Advanced Research in Early Pregnancy Loss

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 4658

Special Issue Editors


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Guest Editor
Sichuan University Joint Laboratory for Reproductive Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong
Interests: reproductive medicine (endometriosis, miscarriage, implantation failure, polycystic ovary syndrome); developmental biology (redox control, gene dosage); maternal medicine (preeclampsia, gestational diabetes mellitus); fetal medicine (fetal hypoxia, preterm, fetal growth restriction)
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Guest Editor
Department of Obstetrics & Gynecology, The Chinese University of Hong Kong, Hong Kong, China
Interests: recurrent pregnancy loss; implantation failure; endometrial receptivity

Special Issue Information

Dear Colleagues,

Early human pregnancy is a complex procedure involving a series of maternal endocrinological, metabolic, immunological, hematological, cellular and molecular adaptions that are critical to establish a dynamical homeostatic environment for embryo implantation, decidualization, placentation and fetal development. Accumulated evidence has shown that the disruption of this delicately modulated homeostasis will cause implantation failure, insufficient decidualization, and defective placentation. Clinical presentations include implantation failure and spontaneous miscarriage, which mostly occur in the first trimester of gestation, and are generally referred to as pregnancy loss. Almost half of the cases of pregnancy loss cannot be explained. Furthermore, it can occur consecutively, i.e., recurrent implantation failure and miscarriage. Thanks to the rapid development and application of biomedicines, omics and molecular techniques,  new and exciting findings have been emerging to unveil the underlying mechanism of pregnancy loss, especially in terms of maternal adaptions and maternal-fetal interactions. How these scientific discoveries could be translated into clinical application and practice has further attracted the interest of clinicians, caretakers, scientists, pharmaceutical companies, health care policy makers, patients and their families for potential improvements in diagnosis, monitoring, and treatment, and the prediction of better pregnancy outcomes. This Special Issue will focus on the advances and updates in the research of early pregnancy loss, including the underlying mechanisms, from signaling pathways and cellular functions, to animal studies and translational studies with potential clinical applications.

Prof. Dr. Chi Chiu Wang
Prof. Dr. Tao Zhang
Guest Editors

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Keywords

  • pregnancy loss
  • miscarriage
  • implantation failure
  • mechanism
  • endocrinology
  • metabolism
  • immunology

Published Papers (2 papers)

