Infertility has been a great challenge in reproductive medicine. At least 40% of human pregnancy losses are clinically unrecognized and occur because of embryo implantation failure. Identification of the proteins and biochemical factors involved in embryo implantation and that are essential for crosstalk between the embryo and uterus can further increase female fertility rates. The actin cytoskeleton and actin‐binding proteins (ABPs) are of great importance for cell morphology and rearrangement, which is crucial for trophoblast adhesion and invasion. However, the research on ABPs in embryo implantation is insufficient. In this report, we found that transgelin (TAGLN)2 is highly expressed in mouse blastocyst trophoblasts. Notably, inhibition of mouse blastocyst trophoblast TAGLN2 by lentivirus‐mediated RNA interference significantly impaired embryo adhesion and implantation ability. Further in vitro experiments demonstrated that TAGLN2 knockdown with small interfering RNA observably decreased the invasion and migration abilities of human trophoblast cells. Immunofluorescence colocalization and microscale thermophoresis analysis showed that TAGLN2 directly binds to actin. In addition, knockdown of TAGLN2 in trophoblast cells resulted in a remarkable reduction in F‐actin rather than G‐actin. Our findings reveal an unidentified role of TAGLN2 in regulation of trophoblast invasion and adhesion by promoting actin polymerization.—Liang, X., Jin, Y., Wang, H., Meng, X., Tan, Z., Huang, T., Fan, S. Transgelin 2 is required for embryo implantation by promoting actin polymerization. FASEB J. 33, 5667–5675 (2019). http://www.fasebj.org
Objective To describe our preliminary experience in the application of microwave ablation for selective fetal reduction in complicated monochorionic multiple pregnancies. Methods In this prospective study, 45 consecutive complicated monochorionic multiple pregnancies that underwent microwave ablation for selective fetal reduction from July 2015 to February 2017 were analyzed from the first case onward. All patients were managed at the Peking University Third Hospital in Beijing, China. Results There were 45 cases (twins in 40 and triplets in five) treated by microwave ablation. The median gestational age at surgery was 21.3 weeks (range, 15.9‐25.7 wk), with a mean total ablation time of 8.5 ± 4.2 (7.2‐9.7) minutes. There were 12 (26.7%) cases of postprocedural fetal loss. Thirty‐three women delivered alive at a median gestational age of 37.6 weeks (range, 28.6‐40.4 wk). There were no neonatal deaths in our cohort, and the overall survival rate was 73.3% (33/45). Preterm premature rupture of membranes occurred in 9 (20.0%) cases with a median of 7.0 weeks (range, 0.9‐16.3 wk) after the surgery. None of the surviving cotwins had evidence of thermal injury or neurological abnormalities. Conclusion Microwave ablation appears to be a safe and effective method for selective feticide in complicated monochorionic pregnancies.
Originally discovered in the circulation of pregnant women as a protein secreted by placental trophoblasts, the metalloprotease pregnancy-associated plasma protein A (PAPP-A) is also widely expressed by many other tissues. It cleaves insulin-like growth factor-binding proteins (IGFBPs) to increase the bioavailability of IGFs and plays essential roles in multiple growth-promoting processes. While the vast majority of the circulatory PAPP-A in pregnancy is proteolytically inactive due to covalent inhibition by proform of eosinophil major basic protein (proMBP), the activity of PAPP-A can also be covalently inhibited by another less characterized modulator, stanniocalcin-2 (STC2). However, the structural basis of PAPP-A proteolysis and the mechanistic differences between these two modulators are poorly understood. Here we present two cryo-EM structures of endogenous purified PAPP-A in complex with either proMBP or STC2. Both modulators form 2:2 heterotetramer with PAPP-A and establish extensive interactions with multiple domains of PAPP-A that are distal to the catalytic cleft. This exosite-binding property results in a steric hindrance to prevent the binding and cleavage of IGFBPs, while the IGFBP linker region-derived peptides harboring the cleavage sites are no longer sensitive to the modulator treatment. Functional investigation into proMBP-mediated PAPP-A regulation in selective intrauterine growth restriction (sIUGR) pregnancy elucidates that PAPP-A and proMBP collaboratively regulate extravillous trophoblast invasion and the consequent fetal growth. Collectively, our work reveals a novel covalent exosite-competitive inhibition mechanism of PAPP-A and its regulatory effect on placental function.
Objective To compare the outcomes of monochorionic triamniotic (MCTA) triplets managed expectantly with those reduced to twins. Method This was a retrospective cohort study comparing expectant management (EM) with fetal reduction (FR) to twins in 43 consecutive MCTA triplets with 3 live fetuses at 11–14 weeks between 2012 and 2021. Results Nineteen patients managed expectantly and 24 triplets reduced to twins were included. The rate of pregnancy with at least one survivor was 84.2% in the EM group and 66.7% in the FR group (P = 0.190). Compared to the EM cases, triplets reduced to twins had a higher median gestational age at delivery (36.0 vs. 33.3 weeks; P < 0.001), a higher mean birth weight (2244.3 ± 488.6 g vs. 1751.1 ± 383.2 g; P < 0.001) and a lower risk of preterm birth before 34 weeks (11.8% vs. 64.7%; P = 0.001). There were no significant differences in the risk of miscarriage, pregnancy complications and composite adverse neonatal outcomes. Conclusion In MCTA triplets, FR to twins could reduce the risk of preterm birth, whereas EM seems to be a reasonable choice when the priority is at least one survivor. However, due to the small sample size of this study, these findings must be interpreted with great caution.
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