RT Journal Article
SR Electronic
T1 “Females Are Not Just ‘Protected’ Males”: Sex-Specific Vulnerabilities in Placenta and Brain after Prenatal Immune Disruption
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0358-19.2019
DO 10.1523/ENEURO.0358-19.2019
VO 6
IS 6
A1 Amy E. Braun
A1 Pamela A. Carpentier
A1 Brooke A. Babineau
A1 Aditi R. Narayan
A1 Michelle L. Kielhold
A1 Hyang Mi Moon
A1 Archana Shankar
A1 Jennifer Su
A1 Vidya Saravanapandian
A1 Ursula Haditsch
A1 Theo D. Palmer
YR 2019
UL http://www.eneuro.org/content/6/6/ENEURO.0358-19.2019.abstract
AB Current perceptions of genetic and environmental vulnerabilities in the developing fetus are biased toward male outcomes. An argument is made that males are more vulnerable to gestational complications and neurodevelopmental disorders, the implication being that an understanding of disrupted development in males is sufficient to understand causal mechanisms that are assumed to be similar but attenuated in females. Here we examine this assumption in the context of immune-driven alterations in fetal brain development and related outcomes in female and male mice. Pregnant C57BL/6 mice were treated with low-dose lipopolysaccharide at embryonic day 12.5. Placental pathology, acute fetal brain inflammation and hypoxia, long-term changes in adult cortex cytoarchitecture, altered densities and ratio of excitatory (Satb2+) to inhibitory (parvalbumin+) neuronal subtypes, postnatal growth, and behavior outcomes were compared between male and female offspring. We find that while males experience more pronounced placental pathology, fetal brain hypoxia, depleted PV and Satb2+ densities, and social and learning-related behavioral abnormalities, females exhibit unique acute inflammatory signaling in fetal brain, postnatal growth delay, opposite alterations in cortical PV densities, changes in juvenile behavior, delayed postnatal body growth, and elevated anxiety-related behavior as adults. While males are more severely impacted by prenatal immune disruption by several measures, females exposed to the same insult exhibit a unique set of vulnerabilities and developmental consequences that is not present in males. Our results clearly outline disparate sex-specific features of prenatal vulnerability to inflammatory insults and warn against the casual extrapolation of male disease mechanisms to females.