Progesterone receptor membrane components: key regulators of fetal membrane integrity.

Pro-pregnancy hormone progesterone (P4) helps to maintain a quiescent status of uterine tissues during gestation. However, P4's functional role in maintaining fetal membrane (amniochorion) integrity remains unclear. P4 functions through its membrane receptors (progesterone receptor membrane components (PGRMCs)) as fetal membrane cells lack nuclear receptors. This study screened the differential expression of PGRMCs in the fetal membranes and tested P4-PGRMC interactions under normal and oxidative stress (OS) conditions expected that can disrupt P4-PGRMC interactions impacting fetal membrane stability resulting in parturition. Human fetal membranes were collected from term and preterm deliveries (N = 5). Immunohistochemistry and western blot localized and determined differential expression of P4 receptors. Primary amnion epithelial, mesenchymal (AMCs), and chorion cell were treated with P4 alone or co-treated (P4 + OS induced by cigarette smoke extract (CSE)). Proximity ligation assay (PLA) documented P4-receptor binding, whereas P4 enzyme-linked immunosorbent assay documented culture supernatant levels. Immunohistology confirmed lack of nuclear progesterone receptors; however, confirmed expressions of PGRMC 1 and 2. Term labor (P = 0.01) and preterm rupture (P = 0.01) are associated with significant downregulation of PGRMC2. OS-induced differential downregulation of PGRMCs in both amnion and chorion cells (all P < 0.05) and downregulates P4 release (AMCs; P = 0.01). The PLA showed preferential receptor-ligand binding in amnion and chorion cells. Co-treatment of P4 + CSE did not reverse CSE-induced effects. In conclusion, P4-PGRMCs interaction maintains fetal membranes' functional integrity throughout pregnancy. Increased OS reduces endogenous P4 production and cell type-dependent downregulation of PGRMCs. These changes can lead to fetal membrane-specific "functional progesterone withdrawal," contributing to the dysfunctional fetal membrane status seen at term and preterm conditions.

Effects of medication intake in early pregnancy on the fetal fraction of cell-free DNA testing.

OBJECTIVES: To determine the association between medications intake in early pregnancy and variation in the fetal fraction (FF) in pregnant women undergoing cell-free DNA (cfDNA) testing. METHODS: We performed a retrospective cohort study of women (n = 1051) undergoing cfDNA testing at an academic center. The exposed group included women taking medications (n = 400; 38.1%), while the nonexposed group consisted of women taking no medications (n = 651; 61.9%). Our primary outcome was FF. We performed univariate and multivariate analyses as appropriate. RESULTS: The FFs were 8.8% (6.6-12.1), 8.7% (6.3-11.6), and 7.7% (5.1-9.3) among women taking 0, 1, and two or more medications, respectively (P < 0.01). Using multivariable linear mixed effects model, the mean FF was significantly lower among those taking two or more medications compared with the nonexposed group. FF was directly correlated with gestational age at the time of cfDNA testing and inversely correlated with maternal obesity. Exposure to metformin was associated with 1.8% (0.2-3.4) lower mean FF when compared with the nonexposed group (P = 0.02). Obesity and intake of two or more medications were associated with higher hazard ratio of having a low FF less than 4%. CONCLUSIONS: Exposure to metformin or two or more medications was associated with decreased FF, and obesity is associated with delay in achieving adequate FF percentage. These findings should be considered while counseling patients on test limitations.

Peripartum Abdominal Compartment Syndrome Following Extracorporeal Hemodynamic Support.

In massive pulmonary embolism (PE), anticoagulation and thrombolytics may increase the risk of retroperitoneal bleeding following vascular cannulation for extracorporeal hemodynamic support resulting in abdominal compartment syndrome (ACS). A 27-year-old women at 33 weeks of gestation presented with acute chest pain and shortness of breath. Massive PE was diagnosed. Intravenous unfractionated heparin was started together with catheter-directed tissue plasminogen activator (tPA) infusion and mechanical thrombectomy. During the procedure, cardiac arrest developed. Cardiopulmonary resuscitation, intravenous tPA, and urgent perimortem cesarean delivery were performed. After return of spontaneous circulation, profound right ventricular failure required venoarterial membrane oxygenation. Six hours afterward, ACS secondary to retroperitoneal bleeding developed, requiring surgical intervention. ACS may result from retroperitoneal bleeding following cannulation for extracorporeal hemodynamic support.