Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 30;39(12):e70752.
doi: 10.1096/fj.202500781R.

NR5A1 Deficiency Leads to Decidualization Dysregulation of Stromal Cells and Recurrent Spontaneous Abortion During Early Pregnancy

Jingcong Dai  1 , Huanhuan Jiang  2 , Dan Liu  2 , Zhiyong Dong  2 , Lina Hu  3   4   5 , Fan He  3   4   5 , Tinghe Yu  1
Affiliations

NR5A1 Deficiency Leads to Decidualization Dysregulation of Stromal Cells and Recurrent Spontaneous Abortion During Early Pregnancy

Jingcong Dai et al. FASEB J. .

Abstract

The differentiation of endometrial stromal cells (ESCs) into decidual stromal cells (DSCs), that is, endometrial decidualization, orchestrates the receptive environment for early embryo development, and defects in decidualization lead to unexplained recurrent spontaneous abortion (URSA). Nuclear receptor subfamily 5 group A member 1 (NR5A1) is involved in endometrial decidualization during early pregnancy, but its role is limitedly understood. Here, we elucidated the association between low expression of NR5A1 and decidualization dysregulation and URSA during early pregnancy, and then elucidated mechanisms of NR5A1 regulating decidualization. In the endometrium, the expression level of NR5A1 in secretory-phase ESCs of URSA patients was lower than that of controls. During early pregnancy, the expression level of NR5A1 in DSCs from URSA patients, and that in decidua of recurrent spontaneous abortion (RSA) mice, were decreased in comparison with controls, respectively. NR5A1 knockdown impaired in vitro decidualization of ESCs by inhibiting the IGFBP1 up-regulation and F-actin formation. In DSCs of early pregnancy mice, NR5A1 was maintained at a higher level from pregnant Day 4. Downknocking NR5A1 by intrauterine injection of RNAi-Nr5a1 lentiviruses in mice increased the embryonic resorption and impaired decidualization by down-regulating the expression of Dtprp and IGFBP1. Dual-luciferase reporter and ChIP-qPCR assays revealed that NR5A1 bound to the IGFBP1 promoter and then activated its transcription. In mice with downknocked NR5A1 in the uterus, restoring IGFBP1 expression by injecting Igfbp1-overexpression lentiviruses rescued embryonic resorption. These data indicated that NR5A1 was indispensable for endometrial decidualization and that the NR5A1 reduction in secretory endometrium and early decidua may lead to URSA.

Keywords: IGFBP1; NR5A1; decidual stromal cells; decidualization; endometrial stromal cells; unexplained recurrent spontaneous abortion.

PubMed Disclaimer

Similar articles

See all similar articles

References

    1. R. Bender Atik, O. B. Christiansen, J. Elson, et al., “ESHRE Guideline: Recurrent Pregnancy Loss: An Update in 2022,” Human Reproduction Open 2023 (2023): hoad002.
    1. D. M. Zhu, H. J. Zou, J. X. Liu, et al., “Inhibition of HMGB1 Ameliorates the Maternal‐Fetal Interface Destruction in Unexplained Recurrent Spontaneous Abortion by Suppressing Pyroptosis Activation,” Frontiers in Immunology 12 (2021): 782792.
    1. N. Meng, Q. Yang, Y. P. He, et al., “Decreased NDRG1 Expression Is Associated With Pregnancy Loss in Mice and Attenuates the In Vitro Decidualization of Endometrial Stromal Cells,” Molecular Reproduction and Development 86, no. 9 (2019): 1210–1223.
    1. B. A. Lessey and S. L. Young, “What Exactly Is Endometrial Receptivity?,” Fertility and Sterility 111, no. 4 (2019): 611–617.
    1. J. Cha, X. F. Sun, and S. K. Dey, “Mechanisms of Implantation: Strategies for Successful Pregnancy,” Nature Medicine 18, no. 12 (2012): 1754–1767.

MeSH terms

Substances

LinkOut - more resources