Downregulation of fascin in the first trimester placental villi is associated with early recurrent miscarriage

Inadequate trophoblast proliferation, shallow invasion and exaggerated rate of trophoblast apoptosis are implicated in early recurrent miscarriage (ERM). However, the mechanistic bases of this association have not been fully established. We aimed at investigating the involvement of fascin, an actin-...

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Vydané v:	Experimental cell research Ročník 403; číslo 1; s. 112597
Hlavní autori:	Lamptey, Jones, Li, Fangfang, Adu-Gyamfi, Enoch Appiah, Chen, Xue-Mei, Czika, Armin, Otoo, Antonia, Liu, Tai-Hang, Wang, Ying-Xiong, Ding, Yu-Bin
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Elsevier Inc 01.06.2021
Predmet:	60 APPLIED LIFE SCIENCES ACTIN ANOXIA APOPTOSIS CELL PROLIFERATION Fascin Hypoxia reoxygenation MOLECULES MORPHOLOGY PATHOGENESIS PHOSPHOTRANSFERASES PREGNANCY Recurrent miscarriage TRANSCRIPTION FACTORS Trophoblast Recurrent miscarriage Trophoblast Hypoxia reoxygenation Fascin
ISSN:	0014-4827, 1090-2422, 1090-2422
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Abstract	Inadequate trophoblast proliferation, shallow invasion and exaggerated rate of trophoblast apoptosis are implicated in early recurrent miscarriage (ERM). However, the mechanistic bases of this association have not been fully established. We aimed at investigating the involvement of fascin, an actin-bundling protein, in trophoblast activities and ERM. We found that fascin was downregulated in the cytotrophoblasts (CTBs) and distal cytotrophoblasts (DCTs) of ERM placentae. Knockdown of fascin altered cellular and nucleolar morphology, and inhibited the proliferation but increased apoptosis of trophoblastic HTR8/SVneo cells. Furthermore, fascin knockdown decreased the expression of transcription factors such as Snail1/2, Twist and Zeb1/2, mesenchymal molecules such as Vimentin and N-cadherin, and the protein expression of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylates signal transducer and activator of transcript 3 (STAT3). Exposure of HTR-8/SVneo cells to hypoxia reoxygenation (H/R) decreased fascin expression to affect the cells’ invasion. Our results indicate for the first time that the downregulation of fascin is involved in the pathogenesis of early recurrent miscarriage; and hence a potential therapeutic target against the disease. •Fascin is downregulated in the placentae of pregnancies complicated by early recurrent miscarriage.•Knockdown of fascin decreased HTR-8/SVneo cells' proliferation, migration and invasion.•Fascin knockdown decreased phosphorylated ERK1/2 and phosphorylated STAT3 protein level in HTR-8/SVneo cells.•Hypoxia reoxygenation decreased fascin, N-Cadherin and Vimentin protein levels to affect HTR-8/SVneo cells' invasion.
AbstractList	Inadequate trophoblast proliferation, shallow invasion and exaggerated rate of trophoblast apoptosis are implicated in early recurrent miscarriage (ERM). However, the mechanistic bases of this association have not been fully established. We aimed at investigating the involvement of fascin, an actin-bundling protein, in trophoblast activities and ERM. We found that fascin was downregulated in the cytotrophoblasts (CTBs) and distal cytotrophoblasts (DCTs) of ERM placentae. Knockdown of fascin altered cellular and nucleolar morphology, and inhibited the proliferation but increased apoptosis of trophoblastic HTR8/SVneo cells. Furthermore, fascin knockdown decreased the expression of transcription factors such as Snail1/2, Twist and Zeb1/2, mesenchymal molecules such as Vimentin and N-cadherin, and the protein expression of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylates signal transducer and activator of transcript 3 (STAT3). Exposure of HTR-8/SVneo cells to hypoxia reoxygenation (H/R) decreased fascin expression to affect the cells' invasion. Our results indicate for the first time that the downregulation of fascin is involved in the pathogenesis of early recurrent miscarriage; and hence a potential therapeutic target against the disease. Inadequate trophoblast proliferation, shallow invasion and exaggerated rate of trophoblast apoptosis are implicated in early recurrent miscarriage (ERM). However, the mechanistic bases of this association have not been fully established. We aimed at investigating the involvement of fascin, an actin-bundling protein, in trophoblast activities and ERM. We found that fascin was downregulated in the cytotrophoblasts (CTBs) and distal cytotrophoblasts (DCTs) of ERM placentae. Knockdown of fascin altered cellular and nucleolar morphology, and inhibited the proliferation but increased apoptosis of trophoblastic HTR8/SVneo cells. Furthermore, fascin knockdown decreased the expression of transcription factors such as Snail1/2, Twist and Zeb1/2, mesenchymal molecules such as Vimentin and N-cadherin, and the protein expression of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylates signal transducer and activator of transcript 3 (STAT3). Exposure of HTR-8/SVneo cells to hypoxia reoxygenation (H/R) decreased fascin expression to affect the cells' invasion. Our results indicate for the first time that the downregulation of fascin is involved in the pathogenesis of early recurrent miscarriage; and hence a potential therapeutic target against the disease.Inadequate trophoblast proliferation, shallow invasion and exaggerated rate of trophoblast apoptosis are implicated in early recurrent miscarriage (ERM). However, the mechanistic bases of this association have not been fully established. We aimed at investigating the involvement of fascin, an actin-bundling protein, in trophoblast activities and ERM. We found that fascin was downregulated in the cytotrophoblasts (CTBs) and distal cytotrophoblasts (DCTs) of ERM placentae. Knockdown of