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Prostaglandin-Endoperoxide Synthase 2 (PTGS2) in the Oviduct: Roles in Fertilization and Early Embryo Development.

ABSTRACT: The mammalian oviduct is a dynamic organ where important events such as final maturation of oocytes, transport of gametes, sperm capacitation, fertilization, embryo development, and transport take place. Prostaglandin-endoperoxide synthase 2 (PTGS2), also known as cyclooxygenase 2 (COX-2), is the rate-limiting enzyme in the production of prostaglandins (PGs) and plays an essential role during early pregnancy, including ovulation, fertilization, implantation, and decidualization. Even though the maternal-embryo communication originates in the oviduct, not many studies have systemically investigated PTGS2 signaling during early development. Most of the studies investigating implantation and decidualization processes in Ptgs2-/- mice employed embryo transfer into the uterus, thereby bypassing the mammalian oviduct. Consequently, an understanding of the mechanistic action as well as the regulation of PTGS2 and derived PGs in oviductal functions is far from complete. In this review, we aim to focus on the importance of PTGS2 and associated PGs signaling in the oviduct particularly in humans, farm animals, and laboratory rodents to provide a broad perspective to guide further research in this field. Specifically, we review the role of PTGS2-derived PGs in fertilization, embryo development, and transport. We focus on the actions of ovarian steroid hormones on PTGS2 regulation in the oviduct. Understanding of cellular PTGS2 function during early embryo development and transport in the oviduct will be an important step toward a better understanding of reproduction and may have potential implication in the assisted reproductive technology.

SUBMITTER: Anamthathmakula P

PROVIDER: S-EPMC7901659 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundResection of colorectal cancer liver metastasis (CRCLM) with curative intent has long-term benefit in ~40% of cases. Prognostic biomarkers are needed to improve clinical management and reduce futile surgeries. Expression of epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2; also known as cyclooxygenase-2) has been associated with carcinogenesis and survival. We investigated the prognostic value of EGFR and PTGS2 expression in patients with resected CRCLM.MethodsFormalin-fixed paraffin-embedded CRCLM tissue and corresponding primary tumour specimens from a multi-institutional cohort of patients who underwent liver resection between 1990 and 2010 were incorporated into tissue microarrays (TMAs). TMAs were stained for EGFR and PTGS2 by immunohistochemistry. The hazard rate ratio (HRR) for the association between expression in CRCLM and overall survival was calculated using a 500-fold cross-validation procedure.ResultsEGFR and PTGS2 expression could be evaluated in 323 and 351 patients, respectively. EGFR expression in CRCLM was associated with poor prognosis (HRR 1.54; P<0.01) with a cross-validated HRR of 1.47 (P=0.03). PTGS2 expression was also associated with poor prognosis (HRR 1.60; P<0.01) with a cross-validated HRR of 1.63 (P<0.01). Expression of EGFR and PTGS2 remained prognostic after multivariate analysis with standard clinicopathological variables (cross-validated HRR 1.51; P=0.02 and cross-validated HRR 1.59; P=0.01, respectively). Stratification for the commonly applied systemic therapy regimens demonstrated prognostic value for EGFR and PTGS2 only in the subgroup of patients who were not treated with systemic therapy (HRR 1.78; P<0.01 and HRR 1.64; P=0.04, respectively), with worst prognosis when both EGFR and PTGS2 were highly expressed (HRR 3.08; P<0.01). Expression of PTGS2 in CRCLM was correlated to expression in patient-matched primary tumours (P=0.02, 69.2% concordance).ConclusionsEGFR and PTGS2 expressions are prognostic molecular biomarkers with added value to standard clinicopathological variables for patients with resectable CRCLM.

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Prostaglandin-Endoperoxide Synthase 2 (PTGS2) in the Oviduct: Roles in Fertilization and Early Embryo Development.

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