STK40 inhibits trophoblast fusion by mediating COP1 ubiquitination to degrade P57Kip2.

BACKGROUND: The syncytiotrophoblast (SCT) layer in the placenta serves as a crucial physical barrier separating maternal-fetal circulation, facilitating essential signal and substance exchange between the mother and fetus. Any abnormalities in its formation or function can result in various maternal syndromes, such as preeclampsia. The transition of proliferative villous cytotrophoblasts (VCT) from the mitotic cell cycle to the G0 phase is a prerequisite for VCT differentiation and their fusion into SCT. The imprinting gene P57Kip2, specifically expressed in intermediate VCT capable of fusion, plays a pivotal role in driving this key event. Moreover, aberrant expression of P57Kip2 has been linked to pathological placental conditions and adverse fetal outcomes. METHODS: Validation of STK40 interaction with P57Kip2 using rigid molecular simulation docking and co-immunoprecipitation. STK40 expression was modulated by lentivirus in BeWo cells, and the effect of STK40 on trophoblast fusion was assessed by real-time quantitative PCR, western blot, immunofluorescence, and cell viability and proliferation assays. Co-immunoprecipitation, transcriptome sequencing, and western blot were used to determine the potential mechanisms by which STK40 regulates P57Kip2. RESULTS: In this study, STK40 has been identified as a novel interacting protein with P57Kip2, and its expression is down-regulated during the fusion process of trophoblast cells. Overexpressing STK40 inhibited cell fusion in BeWo cells while stimulating mitotic cell cycle activity. Further experiments indicated that this effect is attributed to its specific binding to the CDK-binding and the Cyclin-binding domains of P57Kip2, mediating the E3 ubiquitin ligase COP1-mediated ubiquitination and degradation of P57Kip2. Moreover, abnormally high expression of STK40 might significantly contribute to the occurrence of preeclampsia. CONCLUSIONS: This study offers new insights into the role of STK40 in regulating the protein-level homeostasis of P57Kip2 during placental development.

Comparative influence of inappropriate gestational weight gain on pregnancy outcomes in IVF-conceived and spontaneously conceived twin pregnancies.

OBJECTIVE: To investigate the influence of inappropriate gestational weight gain (GWG) on pregnancy outcomes in twin pregnant women with in vitro fertilization (IVF) treatment. METHODS: This retrospective cohort study included 2992 twin pregnant women and categorized the participants as follows: (i) they were classified into spontaneous conception (SC) or IVF groups based on whether they received IVF treatment, and (ii) they were categorized into inadequate, optimal, or excessive GWG groups according to the International Organization for Migration Twin Pregnancy Guidelines. Initially, the study investigated the separate effects of IVF treatment and different levels of GWG on the outcomes of twin pregnancies. Subsequently, after adjusting for confounding factors, multifactorial logistic regression analysis was performed to further investigate the impact of IVF treatment and high GWG on twin pregnancy outcomes. Based on this, the analysis was stratified by whether IVF was used to explore the effects of different GWG levels on each subgroup (those who underwent IVF and those who conceived spontaneously). Finally, potential multiplicative interactions between IVF and different GWG categories were examined to identify their combined effect on pregnancy outcomes. RESULTS: The results showed that women with twin gestations conceived via IVF exhibited significantly higher maternal age, pre-pregnancy body mass index, and a greater incidence of GWG beyond recommended guidelines compared to the SC group. Furthermore, both IVF treatment and inappropriate GWG increased the risk of adverse pregnancy outcomes, respectively. Following adjustments for confounding variables through multifactorial logistic regression, it was demonstrated that both IVF treatment and high GWG significantly elevated the risk of adverse outcomes in twin pregnancies, such as admission to the neonatal intensive care unit. It is noteworthy that inappropriate GWG, combined with IVF treatment, will stepwise increase the incidence of intrahepatic cholestasis of pregnancy, respiratory failure, respiratory distress, pre-eclampsia, maternal intensive care unit admission, and postpartum hemorrhage risk. However, these outcomes were less affected by inappropriate GWG in the SC group. Lastly, this study did not unveil a significant interaction between the IVF procedure and disparate levels of GWG in relation to the adverse outcomes. CONCLUSION: A high incidence of inappropriate GWG in twin pregnancies with IVF treatment and inappropriate GWG conferred more adverse twin pregnancy outcomes in the IVF group relative to the SC group. This study indicates that proper management of GWG may be a breakthrough in reducing adverse outcomes in twin pregnancies associated with IVF. Therefore, implementing proactive interventions such as supervised exercise programs, prescribed physical or dietary plans, enhanced weight management, or personalized counseling, holds promise for lowering the risks associated with inappropriate GWG in twin pregnancies resulting from IVF.

Global research on emerging trends of obstetrics during the COVID-19 pandemic: A bibliometric analysis.

Coronavirus disease-2019 (COVID-19) has caused continuous effects on the global public, especially for susceptible and vulnerable populations like pregnant women. COVID-19-related studies and publications have shown blowout development, making it challenging to identify development trends and hot areas by using traditional review methods for such massive data. Aimed to perform a bibliometric analysis to explore the status and hotspots of COVID-19 in obstetrics. An online search was conducted in the Web of Science Core Collection (WOSCC) database from January 01, 2020 to November 31, 2022, using the following search expression: (((TS= ("COVID 19" OR "coronavirus 2019" OR "coronavirus disease 2019" OR "SARS-CoV-2" OR "2019-nCoV" OR "2019 novel coronavirus" OR "SARS coronavirus 2" OR "Severe Acute Respiratory Syndrome Coronavirus-2" OR "SARS-COV2")) AND TS= ("obstetric*" OR "pregnancy*" OR "pregnant" OR "parturition*" OR "puerperium"))). VOSviewer version 1.6.18, CiteSpace version 6.1.R6, R version 4.2.0, and Rstudio were used for the bibliometric and visualization analyses. 4144 articles were included in further analysis, including authors, titles, number of citations, countries, and author affiliations. The United States has contributed the most significant publications with the leading position. "Sahin, Dilek" has the largest output, and "Khalil, Asma" was the most influential author with the highest citations. Keywords of "Cov," "Experience," and "Neonate" with the highest frequency, and "Systematic Review" might be the new research hotspots and frontiers. The top 3 concerned genes included ACE2, CRP, and IL6. The new research hotspot is gradually shifting from the COVID-19 mechanism and its related clinical research to reviewing treatment options for pregnant women. This research uniquely delves into specific genes related to COVID-19's effects on obstetrics, a focus that has not been previously explored in other reviews. Our research enables clinicians and researchers to summarize the overall point of view of the existing literature and obtain more accurate conclusions.