fascin altered cellular and nucleolar morphology, and inhibited the proliferation but increased apoptosis of trophoblastic HTR8/SVneo cells. Furthermore, fascin knockdown decreased the expression of transcription factors such as Snail1/2, Twist and Zeb1/2, mesenchymal molecules such as Vimentin and N-cadherin, and the protein expression of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylates signal transducer and activator of transcript 3 (STAT3). Exposure of HTR-8/SVneo cells to hypoxia reoxygenation (H/R) decreased fascin expression to affect the cells' invasion. Our results indicate for the first time that the downregulation of fascin is involved in the pathogenesis of early recurrent miscarriage; and hence a potential therapeutic target against the disease. Highlights: • Fascin is downregulated in the placentae of pregnancies complicated by early recurrent miscarriage. • Knockdown of fascin decreased HTR-8/SVneo cells' proliferation, migration and invasion. • Fascin knockdown decreased phosphorylated ERK1/2 and phosphorylated STAT3 protein level in HTR-8/SVneo cells. • Hypoxia reoxygenation decreased fascin, N-Cadherin and Vimentin protein levels to affect HTR-8/SVneo cells' invasion. Inadequate trophoblast proliferation, shallow invasion and exaggerated rate of trophoblast apoptosis are implicated in early recurrent miscarriage (ERM). However, the mechanistic bases of this association have not been fully established. We aimed at investigating the involvement of fascin, an actin-bundling protein, in trophoblast activities and ERM. We found that fascin was downregulated in the cytotrophoblasts (CTBs) and distal cytotrophoblasts (DCTs) of ERM placentae. Knockdown of fascin altered cellular and nucleolar morphology, and inhibited the proliferation but increased apoptosis of trophoblastic HTR8/SVneo cells. Furthermore, fascin knockdown decreased the expression of transcription factors such as Snail1/2, Twist and Zeb1/2, mesenchymal molecules such as Vimentin and N-cadherin, and the protein expression of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylates signal transducer and activator of transcript 3 (STAT3). Exposure of HTR-8/SVneo cells to hypoxia reoxygenation (H/R) decreased fascin expression to affect the cells’ invasion. Our results indicate for the first time that the downregulation of fascin is involved in the pathogenesis of early recurrent miscarriage; and hence a potential therapeutic target against the disease. Inadequate trophoblast proliferation, shallow invasion and exaggerated rate of trophoblast apoptosis are implicated in early recurrent miscarriage (ERM). However, the mechanistic bases of this association have not been fully established. We aimed at investigating the involvement of fascin, an actin-bundling protein, in trophoblast activities and ERM. We found that fascin was downregulated in the cytotrophoblasts (CTBs) and distal cytotrophoblasts (DCTs) of ERM placentae. Knockdown of fascin altered cellular and nucleolar morphology, and inhibited the proliferation but increased apoptosis of trophoblastic HTR8/SVneo cells. Furthermore, fascin knockdown decreased the expression of transcription factors such as Snail1/2, Twist and Zeb1/2, mesenchymal molecules such as Vimentin and N-cadherin, and the protein expression of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylates signal transducer and activator of transcript 3 (STAT3). Exposure of HTR-8/SVneo cells to hypoxia reoxygenation (H/R) decreased fascin expression to affect the cells’ invasion. Our results indicate for the first time that the downregulation of fascin is involved in the pathogenesis of early recurrent miscarriage; and hence a potential therapeutic target against the disease. •Fascin is downregulated in the placentae of pregnancies complicated by early recurrent miscarriage.•Knockdown of fascin decreased HTR-8/SVneo cells' proliferation, migration and invasion.•Fascin knockdown decreased phosphorylated ERK1/2 and phosphorylated STAT3 protein level in HTR-8/SVneo cells.•Hypoxia reoxygenation decreased fascin, N-Cadherin and Vimentin protein levels to affect HTR-8/SVneo cells' invasion.
ArticleNumber	112597
Author	Liu, Tai-Hang Wang, Ying-Xiong Czika, Armin Lamptey, Jones Adu-Gyamfi, Enoch Appiah Otoo, Antonia Chen, Xue-Mei Ding, Yu-Bin Li, Fangfang
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CitedBy_id	crossref_primary_10_3389_fimmu_2023_1331964 crossref_primary_10_1007_s43032_024_01555_2 crossref_primary_10_1016_j_tice_2021_101662 crossref_primary_10_26508_lsa_202302247 crossref_primary_10_1016_j_yexcr_2022_113428 crossref_primary_10_1007_s11033_024_09220_2 crossref_primary_10_1016_j_yexcr_2021_112885 crossref_primary_10_1016_j_theriogenology_2025_117499 crossref_primary_10_4014_jmb_2112_12056 crossref_primary_10_1016_j_placenta_2021_06_004 crossref_primary_10_1016_j_jri_2022_103666 crossref_primary_10_1177_09603271231163476
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Keywords	Recurrent miscarriage Trophoblast Hypoxia reoxygenation Fascin
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Snippet	Inadequate trophoblast proliferation, shallow invasion and exaggerated rate of trophoblast apoptosis are implicated in early recurrent miscarriage (ERM).... Highlights: • Fascin is downregulated in the placentae of pregnancies complicated by early recurrent miscarriage. • Knockdown of fascin decreased HTR-8/SVneo...
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SubjectTerms	60 APPLIED LIFE SCIENCES ACTIN ANOXIA APOPTOSIS CELL PROLIFERATION Fascin Hypoxia reoxygenation MOLECULES MORPHOLOGY PATHOGENESIS PHOSPHOTRANSFERASES PREGNANCY Recurrent miscarriage TRANSCRIPTION FACTORS Trophoblast
Title	Downregulation of fascin in the first trimester placental villi is associated with early recurrent miscarriage
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