This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.
The regulation of corpus luteus (CL) luteolysis is a complex process involving a myriad of factors. Previously, we have shown the involvement of Nodal in functional luteolysis in mares. Presently, we ask the extent of which Nodal mediation of luteolysis is done through regulation of angioregression. We demonstrated the interaction between Nodal and hypoxia-inducible factor 1 α (HIF1α) and thrombospondin 1/thrombospondin receptor (TSP1/CD36) systems, could mediate angioregression during luteolysis. First, we demonstrated the inhibitory effect of Nodal on the vascular marker platelet/endothelial cell adhesion molecule 1 (CD31). Also, treatment of mid CL explants with vascular endothelial growth factor A (VEGFA) showed a trend on activin-like kinase 7 (Alk7) protein inhibition. Next, Nodal was also shown to activate HIF1α and in vitro culture of mid CL explants under decreased oxygen level promoted Nodal expression and SMAD family member 3 (Smad3) phosphorylation. In another experiment, the crosstalk between Nodal and TSP1/CD36 was investigated. Indeed, Nodal increased the expression of the anti-angiogenic TSP1 and its receptor CD36 in mid CL explants. Finally, the supportive effect of prostaglandin F2α (PGF2α) on TSP1/CD36 was blocked by SB431542 (SB), a pharmacological inhibitor of Nodal signaling. Thus, we evidenced for the first time the in vitro interaction between Nodal and both HIF1α and TSP1 systems, two conserved pathways previously shown to be involved in vascular regression during luteolysis. Considering the given increased expression of Nodal in mid CL and its role on functional luteolysis, the current results suggest the additional involvement of Nodal in angioregression during luteolysis in the mare, particularly in the activation of HIF1α and TSP1/CD36.
34Background/Aims: Obesity is associated with infertility, decreased ovarian 35 performance and lipotoxicity. However, little is known about the aetiology of these 36 reproductive impairments. Here, we hypothesise that the majority of changes in ovarian 37 physiology in diet-induced obesity (DIO) are a consequence of transcriptional changes 38 downstream of altered leptin signalling. Therefore, we investigated the extent to which 39 leptin signalling is altered in the ovary upon obesity with particular emphasis on effects 40 on cumulus cells (CCs), the intimate functional companions of the oocyte. Furthermore, 41we used the pharmacological hyperleptinemic (LEPT) mouse model to compare 42 transcriptional profiles to DIO. Methods: Mice were subjected to DIO for 4 and 16 43 weeks (wk) and leptin treatment for 16 days, to study effects in the ovary in components 44 of leptin signalling at the transcript and protein levels, using Western blot, Real-time 45 PCR and immunostaining. Furthermore, we used low-cell RNA sequencing to 46 characterise changes in the transcriptome of CCs in these models. Results: In the DIO 47 66
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.