Rupture risk factors of fallopian tubal pregnancy

Zhang

et al. 2023

PeerJ

Objective To investigate whether the morphology, capillary number, and transcriptome expression profiles of ectopic pregnancy (EP) villi differ from those of normal pregnancy (NP) villi. Methods Hematoxylin-eosin (HE) and immunohistochemistry (IHC) staining for CD31 were conducted to compare differences in morphology and capillary number between EP and NP villi. Differentially expressed (DE) miRNAs and mRNAs were determined from transcriptome sequencing of both types of villi and used to construct a miRNA–mRNA network, from which hub genes were identified. Candidate DE-miRNAs and DE-mRNAs were validated by quantitative reverse transcription (qRT)-PCR. Correlations were identified between the number of capillaries and serum beta human chorionic gonadotropin (β-HCG) levels and between the expression levels of hub genes associated with angiogenesis and β-HCG levels. Results The mean and total cross-sectional areas of placental villi were significantly increased in EP compared with NP villi. Capillary density was greatly reduced in EP villi and was positively correlated with β-HCG levels. A total of 49 DE-miRNAs and 625 DE-mRNAs were identified from the sequencing data. An integrated analysis established a miRNA–mRNA network containing 32 DE-miRNAs and 103 DE-mRNAs. Based on the validation of hub mRNAs and miRNAs in the network, a regulatory pathway involving miR-491-5p–SLIT3 was discovered, which may have a role in the development of villous capillaries. Conclusion Villus morphology, capillary number, and miRNA/mRNA expression profiles in villous tissues were aberrant in EP placentas. Specifically, SLIT3, which is regulated by miR-491-5p, may contribute to the regulation of villous angiogenesis and was established as a putative predictor of chorionic villus development, providing a basis for future research.

Section: Discussionmentioning

confidence: 99%

Abnormal expression of SLIT3 induces intravillous vascularization dysplasia in ectopic pregnancy

Zhu

Zhang

et al. 2023

PeerJ

“…26 While REPs usually were defined high β-hCG level, active foetal hearts and maternal haemodynamic instability. 9 Exclusion criteria for all samples are IP with EP histories, miscarriage, preeclampsia, preterm delivery. Some risk factors associated with EP, for example, smoking, obvious tubal inflammatory adhesions, previous fallopian tubal diseases and tubal surgery histories, were also excluded for avoiding complications.…”

Section: Patient Samplesmentioning

confidence: 99%

“…7 By contrast, REP, the most common cause of maternal mortality among all tubal EPs, is commonly characterized by elevated β-hCG levels, an active foetal heart, and haemodynamic instability. 8,9 REPs thus require more invasive management, such as emergency laparoscopic resection of the fallopian tube and foetus. While the factors associated with increased risk of tubal rupture have been intensely investigated, such as maternal age (≥35), implantation in the isthmus and >5000 IU/L of β-hCG, 9,10 it remains uncertain whether these risk factors in REP are causal, due a lack of mechanistic understanding of the distinct events leading to AEP and REP. [11][12][13] The human placenta is a highly specialized and multifunctional organ that is essential for foetal growth and survival.…”

mentioning

confidence: 99%

“…8,9 REPs thus require more invasive management, such as emergency laparoscopic resection of the fallopian tube and foetus. While the factors associated with increased risk of tubal rupture have been intensely investigated, such as maternal age (≥35), implantation in the isthmus and >5000 IU/L of β-hCG, 9,10 it remains uncertain whether these risk factors in REP are causal, due a lack of mechanistic understanding of the distinct events leading to AEP and REP. [11][12][13] The human placenta is a highly specialized and multifunctional organ that is essential for foetal growth and survival. Three placentaspecific cell types are responsible for its primary functions, including villous cytotrophoblasts (vCTBs, the stem cell population in trophoblasts), syncytiotrophoblasts (STBs), and extravillous trophoblasts (EVTs).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Colony‐stimulating factor 1 positive (CSF1⁺) secretory epithelial cells induce excessive trophoblast invasion in tubal pregnancy rupture

et al. 2023

Cell Proliferation

Tubal ectopic pregnancy (TEP) occurs when an embryo aberrantly implants in the fallopian tube, leading to abortive or ruptured tubal ectopic pregnancy (AEP or REP). Poor outcomes of REP include maternal infertility or mortality. Current studies on the prevention and treatment of ruptured tubal ectopic pregnancy (REP) are unfortunately hampered by a lack of the cell spectrum and cell–cell communications in the maternal–foetal interface. Here, we investigate the mechanisms of tubal rupture through single‐cell transcriptome profiling of the fallopian tube‐trophoblast interface in REP, AEP and intrauterine pregnancy patients. In REP, extravillous trophoblast (EVTs) cells form a dominant cell population, displaying aggressive invasion and proliferation, with robust differentiation into three subsets. Cell communication analysis identified colony‐stimulating factor 1 (CSF1), overexpressed by fallopian tube secretory epithelial cells in REP, with CSF1R on EVTs and macrophages, as a ligand/receptor pair that stimulates EVT invasion and macrophage accumulation. CSF1+ secretory epithelial cells stimulate EVTs migration and invasion, leading to a tubal rupture in REP. These results provide a mechanistic context and cellular milieu leading to tubal rupture, facilitating further study and development of therapeutics for REP in early pregnancy.

“…In contrast, REPs are accompanied with high and continuously increasing hCG levels (>3000-5000 IU/L), active fetal hearts, and maternal hemodynamic instability. Several risk factors of EPs have been reported (Farquhar, 2005; Fukami et al, 2016; Hendriks et al, 2020; Marion and Meeks, 2012). However, whether these factors share a causal relationship with REP has not yet been substantiated, reflecting a lack of understanding regarding the mechanism(s) underlying the distinct pathologies of AEP and REP.…”

Section: Introductionmentioning

confidence: 99%

Trophoblast and blood vessel organoid cultures recapitulate the role of WNT2B in promoting intravillous vascularization in human intrauterine and ectopic pregnancy

Zhang

Luo

et al. 2022

Preprint

SummaryTubal ectopic pregnancy (TEP), a pregnancy complication caused by aberrant implantation in fallopian tubes, accounts for 9-13% pregnancy-related deaths. The lack of models for human TEP hampers the understanding of its pathological mechanisms. Here, we employed multiple models to investigate the crosstalk between human trophoblast development and intravillous vascularization. We found that the severity of TEP, the size of placental villi, and the depth of trophoblast invasion are correlated with the extent of intravillous vascularization. We identified a key pro-angiogenic factor secreted by trophoblasts, WNT2B, that promotes villous vasculogenesis, angiogenesis, and vascular network expansion. In an organoid coculture model consisting of trophoblast organoids and blood vessel organoids, knockdown of WNT2B in trophoblast organoids compromises their pro-angiogenic effect on the development of blood vessel organoids. These organoid-based models reveal an important role for WNT-mediated angiogenesis in pregnancies and could be employed to investigate the commutations between trophoblasts and endothelial/endothelial progenitor cells.