Iberian pig early pregnancy: Vascular endothelial growth factor receptor system expression in the maternofetal interface in healthy and arresting conceptuses

Fernández, Rubén Fuentes; Pérez, María Sotelo; Maldonado, B. Sánchez; García-Palencia, Pilar; Freixa, C. Naranjo; Yagüe, Antonio Palomo; Flores, Juana M.

doi:10.1016/j.theriogenology.2014.07.046

Cited by 7 publications

(7 citation statements)

References 24 publications

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“…Similar results were reported by several authors ( Vonnahme et al 2001 , Vonnahme & Ford 2004 , Guimarâes et al 2017) who found an increase in placental expression of the VEGF with advancement gestation in pigs. In addition, in Iberian pigs, VEGF mRNA and VEGFR2 mRNA expression was determined by García Fernández et al (2015) who observed an upregulated VEGF mRNA and VEGFR2 mRNA expression in the uterus, during early pregnancy.…”

Section: Discussionmentioning

confidence: 99%

“…Possibly, these findings were due to the activation of the VEGFA/KDR pathway to stimulate endothelial cell migration and proliferation in late-middle gestation. KDR signaling is therefore considered essential for the differentiation of endothelial precursor cells into vascular endothelial cells and their proliferation ( García Fernandez et al 2015 ). However, Sanchis et al (2015) have denoted the absence of VEGF in placental blood vessels, suggesting that angiogenesis in pigs during advanced gestation could be due to other angiogenic factors.…”

Section: Discussionmentioning

confidence: 99%

“…It is widely accepted that the formation of blood vessels occurs through the angiogenesis process, in which numerous angiogenic factors act by binding to specific receptors. The main factor involved in the regulation of vascular development is the vascular endothelial growth factor (VEGF) ( Vonnahme et al 2001 , Vonnahme & Ford 2004 , García Fernández et al 2015 , Sanchis et al 2015 , Guimarães et al 2017 ). During advance gestation in the pig, we have observed that angiogenic molecules, which are non-VEGF family members, induce angiogenesis ( Sanchis et al 2015 ).…”

Section: Introductionmentioning

confidence: 99%

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Placental vascularization in middle and late gestation in the pig

Fiorimanti

Cristofolini

Moreira‐Espinoza

et al. 2022

Reproduction and Fertility

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The aims of this study were to determine the changes in the capillary area density in relation to fetal development, to determine immunoexpression of angiogenic factors and to compare their mRNA expression throughout pig gestation. Samples were collected from the maternal-chorioallantoic interface at days 40, 77, 85 and 114 of pregnancy for immunohistochemistry analysis and the measurement of mRNA expression of VEGFA, ANGPT1, ANGPT2, FGF2 and its receptors KDR, TEK, FGFR1, FGFR2 respectively. Morphometric measurement of blood vessels was performed. We found a significant increase in capillary area density throughout gestation (P < 0.05). On the maternal side, at day 77, we observed a significant increase in the number of vessels from small vascular areas (P < 0.05) and the vascular area was significantly higher on day 85 (P < 0.05). On the fetal side, the number of vessels and the vascular area increased between days 40 and 77 (P < 0.05) and between days 77 and 114 (P < 0.05), respectively. Immunohistochemical findings revealed intense VEGFA staining and a trend for increased expression towards the end of gestation (P < 0.05). We also demonstrated a high VEGFA, FGF2, FGFR1, ANGPT1 and ANGPT2 mRNA expression at day 77 (P < 0.05). In conclusion, our findings suggest that an active angiogenesis would be present even until late-middle gestation at day 77 of pregnancy with the predominance of angiogenic stimulation by VEGFA / KDR, FGF2 / FGFR1 and a balance between ANGPT1 and ANGPT2/ TEK.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Placental vascularization in middle and late gestation in the pig

Fiorimanti

Cristofolini

Moreira‐Espinoza

et al. 2022

Reproduction and Fertility

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“…According to generally accepted guidelines, we distinguish between healthy and arresting embryos based on embryo size, weight, and vascularity of the placental membranes. When the embryo is relatively large and heavy, the blood vessels of the placental membrane are abundant, it is considered to be a healthy embryo, and when the state of the embryo is reversed, we define it as arresting embryo [ 6 , 8 , 52 ]. After statistics, the ratio between healthy embryos and arresting embryos is about 3:1–4:1.…”

Section: Methodsmentioning

confidence: 99%

Differential MicroRNA Expression in Porcine Endometrium Related to Spontaneous Embryo Loss during Early Pregnancy

