Progesterone receptor isoform (A/B) ratio of human fetal membranes increases during term parturition

Oh, Soo‐Young; Kim, Chong Jai; Park, Insuk; Romero, Roberto; Sohn, Yoo-Kyung; Moon, Kyung Chul; Yoon, Bo Hyun

doi:10.1016/j.ajog.2005.05.071

Cited by 125 publications

(40 citation statements)

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“…1 However, the role of progesterone withdrawal, as measured by plasma progesterone concentration or the ratio of progesterone/estrogens, in the initiation of normal labor in humans or other primates is unclear. [2][3][4] Nevertheless, there is evidence that functional progesterone withdrawal caused by changes such as reduction in progesterone receptors 5 or relative increase in the progesterone receptor (PR)-A progesterone receptor isoform, which blocks PR-B isoform-mediated gene transcription 6 may trigger labor in humans. We are unaware of any study that has assessed the ability of measurement of salivary progesterone, which is representative of the biologically active unbound fraction in plasma or serum, 7 to predict preterm birth.…”

Section: Introductionmentioning

confidence: 99%

Salivary progesterone and estriol among pregnant women treated with 17-α-hydroxyprogesterone caproate or placebo

Klebanoff

Meis

Dombrowski

et al. 2008

American Journal of Obstetrics and Gynecology

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OBJECTIVE-The objectives of the study was to determine whether salivary progesterone (P) or estriol (E3) concentration at 16-20 weeks' gestation predicts preterm birth or the response to 17α-hydroxyprogesterone caproate (17OHPC) and whether 17OHPC treatment affected the trajectory of salivary P and E3 as pregnancy progressed.STUDY DESIGN-This was a secondary analysis of a clinical trial of 17OHPC to prevent preterm birth. Baseline saliva was assayed for P and E3. Weekly salivary samples were obtained from 40 women who received 17OHPC and 40 who received placebo in a multicenter ran-domized trial of 17OHPC to prevent recurrent preterm delivery.RESULTS-Both low and high baseline saliva P and E3 were associated with a slightly increased risk of preterm birth. However, 17OHPC prevented preterm birth comparably, regardless of baseline salivary hormone concentrations. 17OHPC did not alter the trajectory of salivary P over pregnancy, but it significantly blunted the rise in salivary E3 as well as the rise in the E3/P ratio. NIH Public AccessAuthor Manuscript Am J Obstet Gynecol. Author manuscript; available in PMC 2009 December 16. Published in final edited form as: Am J Obstet Gynecol. 2008 November ; 199(5): 506.e1-506.e7. doi:10.1016/j.ajog.2008.003. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript CONCLUSION-17OHPC flattened the trajectory of E3 in the second half of pregnancy, suggesting that the drug influences the fetoplacental unit. Keywords17-alpha-hydroxyprogesterone caproate; longitudinal studies; preterm birth; salivary estriol; salivary progesterone Progesterone has long been recognized as necessary for pregnancy maintenance, and the role of progesterone withdrawal in the initiation of labor in animal species has been known for decades. 1 However, the role of progesterone withdrawal, as measured by plasma progesterone concentration or the ratio of progesterone/estrogens, in the initiation of normal labor in humans or other primates is unclear. 2-4 Nevertheless, there is evidence that functional progesterone withdrawal caused by changes such as reduction in progesterone receptors 5 or relative increase in the progesterone receptor (PR)-A progesterone receptor isoform, which blocks PR-B isoform-mediated gene transcription 6 may trigger labor in humans. We are unaware of any study that has assessed the ability of measurement of salivary progesterone, which is representative of the biologically active unbound fraction in plasma or serum, 7 to predict preterm birth.In 2 recent randomized clinical trials, injections of 17-α-hydroxyprogesteronecaproate (17OHPC) 8 or vaginal suppositories containing progesterone 9 reduced the recurrence or occurrence of preterm birth among high-risk women. Because 17-α-hydroxyprogesterone is produced by the normal placenta in amounts greater than the doses administered in these clinical trials 10 and because normal plasma progesterone concentrations are 9 times higher than those of 17-α-hydroxyprogesterone 11 and greater than the dissociation c...

