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The author argues that SMAD1 and SMAD5 play crucial roles in mediating BMP signaling pathways and the transcriptional response to progesterone during early pregnancy through genomic binding signatures. The approach involves generating novel mouse lines with affinity tags to study the intersection of these pathways.


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Endometrial decidualization, a prerequisite for successful pregnancies, relies on transcriptional reprogramming driven by progesterone receptor (PR) and bone morphogenetic protein (BMP)-SMAD1/SMAD5 signaling pathways. Despite their critical roles in early pregnancy, how these pathways intersect in reprogramming the endometrium into a receptive state remains unclear. To define how SMAD1 and/or SMAD5 integrate BMP signaling in the uterus during early pregnancy, we generated two novel transgenic mouse lines with affinity tags inserted into the endogenous SMAD1 and SMAD5 loci ( Smad1HA/HA and Smad5PA/PA) . By profiling the genome-wide distribution of SMAD1, SMAD5, and PR in the mouse uterus, we demonstrated the unique and shared roles of SMAD1 and SMAD5 during the window of implantation. We also showed the presence of a conserved SMAD1, SMAD5, and PR genomic binding signature in the uterus during early pregnancy. To functionally characterize the translational aspects of our findings, we demonstrated that SMAD1/5 knockdown in human endometrial stromal cells suppressed expressions of canonical decidual markers ( IGFBP1, PRL, FOXO1) and PR-responsive genes ( RORB , KLF15) . Here, our studies provide novel tools to study BMP signaling pathways and highlight the fundamental roles of SMAD1/5 in mediating both BMP signaling pathways and the transcriptional response to progesterone (P4) during early pregnancy.

### Competing Interest Statement

The authors have declared no competing interest.

Affinity-tagged SMAD1 and SMAD5 mouse lines reveal transcriptional reprogramming mechanisms during early pregnancy

transcriptional-reprogramming-in-early-pregnancy-revealed-by-smad1-and-smad5-mouse-lines


Transcriptional Reprogramming in Early Pregnancy Revealed by SMAD1 and SMAD5 Mouse Lines


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Transcriptional Reprogramming in Early Pregnancy