Frontiers in Immunology (Feb 2020)
Prenatal Maternal Stress Causes Preterm Birth and Affects Neonatal Adaptive Immunity in Mice
- Valeria Garcia-Flores,
- Valeria Garcia-Flores,
- Roberto Romero,
- Roberto Romero,
- Roberto Romero,
- Roberto Romero,
- Roberto Romero,
- Roberto Romero,
- Amy-Eunice Furcron,
- Amy-Eunice Furcron,
- Dustyn Levenson,
- Dustyn Levenson,
- Jose Galaz,
- Jose Galaz,
- Chengrui Zou,
- Chengrui Zou,
- Sonia S. Hassan,
- Sonia S. Hassan,
- Sonia S. Hassan,
- Sonia S. Hassan,
- Chaur-Dong Hsu,
- Chaur-Dong Hsu,
- Chaur-Dong Hsu,
- David Olson,
- Gerlinde A. S. Metz,
- Nardhy Gomez-Lopez,
- Nardhy Gomez-Lopez,
- Nardhy Gomez-Lopez
Affiliations
- Valeria Garcia-Flores
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Detroit, MI, United States
- Valeria Garcia-Flores
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States
- Roberto Romero
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Detroit, MI, United States
- Roberto Romero
- Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, United States
- Roberto Romero
- Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, United States
- Roberto Romero
- Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, United States
- Roberto Romero
- Detroit Medical Center, Detroit, MI, United States
- Roberto Romero
- Department of Obstetrics and Gynecology, Florida International University, Miami, FL, United States
- Amy-Eunice Furcron
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Detroit, MI, United States
- Amy-Eunice Furcron
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States
- Dustyn Levenson
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Detroit, MI, United States
- Dustyn Levenson
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States
- Jose Galaz
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Detroit, MI, United States
- Jose Galaz
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States
- Chengrui Zou
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Detroit, MI, United States
- Chengrui Zou
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States
- Sonia S. Hassan
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Detroit, MI, United States
- Sonia S. Hassan
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States
- Sonia S. Hassan
- Office of Women's Health, Integrative Biosciences Center, Wayne State University, Detroit, MI, United States
- Sonia S. Hassan
- Department of Physiology, Wayne State University School of Medicine, Detroit, MI, United States
- Chaur-Dong Hsu
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Detroit, MI, United States
- Chaur-Dong Hsu
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States
- Chaur-Dong Hsu
- Department of Physiology, Wayne State University School of Medicine, Detroit, MI, United States
- David Olson
- 0Department of Obstetrics and Gynecology, Pediatrics, and Physiology, University of Alberta, Edmonton, AB, Canada
- Gerlinde A. S. Metz
- 1Department of Neuroscience, Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, AB, Canada
- Nardhy Gomez-Lopez
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Detroit, MI, United States
- Nardhy Gomez-Lopez
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States
- Nardhy Gomez-Lopez
- 2Department of Immunology, Microbiology and Biochemistry, Wayne State University School of Medicine, Detroit, MI, United States
- DOI
- https://doi.org/10.3389/fimmu.2020.00254
- Journal volume & issue
-
Vol. 11
Abstract
Maternal stress is a well-established risk factor for preterm birth and has been associated with adverse neonatal outcomes in the first and subsequent generations, including increased susceptibility to disease and lasting immunological changes. However, a causal link between prenatal maternal stress and preterm birth, as well as compromised neonatal immunity, has yet to be established. To fill this gap in knowledge, we used a murine model of prenatal maternal stress across three generations and high-dimensional flow cytometry to evaluate neonatal adaptive immunity. We report that recurrent prenatal maternal stress induced preterm birth in the first and second filial generations and negatively impacted early neonatal growth. Strikingly, prenatal maternal stress induced a systematic reduction in T cells and B cells, the former including regulatory CD4+ T cells as well as IL-4- and IL-17A-producing T cells, in the second generation. Yet, neonatal adaptive immunity gained resilience against prenatal maternal stress by the third generation. We also show that the rate of prenatal maternal stress-induced preterm birth can be reduced upon cessation of stress, though neonatal growth impairments persisted. These findings provide evidence that prenatal maternal stress causes preterm birth and affects neonatal immunity across generations, adverse effects that can be ameliorated upon cessation.
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