Human Cervical Ripening Is Associated with an Increase in Cervical Inducible Nitric Oxide Synthase Expression1

TLDR

Cervical ripening mechanisms are poorly understood, and the potential role of nitric oxide via NOS expression has not yet been examined in the human cervix. This study aimed to identify NOS isoform–expressing cell types in the cervix and compare their expression during ripening versus the nonpregnant state. Postpartum cervices showed markedly higher inducible NOS immunoreactivity and activity—3.2‑fold greater than controls—primarily in epithelial and stromal cells, while eNOS was confined to endothelium and neuronal NOS was absent, indicating that increased iNOS‑derived NO may contribute to natural cervical ripening.

Abstract

The mechanisms that ultimately regulate cervical ripening during parturition remain largely unknown. A possible role for nitric oxide (NO) has recently emerged; however, the expression of NO synthase (NOS) within the human cervix in the ripening process has not been investigated. The purpose of this study was to identify cell types in the human cervix that contain NOS isoforms and to examine changes in their expression during the ripening process and the nonpregnant state. Inducible NOS (iNOS) immunoreactivity was observed in the epithelial cells and stromal spindle cells in 17 of 20 biopsies from cervices obtained within 10 min postpartum, but in only 4 of 12 nonpregnant controls (p = 0.03). Endothelial NOS (eNOS) immunoreactivity was restricted to vascular endothelia in all sections, whereas neuronal NOS was not detectable. Inducible NOS activity in the postpartum group was 3.2 times that of the control group (p = 0.0005), whereas constitutive NOS activity remained unchanged in both groups (p = 0.222). Competitive reverse transcription-polymerase chain reaction revealed no differences in the expression of iNOS (p = 0.443) or eNOS mRNA (p = 0.409). The existence of iNOS in the human postpartum cervix suggests that increased production of NO, probably induced by cytokines, may be relevant to the process of natural cervical ripening in humans.