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

Abstract

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.

Roles of retrovirus-derived PEG10 and PEG11/RTL1 in mammalian development and evolution and their involvement in human disease

“…Knockdown of PEG11/RTL1 in cultured primary endothelial cells from the equine placental microvasculature resulted in the loss of sprouting ability, which is a fundamental process in neovascularization, further confirming the association between equine PEG11/RTL1 expression and endothelial cells and its importance in placental angiogenesis (Dini et al, 2021). Additionally, an association between abnormal expression of PEG11/RTL1 and the development of hydrallantois has been demonstrated (Dini et al, 2021). This suggests that PEG11/ RTL1 is also essential for placental angiogenesis, and that its abnormal expression could lead to placental dysfunction.…”

“…In horses (Equus caballus), PEG11/RTL1 is paternally expressed and localized within the endothelial cells of the equine chorioallantois (Dini et al, 2021). Knockdown of PEG11/RTL1 in cultured primary endothelial cells from the equine placental microvasculature resulted in the loss of sprouting ability, which is a fundamental process in neovascularization, further confirming the association between equine PEG11/RTL1 expression and endothelial cells and its importance in placental angiogenesis (Dini et al, 2021). Additionally, an association between abnormal expression of PEG11/RTL1 and the development of hydrallantois has been demonstrated (Dini et al, 2021).…”

Maternal RNA transcription in Dlk1-Dio3 domain is critical for proper development of the mouse placental vasculature

“…We found that two protein-coding genes located in Dlk1-Dio3 domain, Dlk1 and Rtl1 were upregulated in MKI and HOMO. Rtl1 was reported to play a crucial role in placental angiogenesis 38 . Some DEGs with significant changes and high expression levels were verified by qRT-PCR in Supplementary Fig.…”

Dynamics of the Equine Placental DNA Methylome and Transcriptome from Mid- to Late Gestation

“…Identifying the role of this gene in equine placenta angiogenesis could add valuable information to the reported genes already identified to have an effect in this process. In recent studies [ 68 , 69 , 70 ], several angiogenic genes ( ANGPT, VEGF, RTL1, VEGF, VEGFR1, ANGPT1, and eNOS) have been identified to show different gene expression patterns which can have an effect on placental development, placental function, and fetal size.…”