Ovulation provides excessive coagulation and hepatocyte growth factor signals to cause postoperative intraabdominal adhesions

• Published in: iScience Vol. 27; no. 6; p. 109788
• Main Authors: Seenan, Vaishnavi, Hsu, Che-Fang, Subramani, Kanchana, Chen, Pao-Chu, Ding, Dah-Ching, Chu, Tang-Yuan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.06.2024; Elsevier
• Subjects: Cellular physiology; Female reproductive endocrinology; Surgery; Female reproductive endocrinology; Cellular physiology; Surgery
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.109788

Postoperative adhesions show a higher occurrence in females aged 16–60, especially after pelvic surgeries. This study explores the role of ovulation in adhesion formation in mice. Ovarian surgery in mice with normal- or super-ovulation led to pronounced adhesions, whereas ovulation-defective Pgr-KO mice showed minimal adhesions. Specifically, exposure to ovulatory follicular fluid (FF) markedly increased the adhesion. The hazardous exposure time window was one day before to 2.5 days after the surgery. Mechanistically, early FF exposure triggered adhesions via the blood coagulation cascade, while later exposure relied on the HGF/cMET signaling pathway. Prophylactic administration of a thrombin inhibitor pre-operatively or a cMET inhibitor postoperatively effectively mitigated FF-induced adhesions, while COX inhibitor treatment exhibited no discernible effect. These findings underscore ovulation as a pivotal factor in the development of pelvic wound adhesions and advocate for targeted preventive strategies such as c-MET inhibition, scheduling surgeries outside the ovulatory period, or employing oral contraceptive measures. [Display omitted] •Incidence and severity of postoperative adhesions highly depend on exposure of wound to ovulatory follicular fluid (FF)•FF exposure promotes wound adhesions in a hazardous time frame of 1 day before to 2.5 days after surgery•Coagulation cascade and HGF signals are responsible for early- and late-exposure risk, respectively•Ovulation-caused wound adhesions can be prevented by avoiding surgery at the ovulation time, or by giving a cMET inhibitor Surgery; Cellular physiology; Female reproductive endocrinology