Progesterone Receptor Polymorphisms and Clinical Response to 17-α-hydroxyprogesterone Caproate

Manuck, Tracy A.; Lai, Yu-Ting; Meis, Paul J.; Dombrowski, Mitchell P.; Sibai, Baha M.; Spong, C. Y.; Rouse, D.; Durnwald, Celeste; Caritis, Steve N.; Wapner, R. J.; Mercer, Brian M.; Ramin, Susan M.

doi:10.1097/01.aoa.0000414104.72138.95

Cited by 8 publications

(8 citation statements)

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“…However, in a study testing for maternal and fetal effects of PR gene variation on preterm birth risk, suggestive maternal associations were identified for SNPs (single-nucleotide polymorphisms) in complete LD with PROGINS. Suggestive fetal associations with SNPs upstream of PR and not in LD with PROGINS were found and hint at the possibility of regulatory variation and alternate maternal and fetal mechanisms in PR mediated preterm birth risk (Ehn et al 2007) (for related studies in PR polymorphisms, see also Guoyang et al 2008;Manuck et al 2010aManuck et al ,b, 2011.…”

Section: Genetic Variation and Progesterone Receptor Functionmentioning

confidence: 96%

Genomics of Preterm Birth

Swaggart

Pavličev

Muglia

2015

Cold Spring Harbor Perspectives in Medicine

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The molecular mechanisms controlling human birth timing at term, or resulting in preterm birth, have been the focus of considerable investigation, but limited insights have been gained over the past 50 years. In part, these processes have remained elusive because of divergence in reproductive strategies and physiology shown by model organisms, making extrapolation to humans uncertain. Here, we summarize the evolution of progesterone signaling and variation in pregnancy maintenance and termination. We use this comparative physiology to support the hypothesis that selective pressure on genomic loci involved in the timing of parturition have shaped human birth timing, and that these loci can be identified with comparative genomic strategies. Previous limitations imposed by divergence of mechanisms provide an important new opportunity to elucidate fundamental pathways of parturition control through increasing availability of sequenced genomes and associated reproductive physiology characteristics across diverse organisms.

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Section: Genetic Variation and Progesterone Receptor Functionmentioning

confidence: 96%

Genomics of Preterm Birth

Swaggart

Pavličev

Muglia

2015

Cold Spring Harbor Perspectives in Medicine

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“…Progesterone is a key hormonal regulator of the female reproductive system and plays a major role in preparing the uterus for implantation and in the establishment and maintenance of pregnancy (32,33). PTB in women is associated with changes in circulating hormones such as progesterone deficits (34)(35)(36)(37)(38) or with inadequate responses to progesterone (32,39). To further demonstrate the effectiveness of bitter tastants in preventing PTB, we established another mouse model of preterm labor with the progesterone receptor antagonist RU-486.…”

Section: Bitter Tastant Chq Protects Against Mouse Ptbs Better Than Cmentioning

confidence: 99%

Bitter taste receptors as targets for tocolytics in preterm labor therapy

et al. 2017

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Preterm birth (PTB) is the leading cause of neonatal mortality and morbidity, with few prevention and treatment options. Uterine contraction is a central feature of PTB, so gaining new insights into the mechanisms of this contraction and consequently identifying novel targets for tocolytics are essential for more successful management of PTB. Here we report that myometrial cells from human and mouse express bitter taste receptors (TAS2Rs) and their canonical signaling components ( G-protein gustducin and phospholipase C β2). Bitter tastants can completely relax myometrium precontracted by different uterotonics. In isolated single mouse myometrial cells, a phenotypical bitter tastant (chloroquine, ChQ) reverses the rise in intracellular Ca concentration ([Ca]) and cell shortening induced by uterotonics, and this reversal effect is inhibited by pertussis toxin and by genetic deletion of α-gustducin. In human myometrial cells, knockdown of TAS2R14 but not TAS2R10 inhibits ChQ's reversal effect on an oxytocin-induced rise in [Ca] Finally, ChQ prevents mouse PTBs induced by bacterial endotoxin LPS or progesterone receptor antagonist mifepristone more often than current commonly used tocolytics, and this prevention is largely lost in α-gustducin-knockout mice. Collectively, our results reveal that activation of the canonical TAS2R signaling system in myometrial cells produces profound relaxation of myometrium precontracted by a broad spectrum of contractile agonists, and that targeting TAS2Rs is an attractive approach to developing effective tocolytics for PTB management.-Zheng, K., Lu, P., Delpapa, E., Bellve, K., Deng, R., Condon, J. C., Fogarty, K., Lifshitz, L. M., Simas, T. A. M., Shi, F., ZhuGe, R. Bitter taste receptors as targets for tocolytics in preterm labor therapy.

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“…Genetik polimorfizm (örneğin; 7. kromozom), bu artışta rol oynuyor olabilir. 64,65 Doğuştan bağışıklık sisteminden sorumlu genlerde polimorfizmi olan anneler ve fetüslerde spontan preterm doğum ve PPROM riski artmaktadır.…”

Section: Geneti̇k Faktörlerunclassified