Submitted June 12, 2007
Returned for revision July 13, 2007
Accepted September 7, 2007
Pregnancy
Parturition and Recruitment of Macrophages in Cervix of Mice Lacking the Prostaglandin F Receptor
Steven M. Yellon *,
Charlotte A. Ebner ,
and
Yukihiko Sugimoto
* To whom correspondence should be addressed. E-mail: syellon{at}som.llu.edu.
Abstract
Parturition does not occur in transgenic mice lacking the prostaglandin F receptor (Ptgfr-/-) because luteolysis is forestalled and progesterone production persists. Parturition does not occur in transgenic mice lacking the prostaglandin F receptor (Ptgfr-/-) because luteolysis is forestalled and progesterone production persists. Ovariectomy of pregnant Ptgfr-/- mice leads to a decline in circulating progesterone and delivery of live pups. The objective of the present study was to test the hypothesis that immigration of macrophages and increased innervation of the cervix of Ptgfr-/- mice was associated with ripening and parturition. The cervix of pregnant Ptgfr-/- mice was studied on days 15-21 post-breeding; additional groups were ovariectomized on day 19 of pregnancy and the cervix obtained on day 20 of pregnancy before birth or the next day at about 24 h after birth. On days 18-19 of pregnancy, macrophage numbers and nerve fiber density increased more than 3-fold compared to findings in non-pregnant or days 15 or 21 pregnant Ptgfr-/- mice. The magnitude and time course of these changes were comparable to those found in wild-type controls that delivered on day 19 post-breeding. Thus, the mechanism regulating macrophage immigration, innervation, and cervical remodeling is similar in Ptgfr-/- mice with delayed parturition as in wild-type controls that deliver at term. By contrast, ovariectomy forestalled the decrease in cervical macrophages in Ptgfr-/- mice. By day 21 post-breeding, macrophage numbers more than double after ovariectomy, relative to that found in pregnant Ptgfr-/- mice, while nerve fiber density was the same irrespective of birth. Density of collagen structure in these mice directly matched macrophage traffic in the cervix. The findings indicate that the prostaglandin F2alpha receptor and progesterone withdrawal are a necessary part of the final common pathway for ripening of the cervix and the process of parturition.
Key words:
Cervix •
Neuropeptides •
Parturition •
Progesterone •
macrophage
