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Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood

2018; Nature Portfolio; Volume: 3; Issue: 10 Linguagem: Inglês

10.1038/s41564-018-0236-1

2058-5276

Stephanie Stanelle‐Bertram, Kerstin Walendy-Gnirß, Thomas Speiseder, Swantje Thiele, Ivy Asantewaa Asante, Carola Dreier, Nancy Mounogou Kouassi, Annette Preuß, Gundula Pilnitz-Stolze, Ursula Müller, Stefanie Thanisch, Melanie Richter, Robin Scharrenberg, Vanessa Kraus, Ronja Dörk, Lynn Schau, Vanessa Herder, Ingo Gerhauser, Vanessa M. Pfankuche, Christopher Käufer, Inken Waltl, Thaís Moraes, Julie Sellau, Stefan Hoenow, Jonas Schmidt‐Chanasit, Stéphanie Jansen, Benjamin Schattling, Harald Ittrich, Udo Bartsch, Thomas Renné, Ralf Bartenschlager, Petra Arck, Dániel Cadar, Manuel A. Friese, Olli Vapalahti, Hanna Lotter, Sany Benites, Lane Rolling, Martin Gabriel, Wolfgang Baumgärtner, Fabio Morellini, Sabine M. Hölter, Oana V. Amarie, Helmut Fuchs, Martin Hrabé de Angelis, Wolfgang Löscher, Froylán Calderón de Anda, Gülşah Gabriel,

Child Nutrition and Water Access

Congenital Zika virus (ZIKV) syndrome may cause fetal microcephaly in ~1% of affected newborns. Here, we investigate whether the majority of clinically inapparent newborns might suffer from long-term health impairments not readily visible at birth. Infection of immunocompetent pregnant mice with high-dose ZIKV caused severe offspring phenotypes, such as fetal death, as expected. By contrast, low-dose (LD) maternal ZIKV infection resulted in reduced fetal birth weight but no other obvious phenotypes. Male offspring born to LD ZIKV-infected mothers had increased testosterone (TST) levels and were less likely to survive in utero infection compared to their female littermates. Males also presented an increased number of immature neurons in apical and basal hippocampal dendrites, while female offspring had immature neurons in basal dendrites only. Moreover, male offspring with high but not very high (storm) TST levels were more likely to suffer from learning and memory impairments compared to females. Future studies are required to understand the impact of TST on neuropathological and neurocognitive impairments in later life. In summary, increased sex-specific vigilance is required in countries with high ZIKV prevalence, where impaired neurodevelopment may be camouflaged by a healthy appearance at birth. Male offspring of pregnant mice infected with a low dose of Zika virus infection have increased testosterone levels, an increased number of immature neurons in apical hippocampal dendrites and are less likely to survive in utero infection than female littermates.