Abstract
<title>Abstract</title> <p>Background The peripartum period encompasses physiological, endocrine, and immunological adaptations that ensure maternal health and fetal development. Notably, the molecular correlates of these adaptations in healthy women remain limited, particularly at the transcriptomic level. This study aimed to identify systemic transcriptomic differences between late pregnancy and the early postpartum period in a large cohort of healthy women. Methods RNA sequencing was performed on 112 samples from peripheral blood collected at gestational week 38 (gw38; n = 40) and postpartum week 8 (ppw8; n = 72). The transcriptome was compared while adjusting for age and BMI. Additional covariate-adjusted analyses were performed considering cell-type composition, sex of the fetus, and gestational length. Results A total of 293 differentially expressed genes (DEGs) were identified when comparing ppw8 vs. gw38, with the majority being downregulated in the postpartum period. The postpartum phase was marked by the lower expression of genes involved in erythropoiesis and innate, granulocyte-driven immunity, as well as higher levels of adaptive, antibody-mediated defense transcripts. The directionality and functional patterns of DEGs were largely preserved, while accounting for shifts in cellular heterogeneity from pregnancy to postpartum, alongside the emergence of DEGs in cell-intrinsic regulatory pathways. Conclusions Our results reveal systemic transcriptomic differences from late pregnancy to postpartum, particularly a shift from innate to adaptive immune signatures as well as hematopoietic processes, cellular and metabolic pathways. These findings provide reference data for further understanding of peripartum adaptation and establish a molecular baseline for future investigations into perinatal biology and related disorders.</p>