The Genomic Architecture of Pregnancy-Associated Plasticity in the Maternal Mouse Hippocampus

Abstract

Pregnancy is associated with extraordinary plasticity in the maternal brain. Studies in humans and other mammals suggest extensive structural and functional remodeling of the female brain during and after pregnancy. However, we understand remarkably little about the molecular underpinnings of this natural phenomenon. To gain insight into pregnancy-associated hippocampal plasticity, we performed single nucleus RNA-seq and single nucleus ATAC-seq from the mouse hippocampus before, during, and after pregnancy. We identified cell-typespecific transcriptional and epigenetic signatures associated with pregnancy and post-partum adaptation. In addition, we analyzed receptor-ligand interactions and transcription factor motifs that inform hippocampal cell type identity and provide evidence of pregnancy-associated adaption. In total, this data provides a unique resource of coupled transcriptional and epigenetic data across a dynamic time period in the mouse hippocampus and suggests opportunities for functional interrogation of hormone-mediated plasticity.

Neuroanatomical changes observed over the course of a human pregnancy

“…These neuromodulatory hormones also drive significant reorganization of the central nervous system. New mechanistic insights from animal models converge on pregnancy as a period of remarkable neuroplasticity (Puri et al, 2023; Celik et al, 2022; Barrière et al, 2021; Haim et al, 2017; Brunton & Russell et al, 2008). In humans, reductions in gray matter volume (GMV) have been observed postpartum (Hoekzema et al, 2017, 2022; Martínez-García, et al, 2021a), particularly in regions central to theory-of-mind processing (Hoekzema et al, 2017).…”

“…These neuromodulatory hormones also drive significant reorganization of the central nervous system. Evidence from animal models and human studies converge on pregnancy as a period of remarkable neuroplasticity (Brunton & Russell et al, 2008; Haim et al, 2017; Barrière et al, 2021; Celik et al, 2022; Puri et al, 2023; Chaker et al, 2023; see Diamond et al, 1971 for one of the earliest known observations). Gestational increases in steroid hormone synthesis drive neurogenesis, dendritic spine growth, microglial proliferation, myelination, and astrocyte remodeling (for review, see Servin-Barthet et al, 2023).…”