Uterine Stretch and Progesterone Action

Lei, Kaiyu; Chen, Li; Cryar, Benjamin Joseph; Hua, Renyi; Sooranna, Suren R.; Brosens, Jan J.; Bennett, Phillip R.; Johnson, Mark R.

doi:10.1210/jc.2010-2310

Cited by 36 publications

(35 citation statements)

References 44 publications

(46 reference statements)

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“…We found that constant stretch, applied by means of hanging 1 or 3 g weights from tissue strips, had no effect on culture-induced changes in PR isoform expression (Figure 4). This is inconsistent with a previous report where stretch downregulated PR-T and PR-B expression; however, it should be noted that those studies used myometrial cells while our study uses myometrial tissue strips [56]. Previous animal studies suggest that progesterone is responsible for maintaining uterine quiescence and promoting myometrial hyperplasia and hypertrophy to inhibit any increase in uterine wall tension [57–60].…”

Section: Discussioncontrasting

confidence: 85%

“…A previous study using term nonlaboring human myometrium tissue showed that stretch applied to myometrial cells in culture resulted in decreased PR-T and PR-B mRNA expression [56]. We found that constant stretch, applied by means of hanging 1 or 3 g weights from tissue strips, had no effect on culture-induced changes in PR isoform expression (Figure 4).…”

Section: Discussionmentioning

confidence: 58%

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Modulation of Progesterone Receptor Isoform Expression in Pregnant Human Myometrium

Ilicic

Zakár

Paul

2017

BioMed Research International

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Background. Regulation of myometrial progesterone receptor (PR) expression is an unresolved issue central to understanding the mechanism of functional progesterone withdrawal and initiation of labor in women. Objectives. To determine whether pregnant human myometrium undergoes culture-induced changes in PR isoform expression ex situ and, further, to determine if conditions approaching the in vivo environment stabilise PR isoform expression in culture. Methods. Term nonlaboring human myometrial tissues were cultured under specific conditions: serum supplementation, steroids, stretch, cAMP, PMA, PGF2α, NF-κB inhibitors, or TSA. Following 48 h culture, PR-T, PR-A, and PR-B mRNA levels were determined using qRT-PCR. PR-A/PR-B ratios were calculated. Results. PR-T and PR-A expression and the PR-A/PR-B ratio significantly increased in culture. Steroids prevented the culture-induced increase in PR-T and PR-A expression. Stretch blocked the effects of steroids on PR-T and PR-A expression. PMA further increased the PR-A/PR-B ratio, while TSA blocked culture-induced increases of PR-A expression and the PR-A/PR-B ratio. Conclusion. Human myometrial tissue in culture undergoes changes in PR gene expression consistent with transition toward a laboring phenotype. TSA maintained the nonlaboring PR isoform expression pattern. This suggests that preserving histone and/or nonhistone protein acetylation is critical for maintaining the progesterone dependent quiescent phenotype of human myometrium in culture.

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Section: Discussioncontrasting

confidence: 85%

Section: Discussionmentioning

confidence: 58%

Modulation of Progesterone Receptor Isoform Expression in Pregnant Human Myometrium

Ilicic

Zakár

Paul

2017

BioMed Research International

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“…We postulate that the changes in intrauterine environment (endocrine changes, for example, progesterone[29]) and mechanical factors (e.g. stretching as gestation progresses [21, 30, 31]), among others can potentially contribute to activation of stress associated p38MAPK. This then promotes the aging of the fetal tissues, thus preparing them for delivery.…”

