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Developmental origins of male subfertility: role of infection, inflammation, and environmental factors

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Abstract

Male gamete development begins with the specification of primordial cells in the epiblast of the early embryo and is not complete until spermatozoa mature in the epididymis of adult males. This protracted developmental process involves extensive alteration of the paternal germline epigenome. Initially, epigenetic reprogramming in fetal germ cells results in removal of most DNA methylation, including parent-specific epigenetic information. The germ cells then establish sex-specific epigenetic information through de novo methylation and undergo spermatogenesis. Chromatin in haploid germ cells is repackaged into protamines during spermiogenesis, providing further widespread epigenetic reorganization. Finally, after fertilization, epigenetic reprogramming in the preimplantation embryo is necessary for regaining totipotency. These events provide substantial windows during which epigenetic errors either may be corrected or may occur in the germline. There is now increasing evidence that environmental factors such as exposure to toxicants, the parents’ and individual’s diet, and even infectious and inflammatory events in the male reproductive tract may influence epigenetic reprogramming. This, together with other damage inflicted on the germline chromatin, may result in negative consequences for fertility and health. Large epidemiological birth cohort studies have yielded insight into possible causative environmental factors. Together with experimental animal studies, a clearer view of environmental impacts on fetal development and their intergenerational and even transgenerational effects on reproductive health has emerged and is reviewed in this article.

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Acknowledgments

The authors acknowledge the financial support of the Deutsche Forschungsgemeinschaft (KFO 181; GRK 1871; SCHA1531/2-1), the State of Hesse Landesoffensive zur Förderung der wissenschaftlichen Exzellenz (LOEWE) on ‘Male infertility due to infection and inflammation’ (MIBIE), National Health and Medical Research Council grants GNT1043939 and GNT1051223, and the Victorian Government’s Operational Infrastructure Support Program, Australia.

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Authors and Affiliations

  1. Department of Urology, Pediatric Urology and Andrology, Section Molecular Andrology, Justus-Liebig University of Giessen, Giessen, Germany

    Undraga Schagdarsurengin & Klaus Steger

  2. Centre for Genetic Diseases, Hudson Institute for Medical Research and Department of Molecular and Translational Science, Monash University, Clayton, VIC, 3168, Australia

    Patrick Western

  3. Institute of Anatomy and Cell Biology, Unit of Reproductive Biology, Justus-Liebig University of Giessen, Aulweg 123, 35385, Giessen, Germany

    Andreas Meinhardt

Authors
  1. Undraga Schagdarsurengin
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  2. Patrick Western
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  3. Klaus Steger
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  4. Andreas Meinhardt
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Corresponding author

Correspondence to Andreas Meinhardt.

Additional information

This article is a contribution to the special issue on Fetomaternal Cross Talk and Its Effect on Pregnancy Maintenance, Maternal and Offspring Health - Guest Editor: Petra Arck

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Schagdarsurengin, U., Western, P., Steger, K. et al. Developmental origins of male subfertility: role of infection, inflammation, and environmental factors. Semin Immunopathol 38, 765–781 (2016). https://doi.org/10.1007/s00281-016-0576-y

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  • DOI: https://doi.org/10.1007/s00281-016-0576-y

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