An IGF1-expressing endometrial stromal cell population is associated with human decidualization

Abstract

Background Decidualization refers to the process of transformation of endometrial stromal fibroblast cells into specialized decidual stromal cells that provide a nutritive and immunoprivileged matrix essential for blastocyst implantation and placental development. Deficiencies in decidualization are associated with a variety of pregnancy disorders, including female infertility, recurrent implantation failure (RIF), and miscarriages. Despite the increasing number of genes reportedly associated with endometrial receptivity and decidualization, the cellular and molecular mechanisms triggering and underlying decidualization remain largely unknown. Here, we analyze single-cell transcriptional profiles of endometrial cells during the window of implantation and decidual cells of early pregnancy, to gains insights on the process of decidualization. Results We observed a unique IGF1+ stromal cell that may initiate decidualization by single-cell RNA sequencing. We found the IL1B+ stromal cells promote gland degeneration and decidua hemostasis. We defined a subset of NK cells for accelerating decidualization and extravillous trophoblast (EVT) invasion by AREG-IGF1 and AREG-CSF1 regulatory axe. Further analysis indicates that EVT promote decidualization possibly by multiply pathways. Additionally, a systematic repository of cell–cell communication for decidualization was developed. An aberrant ratio conversion of IGF1+ stromal cells to IGF1R+ stromal cells is observed in unexplained RIF patients. Conclusions Overall, a unique subpopulation of IGF1+ stromal cell is involved in initiating decidualization. Our observations provide deeper insights into the molecular and cellular characterizations of decidualization, and a platform for further development of evaluation of decidualization degree and treatment for decidualization disorder-related diseases.

Quercetin enhances decidualization through AKT-ERK-p53 signaling and supports a role for senescence in endometriosis

“…IGFBP1 expression by control eSCs following cAMP+MPA-induced decidualization was confirmed by confocal microscopy (Figure 1D). IGFBP1 protein was absent without deciduogenic stimulation, and as previously described 30 not all cells express IGFBP1 following cAMP+MPA stimulation. Furthermore, quercetin increased cAMP+MPA-induced IGFBP1 expression by eSCs as determined by confocal microscopy (Figure 1D).…”

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

“…Our results indicated that Id2 , considered as canonical direct transcriptional targets of BMP-SMAD signaling ( Hollnagel et al, 1999 ; Miyazono and Miyazawa, 2002 ), is also regulated by PR. We also confirmed that known P4-responsive genes such as Tgfbr2 ( Holloran et al, 2020 ) and Runx1 ( Dinh et al, 2023 ), as well as decidual markers such as Foxo1 ( Vasquez et al, 2018 ) and Igf1 ( Shi et al, 2022 ), were co-regulated by SMAD1, SMAD5, and PR ( Figure 5C ).…”

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

“…Our results indicated that Id2 , considered as canonical direct transcriptional targets of BMP-SMAD signaling 72, 73 is also regulated by PR. We also confirmed that known P4-responsive genes such as Tgfbr2 74 and Runx1 75 , as well as decidual markers such as Foxo1 76 and Igf1 77 , were co-regulated by SMAD1, SMAD5 and PR (Figure 5C).…”