Prevention of preterm birth by progestational agents: what are the molecular mechanisms?

Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. Electronic address: .
American journal of obstetrics and gynecology (Impact Factor: 3.97). 03/2013; 208(3):223.e1-7. DOI: 10.1016/j.ajog.2013.01.020
Source: PubMed

ABSTRACT Clinically, vaginal progesterone (VP) and 17 alpha-hydroxyprogesterone caproate (17P) have been shown to prevent preterm birth (PTB) in high-risk populations. We hypothesize that treatment with these agents may prevent PTB by altering molecular pathways involved in uterine contractility or cervical remodeling.
Using a mouse model, on embryonic day (E)14-E17 CD-1 pregnant mice were treated with: (1) 0.1 mL of 25 mg/mL of 17P subcutaneously; (2) 0.1 mL of castor oil subcutaneously; (3) 0.1 mL of 10 mg/mL of progesterone in a long-lasting Replens (Lil' Drug Store Products, Inc., Cedar Rapids, IA); or (4) 0.1 mL of the same Replens, with 4 dams per treatment group. Mice were sacrificed 6 hours after treatment on E17.5. Cervices and uteri were collected for molecular analysis.
Exposure to VP significantly increased the expression of defensin 1 compared to Replens (P < .01) on E17.5. Neither VP nor 17P altered the expression of uterine contraction-associated proteins, progesterone-mediated regulators of uterine quiescence, microRNA involved in uterine contractility, or pathways involved in cervical remodeling. In addition, neither agent had an effect on immune cell trafficking or collagen content in the cervix.
Neither VP nor 17P had any effect on the studied pathways known to be involved in uterine contractility or quiescence. In the cervix, neither VP nor 17P altered pathways demonstrated to be involved in cervical remodeling. Administration of VP was noted to increase the expression of the antimicrobial protein defensin 1. Whether this molecular change from VP results in a functional effect and is a key mechanism by which VP prevents PTB requires further study.

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