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

Vaishnavi Seenan; Che-Fang Hsu; Kanchana Subramani; Pao-Chu Chen; Dah-Ching Ding; Tang-Yuan Chu

doi:10.1016/j.isci.2024.109788

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

iScience. 2024 Apr 18;27(6):109788. doi: 10.1016/j.isci.2024.109788. eCollection 2024 Jun 21.

Authors

Vaishnavi Seenan^{1

2}, Che-Fang Hsu¹, Kanchana Subramani^{1

2}, Pao-Chu Chen³, Dah-Ching Ding^{2

3}, Tang-Yuan Chu^{1

2

3

4}

Affiliations

¹ Center for Prevention and Therapy of Gynecological Cancers, Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan, ROC.
² Institute of Medical Sciences, Tzu Chi University, Hualien 970, Taiwan, ROC.
³ Department of Obstetrics & Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan, ROC.
⁴ Department of Life Sciences, Tzu Chi University, Hualien 970, Taiwan, ROC.

Abstract

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.

Keywords: Cellular physiology; Female reproductive endocrinology; Surgery.