Increased expression of prokineticin 2 and its receptor in endometrium of recurrent implantation failure patients decreased the expression of MMP9 important for decidualization

Abstract

Background Studies have shown that abnormalities in the decidualization process were closely related to recurrent implantation failure (RIF). Prokineticin 2 (PK2) is a secreted protein with angiogenic and tissue remodeling functions but its role in the endometrium is unknown. Methods PK2 levels and its receptor PKR1 mRNA and protein levels in mid-secretory endometrium from normal and RIF women were examined by real-time PCR and western blotting, respectively. The effects of PK2 were evaluated by overexpressed PK2 in immortalized endometrial T-HESC cells using lentivirus vector and found different expression of Matrix metalloproteinase 9(MMP9) and lncRNA LUCAT1 by RNA-sequencing. The ability of PK2 to regulate LUCAT1 and MMP9 was verified in endometrial cells by real-time PCR and western blotting. Results Using endometrial biopsies from normal and RIF patients, we found increased expression of PK2, together with its receptor PKR1 in RIF patients. We then overexpressed PK2 in immortalized endometrial T-HESC cells using lentivirus vector and found decreased expression of Matrix metalloproteinase 9(MMP9), and increased expression of lncRNA LUCAT1. We verified the ability of PK2 to stimulate LUCAT1 and decrease MMP9 in endometrial cells. We further demonstrated that increased expression of a long noncoding RNA LUCAT1 and decreased expression of MMP9 in endometrial biopsies of patients with RIF. Thus, we highlighted the important role of PK2 and its receptor PKR1 in decidualization and RIF. Conclusion Prokineticin 2 and its receptor are important in endometrium decidualization. PK2 may affect endometrial decidualization through the LUCAT1- MMP9 pathway, thereby affecting embryo implantation.

The Long Non-Coding RNA Gene AC027288.3 Plays a Role in Human Endometrial Stromal Fibroblast Decidualization

“…Abnormal expression of some lncRNAs in the endometrium or decidua is associated with fertility or gestational abnormalities such as endometriosis [12][13][14][15], recurrent implantation failure [16], and preeclampsia [17]. Some examples of the potential physiological role of lncRNA's in hESF decidualization so far include HAND2-AS1 [18], MALAT1 [15], ENSG00000230699 (LncSAMD11-1:1, [19], HK2P1 [20], TUNAR [21], LUCAT1 [22], and LINC00473 [23]. Many lncRNAs show differential expression in the mouse endometrium during decidualization [24,25].…”

Deciphering the endometrial immune landscape of RIF during the window of implantation from cellular senescence by integrated bioinformatics analysis and machine learning

“…Perturbations of these key cellular and molecular biological events tend to induce the breakdown of the feto–maternal interface and RIF ( 7 , 8 ), but the underlying mechanisms are poorly understood. Accumulated evidence has suggested a conspicuous link between cellular senescence in peri-implantation endometrium and RIF ( 9 , 10 ). Cellular senescence is a state of permanent cell cycle arrest and manifests with a prominent secretion of various bioactive molecules, including reactive oxygen species, pro-inflammatory cytokines, chemokines, and growth factors, called senescence-associated secretory phenotype (SASP) ( 11 , 12 ).…”