Role of COX-2 for Successful Embryo Implantation Process: A Mini-review

Abstract

The endometrium undergoes a dynamic proliferation of cells and vascular tissue under the influence of ovarian steroid hormones. Implantation is an essential process in the development of pregnancy, where there is close contact between embryo and uterus, including supposition, adhesion, and invasion. The changes occur in the human endometrium, including endometrial secretion changes, blood vessels, and immune response, leading to the uterine receptivity period. Cyclooxygenase (COX) is an enzyme that plays a role in the metabolic conversion of arachidonic acid to prostaglandins (PG). It is known that Cyclooxygenase-2 (COX-2) plays a key role in the endometrium. COX-2 is essential for blastocyst implantation and decidualization. The deficiency of COX-2, but not COX-1, results in multiple female reproductive failures (including implantation defects). We reviewed the literature on COX-2 and embryonal implantation in the endometrium and its potential mechanisms that lead to physiological implantation. This review aims to identify the essential roles of COX-2 in the successful implantation process, especially in decidualization, implantation, and embryo growth. The regulation of COX-2 expression in endometrial cells is controlled by ovarian steroid hormones (progesterone and estrogen) through the ENaC pathway to regulate the phosphorylation CREB transcription factor. The presentation of COX-2 varies throughout the stage of embryo development.

Oxidative Stress and the Nrf2/PPARγ Axis in the Endometrium: Insights into Female Fertility

“…Inflammation plays both positive and negative roles in female fertility. Physiologically, inflammation is essential for processes like ovulation, menstruation, and implantation [9,18,19]. For instance, controlled inflammatory responses are crucial for the rupture of ovarian follicles during ovulation and for the remodeling of the endometrium during menstruation and implantation [9,19].…”

“…Reduced COX-2 expression is associated with implantation and decidualization failures of human decidua, emphasizing its significance [33]. Physiologically increased COX-2 activity leads to the induction of the expression of chemokines such as interleukin 8 (IL-8), membrane cofactor protein 1 (MCP-1), C-X-C chemokine ligand 1 (CXCL-1), and C-X-C chemokine receptor 4 (CXCR-4), which are an essential part of the cross-talk between the endometrium and the blastocyst, mediating the attachment of embryo to uterine lining [18,34]. Pro-inflammatory and chemotactic cytokines are also necessary for the recruitment and activation of phagocytic cells, which are the main producers of ROS and reactive nitrogen species (RNS) involved in blastocyst implantation [14,[35][36][37].…”

“…Increased levels of PPARγ by elevated OS in the endometrium potentially hinder the implantation process of an embryo [18,112,126]. Increased activity of COX-2 is necessary to facilitate the implantation process by inducing the production of cytokines which are important signalization molecules in the blastocyst-endometrium crosstalk [18]. Decreased expression of COX-2 may also negatively impact decidualization by downregulation of VEGF [3,130].…”

“…to facilitate the implantation process by inducing the production of cytokines whic important signalization molecules in the blastocyst-endometrium crosstalk [18] creased expression of COX-2 may also negatively impact decidualization by downre tion of VEGF [3,130]. The COX-2 expression mediated by the NF-κB is an important acteristic of the implantation process [1].…”