Isoform-Specific Compensation of Cyclooxygenase (Ptgs) Genes during Implantation and Late-Stage Pregnancy

Abstract

The participation of cyclooxygenase (COX) in embryo implantation and parturition has been studied extensively. However, the distinct role of the two COX isoforms in these processes still remains unclear. Using three characterized mouse lines where the Ptgs1 and Ptgs2 genes substitute for one another, this study focused on the reproductive significance of their distinct roles and potential biological substitution. In both non-gravid and gravid uteri, the knock-in COX-2 is expressed constitutively, whereas the knock-in COX-1 is slightly induced in early implantation. The delayed onset of parturition previously found in COX-1 null mice was corrected by COX-2 exchange in COX-2>COX-1 mice, with normal term pregnancy, gestation length and litter size. In contrast, loss of native COX-2 in COX-1>COX-2 mice resulted in severely impaired reproductive functions. Knock-in COX-1 failed to substitute for the loss of COX-2 in COX-1>COX-2 mice during implantation, indicating that COX-1 may be replaced by COX-2, but not vice versa. A panel of prostaglandins detected in uterus and ovary demonstrates that prostaglandin biosynthesis preferentially depends on native COX-1, but not COX-2. More interestingly, preferential compensations by the COX isoforms were sustained despite weak dependency on their role in prostaglandin biosynthesis in the uterus and ovary.

Effect of NETs/COX-2 pathway on immune microenvironment and metastasis in gastric cancer

“…As a member of the tumor inflammatory microenvironment, COX-2 is localized to the nuclear membrane and endoplasmic reticulum ( 65 ), and it plays a critical part in many cancers ( 66 – 69 ). For example, COX-2 can regulate intestinal cell adhesion and up-regulate the activity of matrix metalloproteinase to enhance metastasis ( 70 , 71 ).…”

Embryo–Uterine Cross-Talk: Exploration of the Immunomodulatory Mechanism in Buffalo

“…It initiates the process of biosynthesis through a different family of bioactive lipid mediators known as PGs, such as PGD2 , PGE2 , PGF2α , PGI2 and thromboxane (TxA2), in a cell-type restricted fashion [ 35 ]. PTGS2 is also known to be essential for implantation, corpus luteum development, fetus growth and development [ 36 ]. Thus, the expression of PTGES along with the secretion of PGE2 was stimulated in UECs by early-developing embryos [ 15 ].…”

Natural Mating Differentially Triggers Expression of Glucocorticoid Receptor (NR3C1)-Related Genes in the Preovulatory Porcine Female Reproductive Tract

“…Thus, our results could indicate that natural mating leads to a downregulation of PTGS2 in the reproductive tract from cervix to isthmus, while upregulating PTGS1 in some tissues. Recent evidence of a specific PTGS1-PTGS2 compensation mechanism involving these two genes indicates they may be responsible for prostaglandin synthesis in reproductive tissues [70]. Also, the observed increase in PLA24GB gene expression, responsible for the ARA precursor of prostaglandins, in the ampulla by natural mating as well as by AI-treatments (semen-AI and SP-AI) might be related to the expression of the oviductal phospholipase A2 gene (PLA2G4B) close to the fertilization site and may be specifically stimulated by the first seminal plasma portion.…”