Equine hydrallantois is associated with impaired angiogenesis in the placenta

Dini, Pouya; Carossino, Mariano; Loynachan, Alan T.; Ali, Hesham A.; Wolfsdorf, Karen; Scoggin, Kirsten E.; Daels, Peter; Ball, Barry A.

doi:10.1016/j.placenta.2020.03.001

Cited by 13 publications

(20 citation statements)

References 85 publications

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“…This again suggests that the abnormal placental development and function in the cloned animal can be associated with the role of RTL1 in the placental vascular formation. Here, we also found that abnormal expression of RTL1 is associated with the development of hydrops in horses, a condition due to an abnormal vascular formation in the placenta [17]. Moreover, different donor cell lines used in nuclear transfer are associated with different degrees of placental abnormalities, which may be due to variation in the genomic regulation of RTL1 expression in different cells [69,70].…”

Section: Discussionmentioning

confidence: 52%

“…Similarly, abnormal conditions such as hydrops have also been reported in cloned horses and other cloned domestic animals [46]. Previously we demonstrated that abnormal angiogenesis leads to development of hydrops conditions in horses [17]. Based on this information, we hypothesized that RTL1 expression is involved in placental angiogenesis.…”

Section: Introductionmentioning

confidence: 72%

“…Previously, we demonstrated that a low number of vessels in equine chorioallantois lead to the development of hydrallantois [17]. However, the initial trigger, an underlying process for the abnormal angiogenesis in the placenta, is unknown.…”

Section: The Low Expression Of Rtl1 Is Associated With the Development Of Hydrallantoismentioning

confidence: 96%

“…In human pregnancy, failures in angiogenic processes are tightly linked to the development of placental pathologies, such as preeclampsia (PE), early pregnancy loss, and intrauterine growth restriction (IUGR) [15]. Previously, we demonstrated that abnormal angiogenesis in the equine placenta is associated with the development of hydrallantois, an excessive accumulation of fluid in placental membranes due to ineffective fluid exchange with alterations in fetal growth and resultant small fetuses [16,17].…”

Section: Introductionmentioning

confidence: 99%

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Paternally expressed retrotransposon Gag-like 1 gene, RTL1, is one of the crucial elements for placental angiogenesis in horses

Dini

Carossino

Balasuriya

et al. 2021

Biology of Reproduction

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RTL1 (retrotransposon Gag like 1) is an essential gene in the development of the human and murine placenta. Several fetal and placental abnormalities such as intrauterine growth restriction (IUGR) and hydrops conditions have been associated with altered expression of this gene. However, the function of RTL1 has not been identified. RTL1 is located on a highly conserved region in eutherian mammals. Therefore, the genetic and molecular analysis in horses could hold important implications for other species, including humans. Here we demonstrated that RTL1 is paternally expressed and is localized within the endothelial cells of the equine (Equus caballus) chorioallantois. We developed an equine placental microvasculature primary cell culture and demonstrated that RTL1 knock-down leads to loss of the sprouting ability of these endothelial cells. We further demonstrated an association between abnormal expression of RTL1 and development of hydrallantois. Our data suggest that RTL1 may be essential for placental angiogenesis, and its abnormal expression can lead to placental insufficiency. This placental insufficiency could be the reason for IUGR and hydrops conditions reported in other species, including humans.

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Section: Discussionmentioning

confidence: 52%

Section: Introductionmentioning

confidence: 72%

Section: The Low Expression Of Rtl1 Is Associated With the Development Of Hydrallantoismentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Paternally expressed retrotransposon Gag-like 1 gene, RTL1, is one of the crucial elements for placental angiogenesis in horses

Dini

Carossino

Balasuriya

et al. 2021

Biology of Reproduction

Self Cite

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“…During pregnancy, the functional and morphological changes in uteroplacental tissues occur in the uterine gland, the folded bilayer of trophoblast‐endometrial epithelia, blood vessels and the amniotic chorion (Burton, Kaufmann, & Huppertz, 2006). Endometrial remodelling and placentation are fundamental processes for foetal development and pregnancy maintenance, in which angiogenesis plays a core role (Dini et al., 2020). However, it is inevitable that diverse placental types have different structures and functions, such as the histological nature of the maternal–foetal interface, the microscopic structure of the folded bilayer of trophoblast–endometrial epithelia and the relative directions of maternal–foetal blood flows (Burton et al., 2006).…”

Section: Discussionmentioning

confidence: 99%

Spatiotemporal heterogeneity of PPARγ expression in porcine uteroplacenta for regulating of placental angiogenesis through VEGF‐mediated signalling

Zhang

Li-qun

Ang

et al. 2020

Reprod Domestic Animals

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Non-infectious prenatal mortality severely affects the porcine industry, with pathological placentation as a likely key reason. Previous studies have demonstrated that peroxisome proliferator-activated receptor gamma (PPARγ) deficiency causes defects in the uteroplacental vasculature and induces embryonic losses in mice. However, its role in porcine placental angiogenesis remains unclear. In the present study, PPARγ expression was investigated in porcine uteroplacental tissues at gestational day (GD) 25, GD40 and GD70 via quantitative polymerase chain reaction (qPCR), Western blot and immunohistochemistry (IHC). Moreover, the roles of PPARγ in porcine placental angiogenesis were investigated using a cell model of porcine umbilical vein endothelial cells (PUVECs) to conduct proliferation, migration and tube formation assays in vitro and a mouse xenograft model to assess capillary formation in vivo. The results showed that PPARγ was mainly located in the glandular epithelium, trophoblast, amniotic chorion epithelium and vascular endothelium, as indicated by the higher expression levels at GD25 and GD40 than at GD70 in endometrium and by higher expression levels at GD40 and GD70 than at GD25 in placenta. Moreover, PPARγ expression was significantly downregulated in placenta with dead foetus. In PUVECs, knocking out PPARγ significantly inhibited proliferation, migration and tube formation in vitro and inhibited capillary formation in mouse xenografts in vivo by blocking S-phase, promoting apoptosis and downregulating the angiogenic factors of VEGF and its receptors. Overall, the spatiotemporal heterogeneity of PPARγ expression in porcine uteroplacental tissue suggests its vital role in endometrial remodelling and placental angiogenesis, and PPARγ regulates placental angiogenesis through VEGFmediated signalling.

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Factors Affecting Survival and Future Foaling Rates in Thoroughbred Mares with Hydrops

Lemonnier

Wolfsdorf

Kreutzfeldt

et al. 2022

Journal of Equine Veterinary Science

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Equine hydrallantois is associated with impaired angiogenesis in the placenta

Cited by 13 publications

References 85 publications

Paternally expressed retrotransposon Gag-like 1 gene, RTL1, is one of the crucial elements for placental angiogenesis in horses

Paternally expressed retrotransposon Gag-like 1 gene, RTL1, is one of the crucial elements for placental angiogenesis in horses

Spatiotemporal heterogeneity of PPARγ expression in porcine uteroplacenta for regulating of placental angiogenesis through VEGF‐mediated signalling

Factors Affecting Survival and Future Foaling Rates in Thoroughbred Mares with Hydrops

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