CBLL1 promotes endometrial stromal cell senescence via inhibiting PTEN in recurrent spontaneous abortion

Author:

Liu Xueqing123ORCID,Wei Xiaowei123ORCID,Wu Jiayi123ORCID,Xu Yichi123ORCID,Hu Jianing123ORCID,Qin Chuanmei4ORCID,Chen Cailian5,Lin Yi4ORCID

Affiliation:

1. The International Peace Maternity and Child Health Hospital, School of Medicine Shanghai Jiao Tong University Shanghai China

2. Shanghai Key Laboratory of Embryo Original Diseases Shanghai China

3. Institute of Birth Defects and Rare Diseases, School of Medicine Shanghai Jiao Tong University Shanghai China

4. Department of Obstetrics and Gynecology, the Sixth People's Hospital, School of Medicine Shanghai Jiao Tong University Shanghai China

5. Department of Automation Shanghai Jiao Tong University, Key Laboratory of System Control and Information Processing, Ministry of Education of China Shanghai China

Abstract

AbstractRecurrent spontaneous abortion (RSA) is a common pregnancy‐related disorder. Cbl proto‐oncogene like 1 (CBLL1) is an E3 ubiquitin ligase, which has been reported to vary with the menstrual cycle in the endometrium. However, whether CBLL1 is involved in the occurrence and development of RSA remains unclear. This study aimed to investigate the effects of CBLL1 on RSA. We analyzed the expression of CBLL1 in the decidua of RSA patients, as well as its functional effects on cellular senescence, oxidative stress, and proliferation of human endometrial stromal cells (HESCs). RNA sequencing was employed to identify a key downstream target gene regulated by CBLL1. We found that CBLL1 was upregulated in the decidua of RSA patients. Additionally, overexpression of CBLL1 promoted HESC senescence, increased oxidative stress levels, and inhibited proliferation. Phosphatase and tensin homolog located on chromosome 10 (PTEN) was identified as one of the important downstream target genes of CBLL1. In vivo experiments demonstrated that CBLL1 overexpression in the endometrium caused higher embryo absorption rate in mice. Consequently, elevated CBLL1 expression is a potential cause of RSA, representing a novel therapeutic target for RSA.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

Publisher

Wiley

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