Characterization of topology-, gestation- and labor-related changes of a cassette of myometrial contraction-associated protein mRNA in the pregnant baboon myometrium

Wu, W. X.; Ma, Xinxin; Zhang, Q; Nathanielsz, Peter W.

doi:10.1677/joe.0.1710445

Cited by 8 publications

(2 citation statements)

References 38 publications

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“…Although myometrial activity initially remains relatively quiescent throughout pregnancy, the sensitivity of the uterus to various uterotonins, such as oxytocin and prostaglandins, is increased through the course of pregnancy due to increased respective receptors (Fuchs et al 1983, 1984, Baguma-Nibasheka et al 1998, Gimpl & Fahrenholz 2001, Wu et al 2001 with no further augmentation at labor (Palliser et al 2005). In addition, the uterus increases ten times in weight and the cervix extends ten times in length during pregnancy (Cumningham et al 2001).…”

Section: Discussionmentioning

confidence: 99%

Separate and synergistic effect of progesterone and estradiol on induction of annexin 2 and its interaction protein p11 in pregnant sheep myometrium

Zhang

Wen

2007

Journal of Molecular Endocrinology

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To search for myometrial candidate genes regulated by progesterone, we isolated annexin 2 cDNA by subtractive hybridization and cloning. We also examined the effect of estradiol and/or progesterone, individually or combined, on expressions of annexin 2 and its ligand protein, p11 in pregnant sheep intrauterine tissues. Annexin 2 is a Ca 2C -dependent phospholipid-binding protein which interacts with p11 to form a bivalent heterotetramer. The heterotetramer was indicated in the production of prostaglandins through the regulation of cytosolic phospholipase A2 (cPLA2) and arachidonic acid release. Thus, annexin 2 and p11 could be the important players in Ca 2C signaling and prostaglandin production in uterine smooth muscles. Twenty-two ewes were treated with vehicle (nZ6), or 5 mg estradiol administered intramuscularly twice a day for 2 days (nZ6), or 100 mg progesterone administered intramuscularly twice a day for 14 days (nZ5), or estradiol plus progesterone with 100 mg progesterone administered intramuscularly twice a day for 10 days (nZ5) and then with vehicle for 2 days followed by estradiol for 2 days (5 mg administered intramuscularly twice a day). At 121 days of gestation age (dGA), endometrium, myometrium, placenta, and cervix were obtained under halothane anesthesia. Subtractive hybridization was used to isolate differentially expressed mRNAs from myometrial tissues treated with progesterone, which was confirmed by western blot at protein level. Annexin 2 and p11 interaction was validated by immunoprecipitation and their expressions in intrauterine tissues were determined by western blot analysis. Data were analyzed by ANOVA. A cDNA clone from myometrial-subtracted library representing differentially expressed mRNA in the pregnant sheep myometrium with progesterone treatment was identified as annexin 2 by sequence analysis and BLASTN search. Annexin 2 was present in both cytosolic and membrane-associated fractions of intrauterine tissues. In contrast, p11 was detectable only in myometrial cytosolic fraction. Both annexin 2 and p11 significantly increased in myometrial cytosolic fraction after progesterone or progesterone plus estradiol treatment. Furthermore, estradiol and progesterone combined had a more profound effect on induction of annexin 2 than progesterone alone. Annexin 2 was immunoprecipitated specifically by p11 antibody from the myometrium. This study indicates that progesterone may play an important role in the control of myometrial contractility by modifying protein expression associated with Ca 2C and prostaglandin signaling systems during pregnancy. Enhanced expression of myometrial annexin 2 in progesterone plus estradiol group supports our hypothesis that estrogen's stimulation is optimized by progesterone's priming in the pregnant sheep uterus.

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Section: Discussionmentioning

confidence: 99%

Separate and synergistic effect of progesterone and estradiol on induction of annexin 2 and its interaction protein p11 in pregnant sheep myometrium

Zhang

Wen

2007

Journal of Molecular Endocrinology

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“…Expression of OXTR and CX43, which are known to be up-regulated near term in a variety of species (Fuchs et al 1984;Chow and Lye 1994;Ou et al 1997Ou et al , 1998Sparey et al 1999;Wu et al 2001), are temporally up-regulated in mouse and human myometrium as ZEB1/2 expression declines (Renthal et al 2010). CX43 is responsible for the formation of gap junctions in the myometrium, which mediate the intercellular communication required for the synchronous myometrial contractions necessary for successful labor.…”

Section: P 4 /Pr Maintains Myometrial Quiescence Throughout Pregnancymentioning

confidence: 99%

Molecular Regulation of Parturition: A Myometrial Perspective

Renthal

Williams

Montalbano

et al. 2015

Cold Spring Harb Perspect Med

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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 (P 4 ) 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-17b (E 2 ) and/or increased estrogen receptor a (ERa) activity and a sharp decline in circulating P 4 levels. However, in women, circulating levels of P 4 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, P 4 and estradiol-17b. The integrative roles of microRNAs also are considered.

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