Dataset Information

PTH-rP and PTH-R1 Expression in Placentas from Pregnancies Complicated by Gestational Diabetes: New Insights into the Pathophysiology of Hyperglycemia in Pregnancy.

ABSTRACT: this study investigated the expression of parathyroid hormone-related protein (PTH-rP) and PTH/PTH-rP receptor PTH-R1 in placentas from women with gestational DM (GDM), and the relationship between PTH-R1 and PTH-rP expression and pregnancy characteristics. we prospectively enrolled 78 pregnant women with GDM, and immunochemistry for PTH-rP and PTH-R1 was performed on placentas. Patients were grouped according to the positivity of PTH-R1 or PTH-rP expression, and pregnancy characteristics were compared between the two groups. PTH-rP and PTH-R1 expression were highest in the extravillous cytotrophoblast and in the decidua. In extravillous cytotrophoblast, PTH-rP expression was higher in women with abnormal at fasting glycemia compared to women with abnormal 60' or 120' glycemia (25/25, 50% vs. 6/28, 21.4%, χ2 = 6.12, p = 0.01), and PTH-R1 expression was higher in women with abnormal oral glucose tolerance test (OGTT) at fasting glycemia compared to women with abnormal 60' or 120' glycemia (37/50, 74% vs. 15/28, 53.6%, χ2 = 3.37, p = 0.06). In syncytiotrophoblast, PTH-rP-positive placentas were characterized by higher incidence of 1 min Apgar score < 7 (2/9, 22.2% vs. 2/69, 2.9%, χ2 = 6.11, p = 0.01) and maternal obesity (4/9, 44.4% vs. 11/69, 16.7%, χ2 = 3.81, p = 0.05). placental PTH-rP and PTH-R1 expression is dependent on the type of maternal hyperglycemia, and it is associated with adverse pregnancy outcomes.

SUBMITTER: Sirico A

PROVIDER: S-EPMC8394866 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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PTH-rP and PTH-R1 Expression in Placentas from Pregnancies Complicated by Gestational Diabetes: New Insights into the Pathophysiology of Hyperglycemia in Pregnancy.

Sirico Angelo A Dell'Aquila Marco M Tartaglione Linda L Moresi Sascia S Farì Giorgia G Pitocco Dario D Arena Vincenzo V Lanzone Antonio A

Diagnostics (Basel, Switzerland) 20210728 8

<h4>Background</h4>this study investigated the expression of parathyroid hormone-related protein (PTH-rP) and PTH/PTH-rP receptor PTH-R1 in placentas from women with gestational DM (GDM), and the relationship between PTH-R1 and PTH-rP expression and pregnancy characteristics.<h4>Methods</h4>we prospectively enrolled 78 pregnant women with GDM, and immunochemistry for PTH-rP and PTH-R1 was performed on placentas. Patients were grouped according to the positivity of PTH-R1 or PTH-rP expression, an ...[more]

