biostudies-literatureUnknownYi MIntramural NIH HHSIdentifying the factors that regulate female reproduction is crucial to understanding how the environment affects female reproductive health. The vitamin D receptor (VDR) and its ligands (primarily 1,25(OH)₂D₃) have a recognized role in calcium homeostasis; however, their broader impact on female reproduction remains underexplored. We demonstrate that the VDR and its ligands are involved in the hormonal induction of uterine decidualization. Mice fed a vitamin D-deficient diet displayed an impaired hormonally induced decidual response. In a human telomerase reverse transcriptase-immortalized human endometrial stromal cell line (T-HESC), VDR decreased during in vitro decidualization. Small interfering RNA (siRNA) knockdown of VDR in T-HESC enhanced in vitro decidualizatbioRxiv : the preprint server for biology2025.11.14.688535https://www.ebi.ac.uk/biostudies/studies/S-EPMC12642428biostudies-literatureImpact of vitamin D deficiency on defective endometrial decidualization and the repressive role of vitamin D receptor (VDR) in the epigenomic network.PMC12642428ZIC ES103371ZIC ES102506ZIA ES103333ZIA ES103311ZIG ES102825ZIC ES102487ZIC ES102545Bell-Hensley AJukic AMZLi SMassri AJYi MWang TMontague Redecke SGDeMayo FJfalseImpact of vitamin D deficiency on defective endometrial decidualization and the repressive role of vitamin D receptor (VDR) in the epigenomic network.Identifying the factors that regulate female reproduction is crucial to understanding how the environment affects female reproductive health. The vitamin D receptor (VDR) and its ligands (primarily 1,25(OH)₂D₃) have a recognized role in calcium homeostasis; however, their broader impact on female reproduction remains underexplored. We demonstrate that the VDR and its ligands are involved in the hormonal induction of uterine decidualization. Mice fed a vitamin D-deficient diet displayed an impaired hormonally induced decidual response. In a human telomerase reverse transcriptase-immortalized human endometrial stromal cell line (T-HESC), VDR decreased during in vitro decidualization. Small interfering RNA (siRNA) knockdown of VDR in T-HESC enhanced in vitro decidualizat2025-01-01T00:00:00Z2025 Nov2026-06-13T03:13:58.168Z2026-06-13T03:08:51.62ZS-EPMC126424284129292010.1101/2025.11.14.688535