiology and inheritance: an epigenetic perspective.Crossref | GoogleScholarGoogle Scholar | 24353208PubMed |

Saenz-de-Juano, M. D., Ivanova, E., Billooye, K., Herta, A. C., Smitz, J., Kelsey, G., and Anckaert, E. (2019). Genome-wide assessment of DNA methylation in mouse oocytes reveals effects associated with in vitro growth, superovulation, and sexual maturity. Clin. Epigenetics 11, 197.
Genome-wide assessment of DNA methylation in mouse oocytes reveals effects associated with in vitro growth, superovulation, and sexual maturity.Crossref | GoogleScholarGoogle Scholar | 31856890PubMed |

Seisenberger, S., Peat, J. R., and Reik, W. (2013). Conceptual links between DNA methylation reprogramming in the early embryo and primordial germ cells. Curr. Opin. Cell Biol. 25, 281–288.
Conceptual links between DNA methylation reprogramming in the early embryo and primordial germ cells.Crossref | GoogleScholarGoogle Scholar | 23510682PubMed |

Shnorhavorian, M., Schwartz, S. M., Stansfeld, B., Sadler-Riggleman, I., Beck, D., and Skinner, M. K. (2017). Differential DNA methylation regions in adult human sperm following adolescent chemotherapy: potential for epigenetic inheritance. PLoS One 12, e0170085.
Differential DNA methylation regions in adult human sperm following adolescent chemotherapy: potential for epigenetic inheritance.Crossref | GoogleScholarGoogle Scholar | 28146567PubMed |

Siddeek, B., Mauduit, C., Simeoni, U., and Benahmed, M. (2018). Sperm epigenome as a marker of environmental exposure and lifestyle, at the origin of diseases inheritance. Mutat. Res. 778, 38–44.
Sperm epigenome as a marker of environmental exposure and lifestyle, at the origin of diseases inheritance.Crossref | GoogleScholarGoogle Scholar | 30454681PubMed |

Skinner, M. K. (2008). What is an epigenetic transgenerational phenotype? F3 or F2. Reprod. Toxicol. 25, 2–6.
What is an epigenetic transgenerational phenotype? F3 or F2.Crossref | GoogleScholarGoogle Scholar | 17949945PubMed |

Stringer, J. M., Forster, S. C., Qu, Z., Prokopuk, L., O’Bryan, M. K., Gardner, D. K., White, S. J., Adelson, D., and Western, P. S. (2018). Reduced PRC2 function alters male germline epigenetic programming and paternal inheritance. BMC Biol. 16, 104.
Reduced PRC2 function alters male germline epigenetic programming and paternal inheritance.Crossref | GoogleScholarGoogle Scholar | 30236109PubMed |

Tang, W. W., Kobayashi, T., Irie, N., Dietmann, S., and Surani, M. A. (2016). Specification and epigenetic programming of the human germ line. Nat. Rev. Genet. 17, 585–600.
Specification and epigenetic programming of the human germ line.Crossref | GoogleScholarGoogle Scholar | 27573372PubMed |

Teltumbade, M., Bhalla, A., and Sharma, A. (2020). Paternal inheritance of diet induced metabolic traits correlates with germline regulation of diet induced coding gene expression. Genomics 112, 567–573.
Paternal inheritance of diet induced metabolic traits correlates with germline regulation of diet induced coding gene expression.Crossref | GoogleScholarGoogle Scholar | 30986426PubMed |

Teperek, M., Simeone, A., Gaggioli, V., Miyamoto, K., Allen, G. E., Erkek, S., Kwon, T., Marcotte, E. M., Zegerman, P., Bradshaw, C. R., Peters, A. H., Gurdon, J. B., and Jullien, J. (2016). Sperm is epigenetically programmed to regulate gene transcription in embryos. Genome Res. 26, 1034–1046.
Sperm is epigenetically programmed to regulate gene transcription in embryos.Crossref | GoogleScholarGoogle Scholar | 27034506PubMed |

Toschi, P., Capra, E., Anzalone, D. A., Lazzari, B., Turri, F., Pizzi, F., Scapolo, P. A., Stella, A., Williams, J. L., Ajmone Marsan, P., and Loi, P. (2020). Maternal peri-conceptional undernourishment perturbs offspring sperm methylome. Reproduction 159, 513–523.
Maternal peri-conceptional undernourishment perturbs offspring sperm methylome.Crossref | GoogleScholarGoogle Scholar | 32103819PubMed |

Van Cauwenbergh, O., Di Serafino, A., Tytgat, J., and Soubry, A. (2020). Transgenerational epigenetic effects from male exposure to endocrine-disrupting compounds: a systematic review on research in mammals. Clin. Epigenetics 12, 65.
Transgenerational epigenetic effects from male exposure to endocrine-disrupting compounds: a systematic review on research in mammals.Crossref | GoogleScholarGoogle Scholar | 32398147PubMed |

Wang, Y., Liu, H., and Sun, Z. (2017). Lamarck rises from his grave: parental environment-induced epigenetic inheritance in model organisms and humans. Biol. Rev. Camb. Philos. Soc. 92, 2084–2111.
Lamarck rises from his grave: parental environment-induced epigenetic inheritance in model organisms and humans.Crossref | GoogleScholarGoogle Scholar | 28220606PubMed |

Xavier, M. J., Roman, S. D., Aitken, R. J., and Nixon, B. (2019). Transgenerational inheritance: how impacts to the epigenetic and genetic information of parents affect offspring health. Hum. Reprod. Update 25, 519–541.
Transgenerational inheritance: how impacts to the epigenetic and genetic information of parents affect offspring health.Crossref | GoogleScholarGoogle Scholar |

Yan, W. (2014). Potential roles of noncoding RNAs in environmental epigenetic transgenerational inheritance. Mol. Cell. Endocrinol. 398, 24–30.
Potential roles of noncoding RNAs in environmental epigenetic transgenerational inheritance.Crossref | GoogleScholarGoogle Scholar | 25224488PubMed |

Yuan, S., Schuster, A., Tang, C., Yu, T., Ortogero, N., Bao, J., Zheng, H., and Yan, W. (2016). Sperm-borne miRNAs and endo-siRNAs are important for fertilization and preimplantation embryonic development. Development 143, 635–647.
Sperm-borne miRNAs and endo-siRNAs are important for fertilization and preimplantation embryonic development.Crossref | GoogleScholarGoogle Scholar | 26718009PubMed |

Zeng, C., Peng, W., Ding, L., He, L., Zhang, Y., Fang, D., and Tang, K. (2014). A preliminary study on epigenetic changes during boar sperm cryopreservation. Cryobiology 69, 119–127.
A preliminary study on epigenetic changes during boar sperm cryopreservation.Crossref | GoogleScholarGoogle Scholar | 24974820PubMed |