Arginine methyltransferase PRMT1 equipoises trophoblast development to prevent early pregnancy loss.

Dasgupta P, Kumar R, Ray S, Roy N, Niloy AJ, Vallakati M, Marsh C, Arnold SJ, Paul S
Nature communications · 2026 · doi:10.1038/s41467-026-75452-4 · PMID:42431891 · PMC13484479
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Abstract

Idiopathic recurrent pregnancy loss (RPL) affects 1-2% of human pregnancies, yet the underlying molecular causes are poorly understood. Here we identify defective Protein Arginine Methyltransferase 1 (PRMT1) function in trophoblast progenitors as a cause of early pregnancy failure. PRMT1 is highly conserved in mammalian trophoblast progenitors, and conditional deletion of Prmt1 in mouse trophoblast progenitors arrests placental and embryonic development, resulting in lethality at ~E7.5. In humans, a subset of idiopathic RPL cases exhibits loss of PRMT1 in cytotrophoblast progenitors (CTBs). Human trophoblast stem cells (hTSCs) derived from these RPL placentas, together with PRMT1-depleted hTSCs, demonstrate an essential role for PRMT1 in maintaining trophoblast progenitor self-renewal. RNA-seq and CUT&RUN analyses reveal that PRMT1 promotes expression of stem-state regulators, including TEAD4 and MYBL2, through enrichment of histone H4 arginine 3 asymmetric dimethylation (H4R3Me2a) at their chromatin loci. PRMT1 is required for extravillous trophoblast (EVT) development, whereas its loss promotes spontaneous syncytiotrophoblast (STB) differentiation. Together, these findings identify the PRMT1-H4R3Me2a axis as a conserved epigenetic regulator of trophoblast development and pregnancy maintenance.

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organisms 90
transgenic mice humans human human mus sp. human human human human rodents human transgenic mice human transgenic mice human human transgenic mice rodents rodents multicellular animals transgenic mice transgenic mice mus sp. mus sp. mus sp. mus sp. mus sp. multicellular animals mus sp. transgenic mice mus sp. transgenic mice pleuropneumonia human human human immunodeficiency virus siv/hiv transgenic mice transgenic mice strain sara e. branham m1027 transgenic mice human human human human transgenic mice transgenic mice transgenic mice zitter rats transgenic mice zitter rats transgenic mice zitter rats humans human human human transgenic mice mus sp. transgenic mice +30 more
chemicals 43
histone arginine dimethylarginine histone arginine neomycin tamoxifen heparin progesterone formaldehyde nitrogen puromycin puromycin puromycin puromycin glutamine r-nostrenol prostaglandin e2 formaldehyde triton triton diethylcarbamazine citrate haematoxylin pyropheophorbide a digitonin phenol chloroform ethanol trypan blue chromium trypan blue puromycin tamoxifen 4-hydroxymethylsteroid mannoprotein histone arginine histone histone arginine arginine histone arginine

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