Thrombospondin-1 at the crossroads of corpus luteum fate decisions

Abstract

The multimodular matricellular protein thrombospondin-1 (THBS1) was among the first identified endogenous antiangiogenic molecules. Recent studies have shown THBS1-mediated suppression of angiogenesis and other critical activities for corpus luteum (CL) regression. THBS1 is specifically induced by prostaglandin F2alpha in mature CL undergoing regression, whereas luteinizing signals such as luteinizing hormone and insulin reduced its expression. THBS1 interacts both synergistically and antagonistically with other essential luteal factors, such as fibroblast growth factor 2, transforming growth factor beta1 and serpin family E member 1, to promote vascular instability, apoptosis and matrix remodeling during luteal regression. Expression of THBS1 is also downregulated by pregnancy recognition signals to maintain the CL during early pregnancy. This dynamic pattern of luteal expression, the extensive interactivity with other luteal factors and strong antiangiogenic and proapoptotic activities indicate that THBS1 is a major determinant of CL fate.

The Interaction Between Nodal, Hypoxia-Inducible Factor 1 Alpha, and Thrombospondin 1 Promotes Luteolysis in Equine Corpus Luteum

“…Indeed, we have previously demonstrated that tumor necrosis factor-α anti-angiogenic role comprised TSP1 and its receptor CD36 activation in equine luteal cells (16). Furthermore, in bovine CL, PGF 2α induced-luteolysis mediated the upregulation of TSP1 and CD36 (10, 13, 36, 37), a finding which is in agreement with our former results. In the present study, we reported the upregulation of TSP1 and CD36 by Nodal in in vitro explants of equine mid CL.…”

“…In the present study, we used both PGF 2α and LH treatments as a positive controls for our culture system. Expectedly, PGF 2α amplified both TSP1 mRNA and protein and CD36 protein, as seen before in bovine CL (10, 13, 36, 37). However, no changes were seen on CD36 mRNA.…”

“…Importantly, TSP1 has been shown to be a downstream factor upregulated by HIF1α during hypoxia (35). Furthermore, the luteolytic role of TSP1 has been well-documented before (10). Indeed, we have previously demonstrated that tumor necrosis factor-α anti-angiogenic role comprised TSP1 and its receptor CD36 activation in equine luteal cells (16).…”

“…Overall, with mid CL explants we lose cell specificity on the response to our treatments, but we benefit from the contribution of the microvasculature to the response obtained. Thus, we studied the interaction between Nodal and HIF1α and TSP1/CD36 in mid CL explants, two vasoactive systems previously shown to play a role in CL luteolysis (9, 10).…”

“…Additionally, a well-characterized anti-angiogenic factor is the thrombospondin 1 (TSP1) (10). Previous studies revealed the reciprocal inhibitory action between TSP1 and the proangiogenic fibroblast growth factor 2 (FGF) (11).…”