Prenatal maternal stress promotes neural stem cell proliferation in the ependymal-subventricular zone of adult male offspring

Perturbations during critical time windows in the normal series of development can lead to adverse functional consequences that manifest later in life. Here, we report that prenatal stress (PNS) during the last week of gestation (E14-delivery) dramatically increased the number of proliferating neural stem/progenitor cells (NSC/NPCs) in the ependymal-subventricular zone (E-SVZ) of male mouse offspring. PNS did not cause significant cell death or a deficit in neuroblast migration to the olfactory bulb (OB). Olfactory behavioral tests showed that while prenatally stressed male mice displayed normal olfactory function in differentiating nonsocial odors, these mice showed impairment in discriminating different social smells. Bulk and single nucleus transcriptomic analyses combined with rescue assays using mitogen-activated protein kinases (MAPK) phosphorylation inhibitors revealed that PNS exposure during the critical period of neurogenesis promoted NSC/NPC proliferation in adult male offspring by sustaining MAPK3/1 activity. Compared to prenatally stressed males, their female littermates showed less change in the number of proliferating cells in the E-SVZ. ### Competing Interest Statement The authors have declared no competing interest.