Zang

Jiang

et al. 2022

IJMS

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Litter size is an important indicator to measure the production capacity of commercial pigs. Spontaneous embryo loss is an essential factor in determining sow litter size. In early pregnancy, spontaneous embryo loss in porcine is as high as 20–30% during embryo implantation. However, the specific molecular mechanism underlying spontaneous embryo loss at the end of embryo implantation remains unknown. Therefore, we comprehensively used small RNA sequencing technology, bioinformatics analysis, and molecular experiments to determine the microRNA (miRNA) expression profile in the healthy and arresting embryo implantation site of porcine endometrium on day of gestation (DG) 28. A total of 464 miRNAs were identified in arresting endometrium (AE) and healthy endometrium (HE), and 139 differentially expressed miRNAs (DEMs) were screened. We combined the mRNA sequencing dataset from the SRA database to predict the target genes of these miRNAs. A quantitative real-time PCR assay identified the expression levels of miRNAs and mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on differentially expressed target genes of DEMs, mainly enriched in epithelial development and amino acids metabolism-related pathways. We performed fluorescence in situ hybridization (FISH) and the dual-luciferase report gene assay to confirm miRNA and predicted target gene binding. miR-205 may inhibit its expression by combining 3′-untranslated regions (3′ UTR) of tubulointerstitial nephritis antigen-like 1 (TINAGL1). The resulting inhibition of angiogenesis in the maternal endometrium ultimately leads to the formation of arresting embryos during the implantation period. This study provides a reference for the effect of miRNA on the successful implantation of pig embryos in early gestation.

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“…The angiogenesis process depends on the expression of angiogenic factors such as vascular endothelial growth factor A (VEGFA) (Karaman et al, 2018; Simons et al, 2016; Vonnahme et al, 2001), angiopoietins (ANGPT1‐ANGPT2) (Wang & Lash, 2017) and basic fibroblast growth factor (bFGF or FGF2) (Welter et al, 2004) that act by binding to specific receptors such as Flt‐1 (VEGFR1) and KDR (VEGFR2 or Flk‐1), TEK2, FGFR1‐R2 respectively. While many studies have provided evidence for the differential expression of pro‐angiogenic growth factors and blood vessels development in the porcine placenta, the exact cause of spontaneous fetal loss is uncertain (Charnock‐Jones et al, 2001; Fiorimanti et al, 2022; Fiorimanti, Cristofolini, et al, 2018; Fiorimanti, Rabaglino, et al, 2018; García‐Fernández et al, 2015; Guimarães et al, 2017; Sanchis et al, 2015; Stenhouse et al, 2019; Vonnahme & Ford, 2004). During early gestation in pigs, significant morphological changes occur at the maternal–chorioallantoic interface, as a greater increase in placenta weight occurs between 37 and 42 days of gestation (Wright et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Vascular characterization and morphogenesis in porcine placenta at day 40 of gestation

Fiorimanti

Cristofolini

Rabaglino

et al. 2023

Reprod Domestic Animals

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In porcine placenta, abnormal development of the placental vasculature leads to placental insufficiency. The aim of this study was to determine the mRNA expression of angiogenic growth factors and to determine the vascular characteristics in placenta at day 40 of pig gestation. Samples were collected from maternal‐chorioallantoic interface (n = 21) for the measurement of mRNA expression of VEGFA, ANGPT1, ANGPT2, FGF2 and its receptors KDR, TEK, FGFR1IIIc, FGFR2IIIb respectively, and for immunohistochemistry analysis of CD31 and VEGFA. Immunohistochemical analysis of CD31 and VEGFA, morphometric measurement of blood vessels, high‐resolution light microscopy and transmission electron microscopy were performed. Capillary area density, number of blood vessels and capillary area were significantly higher on the maternal side than on the fetal side (p < .05). The ultrastructural finding of blood vessels demonstrates close contact with the trophoblastic epithelium. The relative mRNA expression of VEGFA and its receptor KDR was higher compared with the other angiogenic genes. In conclusion, a high mRNA expression of VEGFA and its receptor KDR added to the immunohistochemical results suggest a potential role of these genes in this pathway associated with an increase in the density of the capillary area on the maternal side and a reduction in the hemotrophic diffusion distance at the interface for nutrient exchange.

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Iberian pig early pregnancy: Vascular endothelial growth factor receptor system expression in the maternofetal interface in healthy and arresting conceptuses

Cited by 7 publications

References 24 publications

Placental vascularization in middle and late gestation in the pig

Placental vascularization in middle and late gestation in the pig

Differential MicroRNA Expression in Porcine Endometrium Related to Spontaneous Embryo Loss during Early Pregnancy

Vascular characterization and morphogenesis in porcine placenta at day 40 of gestation

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