CONTEXT: Preterm delivery is commonly caused by intraamniotic infection with expression of proinflammatory cytokines (IL-1beta) or by abruption resulting in generation of decidual thrombin. Although human parturition is not preceded by overt progesterone withdrawal, progesterone resistance likely leads to labor. The uteri of Hoxa10(-/-) mice demonstrate progesterone resistance; several genes, including prostaglandin receptors, are inappropriately regulated in response to progesterone. OBJECTIVE: We hypothesized that IL-1beta or thrombin would decrease HOXA10 expression, contributing to the progestin-resistant environment. We analyzed expression of HOX genes and their regulation by IL-1beta or thrombin in decidual cells. DESIGN AND SETTING: We conducted an in vitro experiment at an academic medical center. INTERVENTION: Term decidual cells were treated with estradiol (E(2)) or E(2) plus medroxyprogesterone acetate followed by addition of thrombin or IL-1beta. MAIN OUTCOME MEASURE: HOX mRNA was evaluated by microarray and confirmed by quantitative RT-PCR. Protein expression was detected using immunohistochemistry and Western analysis. RESULTS: HOXA9, HOXA10, and HOXA11 were expressed in decidual cells and regulated by IL-1beta and thrombin. HOXA10 was further analyzed because of its association with progesterone responsiveness. After E(2) treatment, IL-1beta and thrombin decreased HOXA10 mRNA by 94 and 81%, respectively. After E(2) plus medroxyprogesterone acetate treatment, IL-1beta and thrombin resulted in an 86 and 72% decrease in HOXA10 mRNA, respectively. A similar decrease was noted in HOXA10 protein expression. CONCLUSION: The expression of HOXA10 protein at term indicates that it may have a role in maintaining decidual cell phenotype and pregnancy. The dramatic decrease of HOXA10 in response to IL-1beta or thrombin may contribute to progestin resistance in preterm labor, mimicking progesterone resistance seen in Hoxa10(-/-) mice.
CONTEXT: Preterm delivery is commonly caused by intraamniotic infection with expression of proinflammatory cytokines (IL-1beta) or by abruption resulting in generation of decidual thrombin. Although human parturition is not preceded by overt progesterone withdrawal, progesterone resistance likely leads to labor. The uteri of Hoxa10(-/-) mice demonstrate progesterone resistance; several genes, including prostaglandin receptors, are inappropriately regulated in response to progesterone. OBJECTIVE: We hypothesized that IL-1beta or thrombin would decrease HOXA10 expression, contributing to the progestin-resistant environment. We analyzed expression of HOX genes and their regulation by IL-1beta or thrombin in decidual cells. DESIGN AND SETTING: We conducted an in vitro experiment at an academic medical center. INTERVENTION: Term decidual cells were treated with estradiol (E(2)) or E(2) plus medroxyprogesterone acetate followed by addition of thrombin or IL-1beta. MAIN OUTCOME MEASURE: HOX mRNA was evaluated by microarray and confirmed by quantitative RT-PCR. Protein expression was detected using immunohistochemistry and Western analysis. RESULTS:HOXA9, HOXA10, and HOXA11 were expressed in decidual cells and regulated by IL-1beta and thrombin. HOXA10 was further analyzed because of its association with progesterone responsiveness. After E(2) treatment, IL-1beta and thrombin decreased HOXA10 mRNA by 94 and 81%, respectively. After E(2) plus medroxyprogesterone acetate treatment, IL-1beta and thrombin resulted in an 86 and 72% decrease in HOXA10 mRNA, respectively. A similar decrease was noted in HOXA10 protein expression. CONCLUSION: The expression of HOXA10 protein at term indicates that it may have a role in maintaining decidual cell phenotype and pregnancy. The dramatic decrease of HOXA10 in response to IL-1beta or thrombin may contribute to progestin resistance in preterm labor, mimicking progesterone resistance seen in Hoxa10(-/-) mice.
Authors: Pooja Mittal; Roberto Romero; Adi L Tarca; Sorin Draghici; Chia-Ling Nhan-Chang; Tinnakorn Chaiworapongsa; John Hotra; Ricardo Gomez; Juan Pedro Kusanovic; Deug-Chan Lee; Chong Jai Kim; Sonia S Hassan Journal: Am J Obstet Gynecol Date: 2011-02 Impact factor: 8.661
Authors: Pooja Mittal; Roberto Romero; Adi L Tarca; Juan Gonzalez; Sorin Draghici; Yi Xu; Zhong Dong; Chia-Ling Nhan-Chang; Tinnakorn Chaiworapongsa; Stephen Lye; Juan Pedro Kusanovic; Leonard Lipovich; Shali Mazaki-Tovi; Sonia S Hassan; Sam Mesiano; Chong Jai Kim Journal: J Perinat Med Date: 2010-07-14 Impact factor: 1.901
Authors: Jie Yu; Sarah L Berga; Wei Zou; D Grace Yook; Joshua C Pan; Aurora Arroyo Andrade; Lijuan Zhao; Neil Sidell; Indrani C Bagchi; Milan K Bagchi; Robert N Taylor Journal: Endocrinology Date: 2017-12-01 Impact factor: 4.736
Authors: Alysson Zanatta; André M Rocha; Filomena M Carvalho; Ricardo M A Pereira; Hugh S Taylor; Eduardo L A Motta; Edmund C Baracat; Paulo C Serafini Journal: J Assist Reprod Genet Date: 2010-09-07 Impact factor: 3.412