Section: Discussionmentioning

confidence: 99%

Differential senescence in feto-maternal tissues during mouse pregnancy

et al. 2016

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Background Human studies show that fetal membranes have a limited lifespan and undergo telomere-dependent cellular senescence that is augmented by oxidative stress and mediated by p38 mitogen activated protein kinase (MAPK). Further, these studies suggest that fetal membranes are anatomically physiologically positioned to transmit senescence signals that may initiate parturition at term. Methods Longitudinal evaluation of feto-maternal tissues from mouse pregnancies was undertaken to determine the molecular progression of senescence during normal pregnancy. On days 10–18 of gestation, C57BL/6 mice were euthanized. Fetal membranes, placenta, and decidua/uterus were collected. Tissues were examined for Telomere length (TL) and the presence of Phosphorylated (P) p38MAPK and p53, p21 and senescence associated β-Galactosidase (SA- β-Gal). Findings Telomere length negatively correlated with gestational age in fetal membranes (β= − 0.1901 ± 0.03125, p < 0.0001), placenta (−0.09000 ± 0.03474, p=0.0135), and decidua/uterus (− 0.1317 ± 0.03264, p=0.0003). Progressive activation p38MAPK was observed in all tissues from days 10 to day18, with the highest activation observed in fetal membranes. Activation of p53 was progressive in fetal membranes. In contrast, active p53 was constitutive in placenta and decidua/uterus throughout gestation. Detection of p21 indicated that pro-senescent change was higher in all compartments on day 18 as compared to other days. The number of SA-β-Gal positive cells increased in fetal membranes as gestation progressed. However, in placenta and uterus and decidua/uterus SA-β-Gal was seen only in days 15 and 18. Conclusions Telomere dependent p38 and p53 mediated senescence progressed in mouse fetal membranes as gestation advanced. Although senescence is evident, telomere dependent events were not dominant in placenta or decidua/uterus. Fetal membrane senescence may significantly contribute to mechanisms of parturition at term.

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“…However, an important study has revealed that women receiving 17-alpha-hydroxyl-progestrone-caproate prophylaxis before 27 weeks' gestation might have even an increased risk for preterm labor (34). Furthermore, it should be kept in mind that progesterone has no role in the prevention of preterm labor in twin pregnancy (35, 36) weekly injections of 17-alpha-hydroxyl-progestrone-caproate as well as vaginal progesterone suppositories can lead to a significant reduction in the rate of recurrent preterm labor among women who had treated with tocolytics to suppress the acute phase and also there is a considerable reduction in the neonatal complications. However, it seems that further future studies are needed to accurately define the mechanism of action of progesterone drugs in the prevention of preterm labor and to establish the optimal formulation, route of administration, dose, and gestational age at initiation.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Progesterone Therapy on the Gestation Length and Reduction of Neonatal Complications in Patients who had Received Tocolytic Therapy for Acute Phase of Preterm Labor

Lotfalizadeh¹,

Ghomian²,

Reyhani³

2013

Iran Red Crescent Med J

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BackgroundWhile tocolytic therapy can halt the process of delivery, some patients return before the 37th week of pregnancy with recurrence of preterm labor signs.ObjectivesThis study was designed to evaluate the efficacy of progesterone in the prolonging of gestation and reduction of neonatal complications.Material and MethodsIn a clinical trial in 2010, 110 singleton pregnant women admitted at Imam Reza Hospital, Mashhad, Iran, with the diagnosis of preterm labor were divided into three groups: 400 mg/d vaginal progesterone suppositories; 250 mg/w 17-alpha-hydroxyl-progestrone-caproate; and a control group with no additional treatment. After delivery, we assessed the duration between the first phases of labor to the recurrence of preterm labor. The neonatal complications, apgar score, birth weight, need for admission to NICU, and congenital malformations were compared between groups.ResultsThe mean gestational age was 34± 3 weeks in the first, 33.5 ± 3 weeks in the second and 32.5 ± 2 weeks in the control group. The duration of first phase of labor was 31 ± 17 days in the first, 36 ± 14 days in the second and 26 ± 22 days in the control group. The difference between study groups and the control group was significant (P < 0.005). The complications were lower in progesterone-receiving group in comparison to the control group.DiscussionThis study reveals that progesterone can significant reduce the rate of recurrent preterm labor and the several possible neonatal complications among women who had treated with tocolytics to suppress the acute phase.

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Uterine Stretch and Progesterone Action

Cited by 36 publications

References 44 publications

Modulation of Progesterone Receptor Isoform Expression in Pregnant Human Myometrium

Modulation of Progesterone Receptor Isoform Expression in Pregnant Human Myometrium

Differential senescence in feto-maternal tissues during mouse pregnancy

The Effects of Progesterone Therapy on the Gestation Length and Reduction of Neonatal Complications in Patients who had Received Tocolytic Therapy for Acute Phase of Preterm Labor

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