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Progesterone Receptor Membrane Component 1, 2 and Glucocorticoid Receptor mRNA Expression in Fetal Membranes and Its Association with Preterm Births
Abstract Number: BP-1
Abstract Type: Original Research
Introduction. Preterm birth (PTB), defined as a gestational age <37 weeks, is a leading cause of neonatal mortality and morbidity. Preterm premature rupture of membranes (PPROM) is the leading identifiable cause of PTB. Progesterone receptor signaling plays an important role in establishing and maintaining pregnancy. Fetal membranes (FM) express membrane associated progesterone receptors – progesterone receptor membrane component (PGRMC) 1 and 2 and the glucocorticoid receptor (NR3C1) which may also mediate progesterone’s action. Furthermore PGRMC1, 2 and NR3C1 regulate cellular apoptosis, cell cycling, prostaglandin synthesis and collagen metabolism – all molecular mechanisms which may lead to PTB. However, there is a paucity of data on the mRNA expression of these receptors in FM in the different PTB phenotypes. Our aim was to determine if PGRMC1, 2 and NR3C1 mRNA levels were differentially expressed in the FM of the different PTB clinical phenotypes when compared with term no labor (TNL) patients.
Methods: We identified fetal membrane samples prospectively collected from 50 patients in the Adverse Pregnancy Outcomes: Blood and Tissue Repository who were grouped into the following groups (10 samples per clinical group): TNL, term labor (TL), preterm no labor (PTNL), preterm labor (PTL) and PPROM. PGRMC1, 2 and NR3C1 mRNA levels were quantified using RT-qPCR from the FM samples and normalized to the geometric mean of two housekeeping genes – GAPDH and RPL30 and presented as the 2-ΔΔ CT. Demographic data and obstetric data were summarized using descriptive statistics. A linear regression model was used to test the clinical group effect on mRNA expression data for each gene, using the TNL group as reference with covariate adjustment for race/ ethnicity, prior history of PTB and the presence of clinical chorioamnionitis.
Results: We excluded one patient from PTNL group due to missing expression data and analyzed data for 49 patients. When compared with the TNL group, PGRMC1,2 and NR3C1 mRNA expression were significantly reduced in the FM of PTL patients, PGRMC1 and NR3C1 mRNA expression were significantly reduced in the FM of patients with PPROM and PGRMC1 mRNA expression was significantly reduced in the FM of TL patients when adjusted for covariates (Table).
Conclusion: A reduction in PGRMC1, 2 and NR3C1 mRNA expression in FM was associated with PTL and PPROM. Regulation of the expression of these genes may shed further light on mechanisms involved in PTB.