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18 pages, 4021 KiB  
Article
Designing Effective Multi-Target Drugs and Identifying Biomarkers in Recurrent Pregnancy Loss (RPL) Using In Vivo, In Vitro, and In Silico Approaches
by Andrés Alexis Ramírez-Coronel, Amirabbas Rostami, Laith A. Younus, José Luis Arias Gonzáles, Methaq Hadi Lafta, Ali H. Amin, Mohammed Abdulkadhim Saadoon, Hayder Mahmood Salman, Abolfazl Bahrami, Rossa Feilei and Reza Akhavan-Sigari
Biomedicines 2023, 11(3), 879; https://doi.org/10.3390/biomedicines11030879 - 13 Mar 2023
Viewed by 2346
Abstract
Recurrent pregnancy loss (RPL) occurs in approximately 5% of women. Despite an abundance of evidence, the molecular mechanism of RPL’s pathology remains unclear. Here, we report the protective role of polo-like kinase 1 (PLK1) during RPL. We aimed to construct an RPL network [...] Read more.
Recurrent pregnancy loss (RPL) occurs in approximately 5% of women. Despite an abundance of evidence, the molecular mechanism of RPL’s pathology remains unclear. Here, we report the protective role of polo-like kinase 1 (PLK1) during RPL. We aimed to construct an RPL network utilizing GEO datasets and identified hub high-traffic genes. We also investigated whether the expressions of PLK1 were altered in the chorionic villi collected from women with RPL compared to those from healthy early pregnant women. Gene expression differences were evaluated using both pathway and gene ontology (GO) analyses. The identified genes were validated using in vivo and in vitro models. Mice with PLK1-overexpression and PLK1-knockdown in vitro models were produced by transfecting certain plasmids and si-RNA, respectively. The apoptosis in the chorionic villi, mitochondrial function, and NF-κB signaling activity was evaluated. To suppress the activation of PLK1, the PLK1 inhibitor BI2536 was administered. The HTR-8/SVneo and JEG-3 cell lines were chosen to establish an RPL model in vitro. The NF-κB signaling, Foxo signaling, PI3K/AKT, and endometrial cancer signaling pathways were identified via the RPL regulatory network. The following genes were identified: PLK1 as hub high-traffic gene and MMP2, MMP9, BAX, MFN1, MFN2, FOXO1, OPA1, COX15, BCL2, DRP1, FIS1, TRAF2, and TOP2A. Clinical samples were examined, and the results demonstrated that RPL patients had tissues with decreased PLK1 expression in comparison to women with normal pregnancies (p < 0.01). In vitro, PLK1 knockdown induced the NF-κB signaling pathway and apoptosis activation while decreasing cell invasion, migration, and proliferation (p < 0.05). Furthermore, the in vivo model proved that cell mitochondrial function and chorionic villi development are both hampered by PLK1 suppression. Our findings revealed that the PLK1/TRAF2/NF-κB axis plays a crucial role in RPL-induced chorionic villi dysfunction by regulating mitochondrial dynamics and apoptosis and might be a potential therapeutic target in the clinic. Full article
(This article belongs to the Special Issue Advanced Research in Early Pregnancy Loss)
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13 pages, 619 KiB  
Article
Genetic Polymorphisms in the 3′-Untranslated Regions of SMAD5, FN3KRP, and RUNX-1 Are Associated with Recurrent Pregnancy Loss
by Min-Jung Kwon, Ji-Hyang Kim, Jeong-Yong Lee, Eun-Ju Ko, Hyeon-Woo Park, Ji-Eun Shin, Eun-Hee Ahn and Nam-Keun Kim
Biomedicines 2022, 10(7), 1481; https://doi.org/10.3390/biomedicines10071481 - 22 Jun 2022
Cited by 2 | Viewed by 1744
Abstract
Recurrent pregnancy loss (RPL) is typically defined as two or more consecutive pregnancy losses prior to 20 weeks of gestation. Although the causes of idiopathic RPL are not completely understood, vascular development and glucose concentration were reported to correlate with the pregnancy loss. [...] Read more.
Recurrent pregnancy loss (RPL) is typically defined as two or more consecutive pregnancy losses prior to 20 weeks of gestation. Although the causes of idiopathic RPL are not completely understood, vascular development and glucose concentration were reported to correlate with the pregnancy loss. The TGF-β signaling pathway which plays a significant role in pregnancy is activated by the interaction between high glucose and SMAD signaling and affects the vascular cells. SMAD5 and RUNX-1 are involved in the TGF-β signaling pathway and contribute to advanced glycation end products (AGEs) production and vascular development. FN3KRP, a newly described gene, is also associated with vascular diseases and suggested to relate to AGEs. Therefore, in the present study, we investigated associations between RPL risk and genetic polymorphisms of SMAD5, FN3KRP, and RUNX-1 in 388 women with RPL and 280 healthy control women of Korean ethnicity. Participants were genotyped using real-time polymerase chain reaction and restriction fragment length polymorphism assay to determine the frequency of SMAD5 rs10515478 C>G, FN3KRP rs1046875 G>A, and RUNX-1 rs15285 G>A polymorphisms. We found that women with RPL had lower likelihoods of the FN3KRP rs1046875 AA genotype (adjusted odds ratio (AOR), 0.553; p = 0.010) and recessive model (AOR, 0.631; p = 0.017). Furthermore, combination analysis showed that SMAD5 rs10515478 C>G and FN3KRP rs1046875 G>A mutant alleles were together associated with reduced RPL risk. These findings suggest that the FN3KRP rs1046875 G>A polymorphism has a significant role on the prevalence of RPL in Korean women. Considering that it is the first study indicating a significant association between FN3KRP and pregnancy disease, RPL, our results suggest the need for further investigation of the role of FN3KRP in pregnancy loss. Full article
(This article belongs to the Special Issue Advanced Research in Early Pregnancy Loss)
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