Are classic inflammatory macrophages involved in progesterone receptor agonist-induced prevention of preterm birth in mice?
- Steven Yellon, Professor of Physiology, Loma Linda School of Medicine
- Michael Kirby, Professor of Anatomy, Loma Linda School of Medicine
Prepartum remodeling of the cervix reflects extracellular collagen degradation, cellular hypertrophy, and macrophage immigration in association with dilation and loss of structure (Trends Endocrinol Metab 21:6,2010). Progesterone receptor (PR) agonists forestall these characteristics (Biol Reprod 87:106,2012), but little is known about activities by resident macrophages during the remodeling process. This study tested the hypothesis that inflammatory macrophage activity increases in the cervix before term and with progesterone withdrawal-induced preterm birth. Pregnant mice were Sham-operated or ovariectomized (Ovx) on postbreeding day 16. Ovx mice were injected with vehicle (Ovx), pure PR agonist (Ovx+R5020), or medroxyprogesterone acetate (Ovx+MPA, a PR/glucocorticoid receptor agonist). Mice were killed on the day before or of birth. The cervix was sectioned, stained for CCR7 (indicative of classic inflammatory macrophage activity; J Immunol 176:5153, 2006), and counterstained with methyl green (nucleus stain used to determine local cell density). Ovx controls gave birth early on day 17 postbreeding (24h post-Ovx) while Sham, as well as Ovx+R5020 and Ovx+MPA mice gave birth at term (day 18) or later. Using Bright field microscopy, indications are that the number of CCR7-stained cells in the cervix increased by the day before birth in Sham (D17) and R5020-treated Ovx mice, but were unchanged in Ovx or Ovx+MPA mice. Findings suggest that classic inflammatory activity by macrophage, as indicated by increased numbers of CCR7-stained cells before term in Sham and Ovx+R5020 mice, may be enhanced in the cervix in association with remodeling before birth. No change in CCR7 stained cells after Ovx or in Ovx+MPA mice raises the possibility that preterm birth may not involve classic inflammatory activity by macrophages. Further study is needed to address the possibility that a pure PR receptor agonist may have therapeutic value to forestall early remodeling of the cervix and delay preterm birth.