title: Paternal sepsis induces alterations of the sperm methylome and dampens offspring immune responses—an animal study
creator: Bomans, Katharina
creator: Schenz, Judith
creator: Tamulyte, Sandra
creator: Schaack, Dominik
creator: Weigand, Markus Alexander
creator: Uhle, Florian
subject: ddc-610
subject: 610 Medical sciences Medicine
description: Background: Sepsis represents the utmost severe consequence of infection, involving a dysregulated and self-damaging immune response of the host. While different environmental exposures like chronic stress or malnutrition have been well described to reprogram the germline and subsequently offspring attributes, the intergenerational impact of sepsis as a tremendous immunological stressor has not been examined yet.    Methods: Polymicrobial sepsis in 12-week-old male C57BL/6 mice was induced by cecal ligation and puncture (CLP), followed by a mating of the male survivors (or appropriate sham control animals) 6 weeks later with healthy females. Alveolar macrophages of offspring animals were isolated and stimulated with either LPS or Zymosan, and supernatant levels of TNF-α were quantified by ELISA. Furthermore, systemic cytokine response to intraperitoneally injected LPS was assessed after 24 h. Also, morphology, motility, and global DNA methylation of the sepsis survivors’ sperm was examined.    Results: Comparative reduced reduction bisulfite sequencing (RRBS) of sperm revealed changes of DNA methylation (n = 381), most pronounced in the intergenic genome as well as within introns of developmentally relevant genes. Offspring of sepsis fathers exhibited a slight decrease in body weight, with a more pronounced weight difference in male animals (CLP vs. sham). Male descendants of sepsis fathers, but not female descendants, exhibited lower plasma concentrations of IL-6, TNF-alpha, and IL-10 24 h after injection of LPS. In line, only alveolar macrophages of male descendants of sepsis fathers produced less TNF-alpha upon Zymosan stimulation compared to sham descendants, while LPS responses kept unchanged.    Conclusion: We can prove that male—but surprisingly not female—descendants of post-sepsis fathers show a dampened systemic as well as pulmonary immune response. Based on this observation of an immune hypo-responsivity, we propose that male descendants of sepsis fathers are at risk to develop fungal and bacterial infections and might benefit from therapeutic immune modulation.
publisher: BioMed Central ; Springer
date: 2018
type: Article
type: info:eu-repo/semantics/article
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/24793/1/13148_2018_Article_522.pdf
identifier: DOI:
identifier: urn:nbn:de:bsz:16-heidok-247934
identifier:   Bomans, Katharina ; Schenz, Judith ; Tamulyte, Sandra ; Schaack, Dominik ; Weigand, Markus Alexander ; Uhle, Florian  (2018) Paternal sepsis induces alterations of the sperm methylome and dampens offspring immune responses—an animal study.  Clinical Epigenetics, 10 (89).  pp. 1-10.  ISSN 1868-7075     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/24793/
rights: info:eu-repo/semantics/openAccess
rights: Please see front page of the work (Sorry, Dublin Core plugin does not recognise license id)
language: eng