Placental Proteomics Reveals an Elevated Level of Aldo-Keto Reductase 1‑B1, Highlighting Its Potential Role in Spontaneous Preterm Birth

Preterm birth (PTB) refers to the delivery of a baby before the completion of 37 weeks of gestation. It is a significant global health issue with implications for both mothers and neonates. The placenta is a transient organ crucial in the sustenance of pregnancy until parturition; its dysfunction is associated with different adverse pregnancy outcomes, including PTB. We conducted a nested case-control study of 40 placental tissue samples from preterm and term deliveries to study their comparative protein profiles. Label-free quantitation (LFQ) revealed 23 differentially expressed proteins (DEPs). Aldo-keto reductase-B1 (AKR1B1) protein expression profile exhibited a declining trajectory with an increasing period of gestation (POG). Immunoblotting and immunohistochemistry analyses of placental samples also revealed elevated protein levels in extreme preterm samples. AKR1B1 is a functional Prostaglandin F synthase responsible for the synthesis of Prostaglandin-F2α, a prostanoid that is elevated during parturition and involved in cervical ripening, membrane rupture, myometrial contraction, and inflammation. Hence, our finding supports the idea that elevated AKR1B1 levels play a significant role in the pathology of preterm birth by amplifying Prostaglandin-F2α synthesis in the placental milieu and can be further explored as a potential predictor of this condition. Data are available via ProteomeXchange with the identifier PXD043480.