miR-149-PARP-2 Signaling Regulates E-cadherin and N-cadherin Expression in the Murine Model of Endometrium Receptivity

• Published in: Reproductive sciences (Thousand Oaks, Calif.) Calif.), 2022-03, Vol.29 (3), p.975-992
• Main Authors: Verma, Raj Kumar, Soni, Upendra Kumar, Chadchan, Sangappa Basanna, Maurya, Vineet Kumar, Soni, Mohini, Sarkar, Sudarsan, Pratap, J. Venkatesh, Jha, Rajesh Kumar
• Format: Article
• Language: English
• Subjects: Animals; Cadherins - metabolism; Embryo Implantation - physiology; Embryology; Endometrium - metabolism; Female; Medicine; Medicine & Public Health; Mice; MicroRNAs - metabolism; Obstetrics/Perinatology/Midwifery; Poly(ADP-ribose) Polymerases - metabolism; Pregnancy; Reproductive Biology: Original Article; Reproductive Medicine; Signal Transduction
• ISSN: 1933-7191; 1933-7205
• DOI: 10.1007/s43032-021-00710-3

Cadherins play an essential role in the attachment of the blastocyst to the endometrium, a process known as endometrial receptivity. Loss of E-cadherin expression is essential during the process, while the expression level of the other cadherin, N-cadherin, has been reported to be altered in cases of infertility. Both E-cadherin and N-cadherin can be regulated by members of the PARP family. Specifically, PARP-2, which is under the epigenetic control of miR-149, has been observed to promote E-cadherin expression in other human cells. We investigated the roles of E-cadherin and N-cadherin in endometrial receptivity using mouse models for normal endometrial receptivity, pseudopregnancy, and LPS-induced endometrial receptivity failure. E-cadherin and phosphorylated E-cadherin were predominantly expressed during pre-receptive stages as well as in the implantation site of the receptive stage, which were observed reduced during the later stages of implantation in both implantation and non-implantation regions, while N-cadherin was detected only at pre-receptive stages. E-cadherin and N-cadherin were also seen in the uterus during pseudopregnancy, showing a downregulation trend during receptive and post-receptive stages. LPS-induced failed endometrial receptivity showed upregulation of E-cadherin and downregulation of N-cadherin. The E-cadherin expression promoter, GSK-3, was lost and its suppressor, SLUG was upregulated during normal course of endometrial receptivity in mouse model, while GSK-3 was increased during LPS-induced failed embryo implantation. In an in vitro model of embryo implantation, E-cadherin expression is promoted by PARP-2 and regulated by miR-149 epigenetically in human endometrium epithelial cells. In conclusion, E-cadherin is predominantly expressed during pre-receptive stage and promoted by PARP-2, which is regulated by miR-149 in the endometrial epithelial cells.