FPR2 serves a role in recurrent spontaneous abortion by regulating trophoblast function via the PI3K/AKT signaling pathway

Li, Anna; Li, Shuxian; Zhang, Chongyu; Fang, Zhenya; Sun, Yaqiong; Peng, Yanjie; Wang, Xietong; Zhang, Meihua

doi:10.3892/mmr.2021.12478

Cited by 11 publications

(2 citation statements)

References 48 publications

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“…Activated AKT plays a key role in cellular processes involved in cell survival, growth, and proliferation [ 58 ]. Although AKT functions may vary depending on the cell and tissue context [ 59 ], phosphorylated AKT may be involved in placental homeostasis, as it is well known that activated AKT regulates trophoblast cell function [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Vertical Intrauterine Bovine and Ovine Papillomavirus Coinfection in Pregnant Cows

De Falco,

Cutarelli,

Leonardi

et al. 2024

Pathogens

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There is very little information available about transplacental infections by the papillomavirus in ruminants. However, recent evidence has emerged of the first report of vertical infections of bovine papillomavirus (BPV) in fetuses from naturally infected, pregnant cows. This study reports the coinfection of BPV and ovine papillomavirus (OaPV) in bovine fetuses from infected pregnant cows suffering from bladder tumors caused by simultaneous, persistent viral infections. Some molecular mechanisms involving the binary complex composed of Eras and platelet-derived growth factor β receptor (PDGFβR), by which BPVs and OaPVs contribute to reproductive disorders, have been investigated. A droplet digital polymerase chain reaction (ddPCR) was used to detect and quantify the nucleic acids of the BPVs of the Deltapapillomavirus genus (BPV1, BPV2, BPV13, and BPV14) and OaPVs belonging to the Deltapapillomavirus (OaPV1, OaPV2, and OaPV4) and Dyokappapapillomavirus (OaPV3) genera in the placenta and fetal organs (heart, lung, liver, and kidneys) of four bovine fetuses from four pregnant cows with neoplasia of the urinary bladder. A papillomaviral evaluation was also performed on the bladder tumors and peripheral blood of these pregnant cows. In all fetal and maternal samples, the genotype distribution of BPVs and OaPVs were evaluated using both their DNA and RNA. A BPV and OaPV coinfection was seen in bladder tumors, whereas only BPV infection was found in peripheral blood. The genotype distribution of both the BPVs and OaPVs detected in placentas and fetal organs indicated a stronger concordance with the viral genotypes detected in bladder tumors rather than in peripheral blood. This suggests that the viruses found in placentas and fetuses may have originated from infected bladders. Our study highlights the likelihood of vertical infections with BPVs and OaPVs and emphasizes the importance of gaining further insights into the mechanisms and consequences of this exposure. This study warrants further research as adverse pregnancy outcomes are a major source of economic losses in cattle breeding.

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Section: Discussionmentioning

confidence: 99%

Vertical Intrauterine Bovine and Ovine Papillomavirus Coinfection in Pregnant Cows

De Falco,

Cutarelli,

Leonardi

et al. 2024

Pathogens

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“…FPR2 has been found to trigger trophoblast dysfunction through the PI3K/AKT signalling pathway, leading to recurrent spontaneous abortions [ 50 ]. The PI3K/Akt signalling pathway affects embryo implantation by regulating the expression of RhoA [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of N Acetylcysteine on the Expression of Genes Associated with Reproductive Performance in the Goat Uterus during Early Gestation

Chen

Guo

et al. 2022

Animals

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N acetylcysteine (NAC) affects antioxidation and reactive oxygen species scavenging in the body and thereby promotes embryonic development and implantation and inhibits inflammation. The mechanism through which NAC regulates reproductive performance in the uteri of goats during early gestation remains unclear. In this study, the treatment group was fed 0.07% NAC for the first 35 days of gestation, whereas the control group received no NAC supplementation. The regulatory genes and key pathways associated with goat reproductive performance under NAC supplementation were identified by RNA-seq. RT–qPCR was used to verify the sequencing results and subsequently construct tissue expression profiles of the relevant genes. RNA-seq identified 19,796 genes coexpressed in the control and treatment groups and 1318 differentially expressed genes (DEGs), including 787 and 531 DEGs enriched in the treatment and control groups, respectively. A GO analysis revealed that the identified genes mapped to pathways such as cell activation, cytokine production, cell mitotic processes, and angiogenesis, and a KEGG enrichment analysis showed that the DEGs were enriched in pathways associated with reproductive regulation, immune regulation, resistance to oxidative stress, and cell adhesion. The RT–qPCR analysis showed that BDNF and CSF-1 were most highly expressed in the uterus, that WIF1 and ESR2 showed low expression in the uterus, and that CTSS, PTX3, and TGFβ-3 were most highly expressed in the oviduct, which indicated that these genes may be directly or indirectly involved in the modulation of reproduction in early-gestation goats. These findings provide fundamental data for the NAC-mediated modulation of the reproductive performance of goats during early gestation.

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Quercetin promotes the proliferation, migration, and invasion of trophoblast cells by regulating the miR‐149‐3p/AKT1 axis

Wang,

Zhao,

et al. 2024

The Kaohsiung J of Med Scie

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Recurrent spontaneous abortion (RSA) has a complex pathogenesis with an increasing prevalence and is one of the most intractable clinical challenges in the field of reproductive medicine. Quercetin (QCT) is an effective active ingredient extracted from Semen Cuscutae and Herba Taxilli used in traditional Chinese medicine for tonifyng the kidneys and promoting fetal restoration. Although QCT helps improve adverse pregnancy outcomes, the specific mechanism remains unclear. The trophoblast cell line HTR‐8/SVneo cultured in vitro was treated with different concentrations of QCT, and the cell counting kit‐8 assay, wound healing assay, transwell assay, and western blotting were used to evaluate the effects and mechanisms of QCT on the proliferation, migration, and invasion of HTR‐8/SVneo cells, respectively. To assess the expression levels of miR‐149‐3p and AKT serine/threonine kinase 1 (AKT1), quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blotting analysis were performed. A dual‐luciferase reporter assay was used to investigate the potential regulatory relationship between miR‐149‐3p and AKT1. Our results showed that QCT promoted the proliferation, migration, and invasion of trophoblast cells, promoted the expression of MMP2, MMP9, and vimentin, and downregulated the expression of E‐cadherin. Mechanistically, QCT downregulated the expression of miR‐149‐3p and upregulated the expression of AKT1, and miR‐149‐3p directly targets AKT1, negatively regulating its expression. Overexpression of miR‐149‐3p and silencing of AKT1 counteracted the promotional effects of QCT on trophoblast proliferation, migration, and invasion. Taken together, QCT regulates the migration and invasion abilities of HTR‐8/SVneo cells through the miR‐149‐3p/AKT1 axis, which may provide a promising therapeutic approach for RSA.

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FPR2 serves a role in recurrent spontaneous abortion by regulating trophoblast function via the PI3K/AKT signaling pathway

Cited by 11 publications

References 48 publications

Vertical Intrauterine Bovine and Ovine Papillomavirus Coinfection in Pregnant Cows

Vertical Intrauterine Bovine and Ovine Papillomavirus Coinfection in Pregnant Cows

Effects of N Acetylcysteine on the Expression of Genes Associated with Reproductive Performance in the Goat Uterus during Early Gestation

Quercetin promotes the proliferation, migration, and invasion of trophoblast cells by regulating the miR‐149‐3p/AKT1 axis

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