Krüppel-like factor 12 is a novel negative regulator of forkhead box O1 expression: a potential role in impaired decidualization

Reproductive Biology and Endocrinology

Guijun Yan¹  Haixiang Sun³  Xin Zhen¹  Zhenyu Diao¹  Lijun Ding¹  Jun Xing¹  Chengcai Kong¹  Qun Zhang¹  Yue Jiang¹  Jing Chen¹  Xudong Zhu²  Hui Zhang³ 

[1] Department of Obstetrics and Gynecology, Reproductive Medicine Center, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, Jiangsu, China;College of Science Isotope Laboratory, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China;Reproductive Medicine Center, Drum Tower Clinic Medical College of Nanjing Medical University, Nanjing 210029, Jiangsu, China

关键词: RIF;    Decidualization;    FOXO1;    KLF12;   

Others  :  1224330
DOI  :  10.1186/s12958-015-0079-z

 received in 2015-03-09, accepted in 2015-07-18,  发布年份 2015

【 摘 要 】

Background

Decidualization is a prerequisite for successful implantation and the establishment of pregnancy. Krüppel-like factor 12 (KLF12) is a negative regulator of endometrial decidualization in vitro. We investigated whether KLF12 was associated with impaired decidualization under conditions of repeated implantation failure (RIF).

Methods

Uterine tissues were collected from a mouse model of early pregnancy and artificial decidualization for immunohistochemistry, Western blot and real-time PCR analysis. Reporter gene assays, chromatin immunoprecipitation-PCR and avidin-biotin conjugate DNA precipitation assays were performed to analyze the transcriptional regulation of forkhead box O1 (FOXO1) by KLF12. Furthermore, the protein levels of KLF12 and FOXO1 in patients with RIF were analyzed by Western blot and immunohistochemistry.

Results

KLF12 led to defective implantation and decidualization in the mouse uterine model of early pregnancy and artificial decidualization by directly binding to the FOXO1 promoter region and inhibiting its expression in human endometrial stromal cells. Elevated KLF12 expression was accompanied by decreased FOXO1 expression in the endometria of patients with RIF.

Conclusions

As a novel regulator, KLF12 predominantly controls uterine endometrial differentiation during early pregnancy and leads to implantation failure.

【 授权许可】

   
2015 Zhang et al.

【 图 表 】

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