Cellular localization, expression and functional implications of the utero-placental endothelin system during maintenance and termination of canine gestation

Abstract

Utero-placental (Ut-Pl) angiogenesis and blood flow are fundamental for successful outcome of pregnancy. They are controlled by numerous vasodilator and vasoconstrictor systems such as endothelins (EDNs) and the renin angiotensin system. Dogs possess an invasive type of placentation, classified as endotheliochorial. Despite increasing knowledge regarding canine Ut-Pl function, little information exists on uterine and placental vascular activity during initiation, maintenance and termination of pregnancy in this species. The current study investigated expression of EDNs and their receptors (EDNRA and EDNRB) in the pre-implantation uterus and Ut-Pl compartments during gestation and at normal parturition, as well as in mid-pregnant dogs treated with the antigestagen aglepristone. The Ut-Pl mRNA expression of EDN1 and EDNRA was constant until mid-gestation and increased significantly during prepartum luteolysis. In contrast, EDN2 was highest pre-implantation and decreased following placentation, remaining low thereafter. Expression of the EDN-activating enzyme ECE1 and mRNA of EDNRB increased towards mid-gestation and was further elevated at prepartum luteolysis. Antigestagen treatment resulted in increased levels of EDN1 and EDNRA. At the cellular level, the uterine expression of EDN1, ECE1 and EDNRB was found predominantly in the endometrial surface and glandular epithelial cells; uterine signals for EDNRA were weak. In Ut-Pl all targets were mainly localized in the placenta fetalis, with syncytiotrophoblast staining stronger for ECE1 and EDNRB. In contrast, EDNRA stained strongly at the base of the placental labyrinth. Expression and localization of EDNs (EDN1, -2), EDN receptors and ECE1 in the placenta fetalis suggests their involvement in the trophoblast invasion and proliferation.

Effect of cold stress on ovarian & uterine microcirculation in rats and the role of endothelin system

“…Cold exposure not only directly triggers an increase in plasma endothelin secretion but also causes vascular smooth muscle cell contraction, vasospasm, emboli, and even local tissue ischemia and edema. In addition, ET is also expressed in ovarian and uterine tissues [19,20], which is considered a regulatory reproductive hormone peptide. It plays an important role in regulating reproductive hormone secretion, animal reproductive function, muscle contraction, and cell mitosis.…”

Gene profiling reveals the role of inflammation, abnormal uterine muscle contraction and vascularity in recurrent implantation failure

“…EDNRB widely locates in vascular endothelium of many human tissues including placenta (Gram et al, 2017). The expression of EDNRB was increased in the perivascular and vascular cells of branching vessels during the late secretory phase (Keator et al, 2011).…”

“…The expression of EDNRB was increased in the perivascular and vascular cells of branching vessels during the late secretory phase (Keator et al, 2011). And EDNRB was constantly expressed during pregnancy including peri-implantation phase (Gram et al, 2017). What intrigues us is that during prepartum luteolysis, elevated expression of the EDN receptors in placenta strongly resembles the placental localization of PGs family members (e.g., PTGS2) in dogs (Kowalewski et al, 2010;Gram et al, 2014).…”

Integrated Analysis of DNA Methylation and Gene Expression in Porcine Placental Development

“…Our results showed that the gene transcription of some genes involved in blood vessel development and the apelin signaling pathway were regulated by DNA methylation during placental development, including EDN2 , APLN , and ALDH2 . Utero-placental angiogenesis and blood flow are controlled by numerous vasodilator and vasoconstrictor systems, such as endothelins (EDNs) and the renin angiotensin system [ 53 ]. EDN2 is one of the ENDs and exhibits strong vasoconstricting activity.…”

“…EDN2 is one of the ENDs and exhibits strong vasoconstricting activity. EDN2 mRNA is localized to the endometrial luminal epithelial cells and glandular epithelial cells at pre-implantation [ 53 ]. Our results showed that EDN2 had the highest expression in p35, and that gene transcription might be controlled by DNA methylation.…”