Cervix remodeling and parturition in the rat: lack of a role for hypogastric innervation

Abstract

The hypogastric nerve is a major pathway innervating the uterine cervix, yet its contribution to the processes of cervical ripening and parturition is not known. The main objective of this study was to determine the effect of hypogastric nerve transection on remodeling of the cervix and timing of birth. As an initial goal, processes associated with remodeling of the peripartum cervix were studied. The cervix was obtained from time-dated pregnant rats on days 15, 19, 21, and 21.5 of pregnancy, and post partum on the day of birth (day 22). The cervix was excised, post-fixed overnight, and sections stained to evaluate collagen content and structure or processed by immunohistochemistry to identify macrophages or nerve fibers. The census of macrophages and density of nerve fibers in the cervix peaked on day 21, the day before birth, and then declined post partum. These results replicate in time course and magnitude previous studies in mice. To address the main objective, the hypogastric nerve was bilaterally transected on day 15 post-breeding; sham-operated rats served as controls. Pups were born in both groups at normal term. Transection of the hypogastric nerves did not affect remodeling of collagen or the census of macrophages or the density of nerve fibers in the cervix. These findings support the contention that enhanced innervation and immigration of immune cells are associated with remodeling of the cervix and parturition, but that a neural pathway other than the hypogastric nerve may participate in the process of cervical ripening.

Transection of the Pelvic or Vagus Nerve Forestalls Ripening of the Cervix and Delays Birth in Rats1

“…Procedures used to stain cervical sections with picrosirius red for analysis of collagen content and structure, as well as to enumerate cell nuclei, macrophages, and nerve fibers, using immunohistochemistry and image analyses have been previously detailed [4,5,40]. Briefly, the optical density (OD) of polarized light from birefringence of type I collagen [13] from picrosirius red-stained sections of cervix was normalized to the number of cell nuclei/area for each rat, to account for the hypertrophy of tissue in pregnant rat cervix (less that of the extracellular matrix per field of view).…”

“…Photomicrographs of birefringent polarized light were converted to grayscale images. Regions of reduced collagen content and scattered fibrils were inversely related to OD as previously described [5,40] (details of NIH Image J analyses are in Materials and Methods). Compared to OD of nonpregnant controls, OD was significantly increased (less collagen content and structure) in cervix of prepartum [71] and postpartum (PP) groups (P , 0.05; ANOVA, F ¼ 5.984, df ¼ 11).…”

“…In contrast to the uterus, which is relatively denervated with pregnancy [1][2][3], the density of nerve fibers in the cervix is increased manifold by the day before birth in rodents [4,5] and in women is sustained during the peripartum period [6,7]. The cervix receives sympathetic innervation from the hypogastric nerve [8,9], as well as parasympathetic projections through the pelvic and vagus nerves [10][11][12][13].…”

“…Understanding the contribution of innervation to the process of parturition comes from evidence that indicates that transection of the hypogastric nerve, i.e., sympathetic innervation, does not affect cervical ripening or birth in rats [4,5]. By contrast, it has been known for a long time that input from the pelvic nerve is involved in the process of parturition at term.…”

Remodeling of the Cervix and Parturition in Mice Lacking the Progesterone Receptor B Isoform

“…As term approaches, remodeling of the cervix is characterized by reduced density of cell nuclei, degradation of extracellular matrix collagen content and structure, and immigration of immune cells [17][18][19][20]. By the day before birth, immune cells have immigrated into the stroma and perimetrium of the cervix in mice [21,22] and rats [23,24]. Evidence in primates also suggests that these characteristics of inflammation are part of the process that remodels the cervix [25][26][27].…”