Abstract
Human uterine stromal cell undergoes decidualization for pregnancy establishment and maintenance, which involved extensive proliferation and differentiation. Increasing studies have suggested that recurrent spontaneous abortion (RSA) may result from defective endometrial stromal decidualization. However, the critical molecular mechanisms underlying impaired decidualization during RSA are still elusive. By using our recently published single-cell RNA sequencing (scRNA-seq) atlas, we found that MYC-associated factor X (MAX) was significantly downregulated in the stromal cells derived from decidual tissues of women with RSA, followed by verification with immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR). MAX knockdown significantly impairs human endometrial stromal cells (HESCs) proliferation as determined by MTS assay and Ki67 immunostaining, and decidualization determined by F-actin, and decidualization markers. RNA-seq together with chromatin immunoprecipitation sequencing (ChIP-seq) and cleavage under targets and release using nuclease sequencing (CUT&RUN-seq) analysis were applied to explore the molecular mechanisms of MAX in regulation of decidualization, followed by dual-luciferase reporter assay to verify that MAX targets to (odd-skipped related transcription factor 2) OSR2 directly. Reduced expression of OSR2 was also confirmed in decidual tissues in women with RSA by IHC and qRT-PCR. OSR2 knockdown also significantly impairs HESCs decidualization. OSR2-overexpression could at least partly rescue the downregulated insulin-like growth factor binding protein 1 (IGFBP1) expression level in response to MAX knockdown. Collectively, MAX deficiency observed in RSA stromal cells not only attenuates HESCs proliferation but also impairs HESCs decidualization by downregulating OSR2 expression at transcriptional level directly.
Highlights
Recurrent spontaneous abortion (RSA) is generally defined as two or more pregnancy losses before 24th gestational week, occurs in 1–5% of women during reproductive age, with an increasing incidence year by year (Bender et al 2018; Liu et al 2021; Yu et al 2021)
We found that MYC-associated factor X (MAX), a transcription factor belonging to basic helix-loop-helix leucine zipper family, was significantly downregulated in the stromal cells derived from decidual tissues of women with RSA using our recently published scRNA-seq atlas (Du et al 2021)
We attempted to disclose the potential molecular mechanisms related to RSA in this study, which may result in a novel insight of the pathogenesis of RSA
Summary
Recurrent spontaneous abortion (RSA) is generally defined as two or more pregnancy losses before 24th gestational week, occurs in 1–5% of women during reproductive age, with an increasing incidence year by year (Bender et al 2018; Liu et al 2021; Yu et al 2021). Extended author information available on the last page of the article as fetal growth restriction, was significantly increased in women who had ever experienced RSA (Ali et al 2020; Cozzolino et al 2019). About half of the etiological causes are elusive, called unexplained RSA (Liu et al 2021). Recent studies indicated that unexplained RSA is associated with abnormal expression of certain transcription factors, like signal transducer and activator of transcription 3 (STAT3) and storkhead box 1 (STOX1) in
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
