Molecular Regulation of Parturition: A Myometrial Perspective.
The molecular mechanisms that maintain quiescence of the myometrium throughout most of pregnancy and promote its transformation to a highly coordinated contractile unit culminating in labor are complex and intertwined. During pregnancy, progesterone (P4) produced by the placenta and/or ovary serves a dominant role in maintaining myometrial quiescence by blocking proinflammatory response pathways and expression of so-called "contractile" genes. In the majority of placental mammals, increased uterine contractility near term is heralded by an increase in circulating estradiol-17β (E2) and/or increased estrogen receptor α (ERα) activity and a sharp decline in circulating P4 levels. However, in women, circulating levels of P4 and progesterone receptors (PR) in myometrium remain elevated throughout pregnancy and into labor. This has led to the concept that increased uterine contractility leading to term and preterm labor is mediated, in part, by a decline in PR function. The biochemical mechanisms for this decrease in PR function are also multifaceted and interwoven. In this paper, we focus on the molecular mechanisms that mediate myometrial quiescence and contractility and their regulation by the two central hormones of pregnancy, P4 and estradiol-17β. The integrative roles of microRNAs also are considered.
Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9038.
Nora E
NE
Renthal
Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9038.
Koriand'r C
KC
Williams
Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9038.
Alina P
AP
Montalbano
Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9038.
Chien-Cheng
CC
Chen
Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9038.
Lu
L
Gao
Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9038 Department of Obstetrics-Gynecology, North Texas March of Dimes Birth Defects Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9038.
Carole R
CR
Mendelson
D000818:Animals; D004958:Estradiol / Q000502:physiology; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000502:physiology; D009215:Myometrium / Q000502:physiology*; D036801:Parturition / Q000502:physiology*; D011247:Pregnancy; D011374:Progesterone / Q000502:physiology; D014590:Uterine Contraction / Q000502:physiology
D035683:MicroRNAs; D011374:Progesterone; D004958:Estradiol