PMID: 34441291

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Project description:BackgroundPrediction models have shown promise in helping clinicians and patients engage in shared decision-making by providing quantitative estimates of individual risk of important clinical outcomes. Gestational diabetes mellitus is a common complication of pregnancy, which places patients at higher risk of primary CD. Suspected fetal macrosomia diagnosed on prenatal ultrasound is a well-known risk factor for primary CD in patients with gestational diabetes mellitus, but tools incorporating multiple risk factors to provide more accurate CD risk are lacking. Such tools could help facilitate shared decision-making and risk reduction by identifying patients with both high and low chances of intrapartum primary CD.ObjectiveThis study aimed to develop and internally validate a multivariable model to estimate the risk of intrapartum primary CD in pregnancies complicated by gestational diabetes mellitus undergoing a trial of labor.Study designThis study identified a cohort of patients with gestational diabetes mellitus derived from a large, National Institutes of Health-funded medical record abstraction study who delivered singleton live-born infants at ≥34 weeks of gestation at a large tertiary care center between January 2002 and March 2013. The exclusion criteria included previous CD, contraindications to vaginal delivery, scheduled primary CD, and known fetal anomalies. Candidate predictors were clinical variables routinely available to a practitioner in the third trimester of pregnancy found to be associated with an increased risk of CD in gestational diabetes mellitus. Stepwise backward elimination was used to build the logistic regression model. The Hosmer-Lemeshow test was used to demonstrate goodness of fit. Model discrimination was evaluated via the concordance index and displayed as the area under the receiver operating characteristic curve. Internal model validation was performed with bootstrapping of the original dataset. Random resampling with replacement was performed for 1000 replications to assess predictive ability. An additional analysis was performed in which the population was stratified by parity to evaluate the model's predictive ability among nulliparous and multiparous individuals.ResultsOf the 3570 pregnancies meeting the study criteria, 987 (28%) had a primary CD. Of note, 8 variables were included in the final model, all significantly associated with CD. They included large for gestational age, polyhydramnios, older maternal age, early pregnancy body mass index, first hemoglobin A1C recorded in pregnancy, nulliparity, insulin treatment, and preeclampsia. Model calibration and discrimination were satisfactory with the Hosmer-Lemeshow test (P=.862) and an area under the receiver operating characteristic curve of 0.75 (95% confidence interval, 0.74-0.77). Internal validation demonstrated similar discriminatory ability. Stratification by parity demonstrated that the model worked well among both nulliparous and multiparous patients.ConclusionUsing information routinely available in the third trimester of pregnancy, a clinically pragmatic model can predict intrapartum primary CD risk with reasonable reliability in pregnancies complicated by gestational diabetes mellitus and may provide quantitative data to guide patients in understanding their individual primary CD risk based on preexisting and acquired risk factors.

Project description:Chorioamnionitis (CAM) is primarily a polymicrobial bacterial infection involving chorionic and amniotic membranes that is associated with increased risk of preterm delivery. Epoxyeicosatrienoic acids (EETs) are eicosanoids generated from arachidonic acid by cytochrome P450 enzymes and further metabolized mainly by soluble epoxide hydrolase (sEH) to produce dihydroxyeicosatrienoic acids (DHETs). As a consequence of this metabolism of EETs, sEH reportedly exacerbates several disease states; however, its role in CAM remains unclear. The objectives of this study were to (1) determine the localization of sEH and compare the changes it undergoes in the gestational tissues (placentas and fetal membranes) of women with normal-term pregnancies and those with pregnancies complicated by acute CAM; (2) study the effects of lipopolysaccharide (LPS) on the expression of sEH in the human gestational tissues; and (3) investigate the effect of 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a specific sEH inhibitor, on LPS-induced changes in 14,15-DHET and cytokines such as interleukin- (IL-) 1β and IL-6 in human gestational tissues in vitro and in pregnant mice. We found that women with pregnancies complicated by acute CAM had higher levels of sEH mRNA and protein in fetal membranes and villous tissues compared to those in women with normal-term pregnancies without CAM. Furthermore, fetal membrane and villous explants treated with LPS had higher tissue levels of sEH mRNA and protein and 14,15-DHET than those present in the vehicle controls, while the administration of AUDA in the media attenuated the LPS-induced production of 14,15-DHET in tissue homogenates and IL-1β and IL-6 in the media of explant cultures. Administration of AUDA also reduced the LPS-induced changes of 14,15-DHET, IL-1β, and IL-6 in the placentas of pregnant mice. Together, these results suggest that sEH participates in the inflammatory changes in human gestational tissues in pregnancies complicated by acute CAM.

Dataset Information

PTH-rP and PTH-R1 Expression in Placentas from Pregnancies Complicated by Gestational Diabetes: New Insights into the Pathophysiology of Hyperglycemia in Pregnancy.

Publications

PTH-rP and PTH-R1 Expression in Placentas from Pregnancies Complicated by Gestational Diabetes: New Insights into the Pathophysiology of Hyperglycemia in Pregnancy.

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