Loss of Parkinson’s Disease Protein 7 upregulates cytoskeletal protein Palladin and is associated with pregnancy loss

Decidualization is a morphological and biochemical reprograming process in preparation for pregnancy. An impaired decidual response can lead to complications like recurrent pregnancy loss (RPL). Parkinson’s disease protein 7 (PARK7), which encodes the protein DJ-1, is renowned for its pivotal role in Parkinson's disease. It manifests a spectrum of physiological functions that hold potential implications for decidualization-related processes. In this study, we elucidate whether DJ-1 can regulate endometrial function. Our findings demonstrate that DJ-1 is expressed in the endometrium of both humans and mice, with increased levels during the time-dependent decidual transformation of human endometrial stromal cells (EnSC) coinciding with the window of implantation. Analysis of human and mice showed that loss of DJ-1 is associated with RPL. Furthermore, knockdown of DJ-1 in decidualized EnSC lead to a reduced in cell proliferation, increase of reactive oxygen species and upregulation of Palladin expression, as quantified through LC/MS. These alterations subsequently contributed to heightened polymerization, augmented cell migration, and increased cellular stiffness. Importantly, these effects were reversed upon DJ-1 overexpression. These findings collectively propose DJ-1 as a crucial regulator of cytoskeleton dynamics and decidual homeostasis, essential for early pregnancy and preventing the onset of RPL.