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Viral infection of the ovaries compromises pregnancy and reveals innate immune mechanisms protecting fertility

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  • Jelena Tomac, University of Rijeka
  • ,
  • Marija Mazor, University of Rijeka
  • ,
  • Berislav Lisnić, University of Rijeka
  • ,
  • Mijo Golemac, University of Rijeka
  • ,
  • Daria Kveštak, University of Rijeka
  • ,
  • Marina Bralić, University of Rijeka
  • ,
  • Lidija Bilić Zulle, University of Rijeka
  • ,
  • Melanie M. Brinkmann, Helmholtz Centre for Infection Research, Technical University of Braunschweig
  • ,
  • Lars Dölken, University of Würzburg, Helmholtz Centre for Infection Research
  • ,
  • Line S. Reinert
  • Soren R. Paludan
  • Astrid Krmpotić, University of Rijeka
  • ,
  • Stipan Jonjić, University of Rijeka
  • ,
  • Vanda Juranić Lisnić, University of Rijeka

Viral infections during pregnancy are a considerable cause of adverse outcomes and birth defects, and the underlying mechanisms are poorly understood. Among those, cytomegalovirus (CMV) infection stands out as the most common intrauterine infection in humans, putatively causing early pregnancy loss. We employed murine CMV as a model to study the consequences of viral infection on pregnancy outcome and fertility maintenance. Even though pregnant mice successfully controlled CMV infection, we observed highly selective, strong infection of corpus luteum (CL) cells in their ovaries. High infection densities indicated complete failure of immune control in CL cells, resulting in progesterone insufficiency and pregnancy loss. An abundance of gap junctions, absence of vasculature, strong type I interferon (IFN) responses, and interaction of innate immune cells fully protected the ovarian follicles from viral infection. Our work provides fundamental insights into the effect of CMV infection on pregnancy loss and mechanisms protecting fertility.

Original languageEnglish
JournalImmunity
Volume54
Issue7
Pages (from-to)1478-1493.e6
Number of pages23
ISSN1074-7613
DOIs
Publication statusPublished - Jul 2021

Bibliographical note

Publisher Copyright:
© 2021 Elsevier Inc.

    Research areas

  • CMV, corpus luteum, cytomegalovirus, fertility, follicles, innate immunity, interferon, macrophages, NK cells, pregnancy loss, virus

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