Medroxyprogesterone acetate modulates remodeling, immune cell census, and nerve fibers in the cervix of a mouse model for inflammation-induced preterm birth.
To determine whether a progestational agent can modify inflammation-induced preterm cervical ripening, mice on day 15 of gestation were given an intrauterine injection of (1) saline, (2) lipopolysaccharide, (3) an intramuscular injection of medroxyprogesterone acetate alone prior to lipopolysaccharide, or (4) medroxyprogesterone acetate alone. Cervices were obtained 6 hours later, then fixed, sectioned, and processed to stain collagen structure or to identify immune cells or nerve fibers. Cervical remodeling was induced by lipopolysaccharide treatment compared with that in saline controls, an effect blocked by medroxyprogesterone acetate pretreatment. Moreover, lipopolysaccharide reduced macrophages and enhanced neutrophils in the cervix, effects also forestalled by medroxyprogesterone acetate pretreatment. Although the density of nerve fibers was not altered by lipopolysaccharide, medroxyprogesterone acetate reduced innervation in the cervix. Thus, progestational treatment forestalls the inflammation-induced reduction in collagen structure and immune cell traffic through a mechanism that is independent of nerve fiber density. These findings raise the possibility that progestational treatment may regulate ripening of the cervix early in the process leading to preterm birth.
Yellon
Steven M
SM
Department of Physiology, Pediatrics and Obstetrics/Gynecology, Loma Linda University School of Medicine, Loma Linda, California 92350, USA. syellon@LLU.edu
Ebner
Charlotte A
CA
Elovitz
Michal A
MA
D000818:Animals; D020070:Cervical Ripening / Q000187:drug effects*; D002584:Cervix Uteri / Q000187:drug effects* / Q000276:immunology / Q000294:innervation / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005865:Gestational Age; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007273:Injections, Intramuscular; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D009412:Nerve Fibers / Q000187:drug effects*; D020556:Neutrophil Infiltration / Q000187:drug effects; D011247:Pregnancy; D047928:Premature Birth / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D011372:Progestins / Q000008:administration & dosage / Q000494:pharmacology*
D008070:Lipopolysaccharides; D011372:Progestins; D003094:Collagen; D017258:Medroxyprogesterone Acetate