FOXO3a is essential for murine endometrial decidualization through cell apoptosis during early pregnancy

• Published in: Journal of cellular physiology Vol. 234; no. 4; pp. 4154 - 4166
• Main Authors: Long, Jing, Yang, Cheng‐Shun, He, Jun‐Lin, Liu, Xue‐Qing, Ding, Yu‐Bin, Chen, Xue‐Mei, Tong, Chao, Peng, Chuan, Wang, Ying‐Xiong, Gao, Ru‐Fei
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2019
• Subjects: Abortion, Spontaneous - metabolism; Abortion, Spontaneous - pathology; Animals; Apoptosis; Decidua; decidualization; Embryo Implantation; Embryos; Endometrium; Endometrium - metabolism; Female; Forkhead Box Protein O3 - genetics; Forkhead Box Protein O3 - metabolism; Forkhead protein; FOXO3 protein; FOXO3a; Gene expression; Humans; Implantation; Mice; Pregnancy; Ribonucleic acid; RNA; Signal Transduction; siRNA; Stromal cells; Stromal Cells - metabolism; Surgical implants; Time Factors; Transcription factors; Up-Regulation; Uterus; endometrium; apoptosis; FOXO3a; decidualization
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.27167

Embryo implantation is essential for normal pregnancy, and the process of decidualization is critical for embryo implantation. However, the mechanism of decidualization during early pregnancy is still unknown. Forkhead box O3a (FOXO3a) is the most important functional transcription factor of the forkhead box family and is a highly conserved transcription factor of apoptosis‐related genes. In the mouse uterus, FOXO3a was found to be expressed regularly from Days 1–7 of early pregnancy. Upon further exploration, it was found that FOXO3a was expressed at significantly higher levels at the implantation site than at the interimplantation site on Days 5–7 of pregnancy. Under artificial decidualization, FOXO3a was highly expressed in the first and second decidual zones. After decidualization, the expression of FOXO3a was significantly increased both in vivo and vitro. In primary stromal cells, apoptosis was reduced by decreased expression of FOXO3a after inducing decidualization. Moreover, when FOXO3a‐small interfering RNA was transfected into the uteri of mice, the expression of decidualization‐ and apoptosis‐related factors was impaired. Thus, FOXO3a might play an important role in decidualization during early pregnancy, and cell apoptosis might be one of pathways for FOXO3a‐regulated decidualization. Embryo implantation is essential for normal pregnancy, and the process of decidualization is critical for embryo implantation. The expression of forkhead box O3a (FOXO3a) was significantly increased when decidualization both in vivo and vitro. FOXO3a might play an important role in decidualization during early pregnancy.