Possible Association between Cathepsin V and the Development of Placenta Accreta Spectrum Disorders

Matsukawa, Satoshi; Sato, Seiji; Kotani, Tomomi; Wang, Jingwen; Miki, Rika; Moriyama, Yoshinori; Nakano, Tomoko; Mano, Yukio; Tsuda, Hiroyuki; Koji, Takehiko; Kikkawa, Fumitaka

doi:10.1159/000496609

Cited by 4 publications

(4 citation statements)

References 35 publications

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“…The placenta is a complex, temporary organ composed of two parts: the maternal decidua and the fetal trophoblast [1,2]. PAS is a condition in which the placenta attaches and invades the myometrium, instead of the normal decidualized endometrium, beyond the physiological level of Nitabuch's layer [2,4,6,7].…”

Section: Introductionmentioning

confidence: 99%

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Biomolecules Involved in Both Metastasis and Placenta Accreta Spectrum—Does the Common Pathophysiological Pathway Exist?

Rekowska,

Obuchowska,

Bartosik

et al. 2023

Cancers

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The process of epithelial-to-mesenchymal transition (EMT) is crucial in the implantation of the blastocyst and subsequent placental development. The trophoblast, consisting of villous and extravillous zones, plays different roles in these processes. Pathological states, such as placenta accreta spectrum (PAS), can arise due to dysfunction of the trophoblast or defective decidualization, leading to maternal and fetal morbidity and mortality. Studies have drawn parallels between placentation and carcinogenesis, with both processes involving EMT and the establishment of a microenvironment that facilitates invasion and infiltration. This article presents a review of molecular biomarkers involved in both the microenvironment of tumors and placental cells, including placental growth factor (PlGF), vascular endothelial growth factor (VEGF), E-cadherin (CDH1), laminin γ2 (LAMC2), the zinc finger E-box-binding homeobox (ZEB) proteins, αVβ3 integrin, transforming growth factor β (TGF-β), β-catenin, cofilin-1 (CFL-1), and interleukin-35 (IL-35). Understanding the similarities and differences in these processes may provide insights into the development of therapeutic options for both PAS and metastatic cancer.

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Section: Introductionmentioning

confidence: 99%

“…Over the past five decades, PAS has emerged as one of the most significant obstetric complications, leading to peripartum hemorrhage, organ failure, and disseminated intravascular coagulation (DIC). These result in increased maternal and fetal morbidity and mortality [4,7].…”

Section: Introductionmentioning

confidence: 99%

Biomolecules Involved in Both Metastasis and Placenta Accreta Spectrum—Does the Common Pathophysiological Pathway Exist?

Rekowska,

Obuchowska,

Bartosik

et al. 2023

Cancers

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show abstract

“…The ovulation rate is an important determinant of litter size, while the uterus is critical for embryo implantation ( 15 , 40 , 41 ). Furthermore, CTSS expression underlies hormonal regulation in maternal tissues, is supportive of embryo implantation and is highly expressed in embryonic trophectoderm apposition sites and non-apposition sites ( 42 , 43 ). Therefore, the upregulation of CTSS expression in the uterus of multilamb ewes improves lambing numbers in goats by affecting late embryo attachment.…”

Section: Discussionmentioning

confidence: 99%

Effect of CTSS non-synonymous mutations on litter size in Qianbei Ma goats

Zhang,

Chen,

Ruan

et al. 2023

Front. Vet. Sci.

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Cathepsin S (CTSS) is a member of the cysteine protease family closely related to reproductive regulation in goats. However, its effect on litter size in goats remains unclear. In this study, the relationship between CTSS gene polymorphisms and litter size was revealed by analyzing the DNA sequence and mRNA expression of CTSS in the gonadal axis of Qianbei Ma goats. In addition, bioinformatics methods were used to evaluate the effect of non-synonymous mutations on CTSS protein structure and function. CTSS was expressed in all parts of the gonadal axis of Qianbei Ma goats, with the highest expression in the uterus in the multi-lamb group and in the fallopian tube in the single-lamb group. The sequencing results showed that four SNPs in CTSS, including g.7413C → T, g.8816A → T, g.9191 T → G and g.10193G → A, were significantly correlated with litter size (p < 0.05). All four analyzed mutation sites were in strong linkage disequilibrium (r2 > 0.33, D′ > 0.70). Additionally, the haplotype Hap1/2 had a significantly higher frequency than the other haplotypes (p < 0.05). g.7413C → T and g.8816A → T were non-synonymous mutations. The g.7413C → T mutation resulted in the substitution of serine 161 of the CTSS protein with phenylalanine (p.S161F), and the g.8816A → T mutation resulted in the substitution of aspartate 219 with tyrosine (p.N219Y). p.S161F was highly conserved across 13 species and that p.N219Y was relatively conserved in cloven-hoofed species. Mutations at two sites changed the local conformation of the CTSS protein, reduced its stability, and affected its function and goat breed evolution. These findings confirm that CTSS affects the lambing traits of goats and provide a theoretical basis for the regulatory mechanism of CTSS in affecting litter size.

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“…Excessive invasion of extravillous trophoblasts (EVTs) is essential in the development of PAS. At this point, EVTs have a strong ability of proliferation and migration ( Matsukawa et al, 2019 ). The functions and pathways related to cell proliferation and migration (cell adhesion) were enriched in all functional enrichment analyses in this study.…”

Section: Discussionmentioning

confidence: 99%

Systematic Identification of Hub Genes in Placenta Accreta Spectrum Based on Integrated Transcriptomic and Proteomic Analysis

et al. 2020

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Placenta accreta spectrum (PAS) is a pathological condition of the placenta with abnormal adhesion or invasion of the placental villi to the uterine wall, which is associated with a variety of adverse maternal and fetal outcomes. Although some PAS-related molecules have been reported, the underlying regulatory mechanism is still unclear. Compared with the study of single gene or pathway, omics study, using advanced sequencing technology and bioinformatics methods, can increase our systematic understanding of diseases. In this study, placenta tissues from 5 patients with PAS and 5 healthy pregnant women were collected for transcriptomic and proteomic sequencing and integrated analysis. A total of 728 messenger RNAs and 439 proteins were found to be significantly different between PAS group and non-PAS group, in which 23 hub genes were differentially expressed in both transcriptome and proteome. Functional enrichment analysis showed that the differentially expressed genes were mainly related to cell proliferation, migration and vascular development. Totally 18 long non-coding RNA were found that might regulate the expression of hub genes. Many kinds of single nucleotide polymorphism, alternative splicing and gene fusion of hub genes were detected. This is the first time to systematically explore the hub genes and gene structure variations of PAS through integrated omics analysis, which provided a genetic basis for further in-depth study on the underlying regulatory mechanism of PAS.

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Possible Association between Cathepsin V and the Development of Placenta Accreta Spectrum Disorders

Cited by 4 publications

References 35 publications

Biomolecules Involved in Both Metastasis and Placenta Accreta Spectrum—Does the Common Pathophysiological Pathway Exist?

Biomolecules Involved in Both Metastasis and Placenta Accreta Spectrum—Does the Common Pathophysiological Pathway Exist?

Effect of CTSS non-synonymous mutations on litter size in Qianbei Ma goats

Systematic Identification of Hub Genes in Placenta Accreta Spectrum Based on Integrated Transcriptomic and Proteomic Analysis

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