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Section: Introductionmentioning

confidence: 99%

Salivary progesterone and estriol among pregnant women treated with 17-α-hydroxyprogesterone caproate or placebo

Klebanoff

Meis

Dombrowski

et al. 2008

American Journal of Obstetrics and Gynecology

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“…5 Progesterone has a major role in pregnancy maintenance and its secretion has been demonstrated in the amnion, chorion and decidua in humans. 6,7 In the 1st trimester, progesterone is critical to pregnancy preservation until the placenta takes over this function. In later pregnancy, however, its function is less clear.…”

Section: Introductionmentioning

confidence: 99%

Membrane progesterone receptors in human regulatory T cells: a reality in pregnancy

Areia

Vale-Pereira

Alves

et al. 2015

BJOG

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Objective To provide evidence of the existence of membrane progesterone receptor alpha (mPRa) on regulatory T cells (Treg) in peripheral blood during pregnancy, postulating a possible explanation for the effect of progesterone on preterm birth.Design Cross-sectional study.Setting Tertiary Obstetric Department in a University Hospital.Population Healthy pregnant women.Methods Treg cells from peripheral blood samples were studied by flow cytometry using multiple monoclonal antibody expression. Conclusions This research shows that Treg cells express mPRa during pregnancy, which might play an important role in immune modulation by progesterone.

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“…PGR is regulated in utero in the fetal membranes with isoform expression for the two common forms progesterone receptor isoform A (PR-A) and progesterone receptor isoform B (PR-B) having reciprocally higher expression before and after labor (35). The PR-A form seems to behave as a repressor of PR-B in the amnion as well (36).…”

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confidence: 99%

Evaluation of Fetal and Maternal Genetic Variation in the Progesterone Receptor Gene for Contributions to Preterm Birth

et al. 2007

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Progesterone plays a critical role in the maintenance of pregnancy and has been effectively used to prevent recurrences of preterm labor. We investigated the role of genetic variation in the progesterone receptor (PGR) gene in modulating risks for preterm labor by examining both maternal and fetal effects. Cases were infants delivered prematurely at the University of Iowa. DNA was collected from the mother, infant, and father. Seventeen single nucleotide polymorphisms (SNP) and an insertion deletion variant in PGR were studied in 415 families. Results were then analyzed using transmission disequilibrium tests and log-linear-model-based analysis. DNA sequencing of the PGR gene was also carried out in 92 mothers of preterm infants. We identified significant associations between SNP in the PGR for both mother and preterm infant. No etiologic sequence variants were found in the coding sequence of the PGR gene. This study suggests that genetic variation in the PGR gene of either the mother or the fetus may trigger preterm labor. P reterm labor and preterm birth are major public health problems throughout the world. In the United States, preterm birth has been increasing in birth prevalence over the last two decades and now affects approximately 500,000 infants per year. Besides its association with mortality, there are both acute and chronic morbidities associated with the preterm birth, including long-term sequelae such as cognitive and motor delays. Genetic factors play a strong role in preterm birth (1). The best predictor for preterm delivery is the birth of a previous preterm infant to that woman (2-4). In addition, a family history of preterm delivery in the mother herself (5) or the mother's sister (6) strongly supports an underlying genetic component. In twin studies, the heritability of preterm delivery has been suggested to be approximately 40% (7). Progesterone, and in particular 17-␣ hydroxyprogesterone caproate (17p), has been shown to reduce the risk of a subsequent preterm delivery by approximately 30% in women who have had at least one preterm child (8 -14). Further, the earlier the gestational age of the first infant, the more effective progesterone is in prolonging the gestation of a subsequent pregnancy.While other mammals show a decrease in serum progesterone levels before parturition, no consistent evidence of this has been seen in humans. It has been suggested that changes in isoform ratio and/or the expression of the progesterone receptor may provide a "functional" progesterone withdrawal, leading to the initiation of labor (15)(16)(17)(18)(19)(20).Variation in the genes involved in progesterone synthesis or metabolism could be hypothesized as playing a role in preterm delivery as have single nucleotide polymorphisms (SNP) playing a role in inflammation, fetal membrane stability, immune response, sympathetic nerve action, angiogenesis, and clotting (21). In this report, we evaluated the role of genetic variation in the fetal and maternal progesterone receptor genes to identify women w...

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Progesterone receptor isoform (A/B) ratio of human fetal membranes increases during term parturition

Cited by 125 publications

References 16 publications

Salivary progesterone and estriol among pregnant women treated with 17-α-hydroxyprogesterone caproate or placebo

Salivary progesterone and estriol among pregnant women treated with 17-α-hydroxyprogesterone caproate or placebo

Membrane progesterone receptors in human regulatory T cells: a reality in pregnancy

Evaluation of Fetal and Maternal Genetic Variation in the Progesterone Receptor Gene for Contributions to Preterm Birth

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