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Fetal Membranes From Term VAginal Deliveries Have a Zone of Weakness Exhibiting Characteristics of Apoptosis and Remodeling

Vishal Pandey, MD

Bradley Stetzer, MD

Brian M. Mercer, MD

Deepak Kumar, MD

Robert M. Moore, MS

Jennifer Fox, BS

Raymond W. Redline, MD

Joseph M. Mansour, PhD

Department of Pediatrics, MetroHealth Medical Center (MHMC), Case Western Reserve University (CWRU), Cleveland, Ohio; Department of Reproductive Biology, MHMC, CWRU, Cleveland, Ohio; Institute Pathology, CWRU School of Medicine, University Hospitals of Cleveland, Cleveland, Ohio; Department of Aerospace and Mechanical Engineering, CWRU, Cleveland, Ohio

John J. Moore, MD

Department of Pediatrics, MetroHealth Medical Center (MHMC), Case Western Reserve University (CWRU), Cleveland, Ohio; Department of Reproductive Biology, MHMC, CWRU, Cleveland, Ohio; Institute Pathology, CWRU School of Medicine, University Hospitals of Cleveland, Cleveland, Ohio; Department of Aerospace and Mechanical Engineering, CWRU, Cleveland, Ohio; Division of Neonatology, MetroHealth Medical Center, 2500 MetroHealth Dr., Cleveland, OH 44109; jmoore{at}metrohealth.org

Background: Recently we identified a weak zone in term, pre-labor (repeat Cesarean section) human fetal membranes (FM) overlying the cervix with biochemical characteristics suggestive of apoptosis and collagen remodeling. We suggested that this weak zone is the FM rupture initiation site. Vaginally delivered patients have a weak zone in their FM overlying the cervix; a comparable weak zone lies adjacent to the tear line in FM after spontaneous rupture (SROM).

Methods: FM From vaginally delivered patients with artificial rupture (AROM) and SROM were collected. FM of AROM patients were marked per agina to identify the FM zone overlying the cervix. Postpartum FM were cut, strength tested and piece strengths were remapped to their former location on a three-dimensional model. A 10-cm diameter zone centered on the marked area (AROM), or defined weak zone (SROM) was compared with the remaining FM.

Results: AROM FM exhibit a para-cervical weak zone. SROM FM exhibit a comparable zone on the tear line. The mean rupture strength within weak zones was 60% of the remaining membranes (P < .001). AROM and SROM FM weak zones both exhibit increased matrix metalloproteinase 9, increased poly (ADP-ribose) polymerase I cleavage, decreased tissue inhibitor of metalloproteinase 3 protein, and histology consistent with remodeling and apoptosis.

Conclusion: Vaginally delivered AROM FM contain a weak zone overlying the cervix. Vaginally delivered ASORM FM contain a weak zone adjacent to the tear line that exhibits biochemical and mechanical characteristics suggestive of collagen remodeling and apoptosis comparable to those of the AR FM weak zone.

Key Words: Fetal membranes • weak zone • collagen remodeling • apoptosis • MMP-9 • TIMP3 • PARP1

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