Deciphering the role of PGRMC1 during human decidualization using an in vitro approach.

Abstract

CONTEXT\nNon-classical membrane progesterone receptor (mPRs) and PGRMC1 expression have been detected in endometrium, but their role in decidualization was not yet investigated. We previously demonstrated PGRMC1 downregulation in receptive endometrium and that its overexpression inhibits decidualization. Furthermore, during decidualization, PGRMC1 mainly interacts with proteins involved in biosynthesis, intracellular transport and mitochondrial activity.\n\n\nOBJECTIVE\nTo determine PGRMC1 and mPRs signaling role during decidualization.\n\n\nDESIGN AND INTERVENTIONS\nIsolated primary endometrial stromal cells (EnSC) were in vitro decidualized in presence of classic stimuli (E2+P4), PGRMC1 inhibitor (AG205), or membrane-impermeable P4 (P4-BSA).\n\n\nSETTING AND PARTICIPANTS\nEndometrial biopsies from 19 fertile oocyte donors attending IVI-Valencia IVF clinic.\n\n\nMAIN OUTCOME MEASURE(S)\nEnSC decidualization was evaluated by prolactin ELISA and F-actin immunostaining. Progesterone receptor localization was evaluated by immunofluorescence. EnSC transcriptomic profiles were analyzed by microarray technology.\n\n\nRESULT(S)\nPGRMC1 inhibition during EnSC decidualization (AG205dEnSC) does not interfere with EnSC cytoskeletal rearrangements and prolactin secretion. However, global transcriptional profiling revealed more differentially expressed genes in AG205dEnSC than in dEnSC, compared with non-decidualized EnSC (ndEnSC). In silico analysis showed that PGRMC1 inhibition upregulated more genes related to metabolism, molecular transport, and hormonal biosynthesis compared to control dEnSC. EnSC decidualized in the presence of P4-BSA showed a similar behavior as ndEnSC in terms of morphological features, absence of prolactin secretion, and transcriptomic pattern.\n\n\nCONCLUSION(S)\nOur findings associate PGRMC1 to hormonal biosynthesis, metabolism, and vesicular transport-important cellular functions for dEnSC supporting pregnancy. Activation of membrane P4 receptor signaling alone was unable to induce downstream effects needed for proper decidualization.