Yellon Steven M, Burns Alexandra E, See Jennifer L, Lechuga Thomas J, Kirby Michael A
Department of Physiology, Loma Linda University School of Medicine, Loma Linda, California, USA.
Biol Reprod. 2009 Jul;81(1):1-6. doi: 10.1095/biolreprod.108.074997. Epub 2009 Feb 18.
Prepartum cervical ripening is associated with remodeling of collagen structure and with inflammation. Progesterone withdrawal is critical for parturition, but the effects of progesterone decline on cervical morphology are unknown. The present study tested the hypothesis that progesterone withdrawal promotes processes associated with remodeling of the cervix. Adult, virgin, female C57BL/6 mice received silastic capsules with oil vehicle or estradiol plus progesterone to parallel concentrations in circulation during pregnancy. After 17 days of estradiol and progesterone treatment, the progesterone implant was removed from one group. Mice in each group were killed 15, 18, or 19 days after placement of capsules. Sections of cervix were stained for collagen, and the densities of macrophages, neutrophils, and area with nerve fibers were assessed. Treatment with gonadal steroids promoted hypertrophy of the cervix, as well as reduced collagen and increased area with nerve fibers compared with vehicle-treated controls. Removal of the progesterone capsule did not affect hypertrophy or innervation, but it did reduce collagen. By contrast, significantly more macrophages and neutrophils were present in the cervix on Days 18 and 19 (i.e., by 24 and 48 h after withdrawal of the progesterone capsule); the immune cell census was equivalent to that in vehicle controls. Findings indicate that gonadal steroids, comparable to those during pregnancy, promote hypertrophy and suppress immigration of immune cells in the cervix. Therefore, in a nonpregnant murine model for parturition, progesterone withdrawal is suggested to recruit immune cells and processes that remodel the cervix.
产前宫颈成熟与胶原蛋白结构重塑及炎症相关。孕酮撤退对分娩至关重要，但孕酮水平下降对宫颈形态的影响尚不清楚。本研究检验了孕酮撤退促进与宫颈重塑相关过程的假说。成年未孕雌性C57BL/6小鼠接受含油载体或雌二醇加孕酮的硅橡胶胶囊，以模拟孕期循环中的浓度。在雌二醇和孕酮治疗17天后，从一组小鼠中取出孕酮植入物。每组小鼠在植入胶囊后15、18或19天处死。取宫颈切片进行胶原蛋白染色，并评估巨噬细胞、中性粒细胞密度及神经纤维面积。与接受载体治疗的对照组相比，性腺类固醇治疗可促进宫颈肥大，减少胶原蛋白含量，并增加神经纤维面积。取出孕酮胶囊并不影响宫颈肥大或神经支配，但可减少胶原蛋白含量。相比之下，在第18天和第19天（即取出孕酮胶囊后24小时和48小时），宫颈中出现了明显更多的巨噬细胞和中性粒细胞；免疫细胞计数与载体对照组相当。研究结果表明，与孕期相当的性腺类固醇可促进宫颈肥大并抑制免疫细胞向宫颈迁移。因此，在非孕小鼠分娩模型中，孕酮撤退被认为可募集免疫细胞及参与宫颈重塑的过程。
