Tankyrase inhibition regulates corpus luteum development and luteal function in gonadotropin-treated rats
Paula Accialini1, Griselda Irusta1, Andrés Bechis1,2
1Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina.
Abstract:
Tankyrases are physiological regulators of Axin, a protein involved in several cellular processes, including Wnt signaling. Here, we investigated the effect of a specific Tankyrase inhibitor (XAV939) in follicular-luteal dynamics, and its possible relationship with ovarian vascular development. Studies were designed to analyze the effect of intrabursa administration of XAV939 in gonadotropin-treated prepubertal rats. In particular, we examined follicle and corpus luteum development, steroidogenesis, angiogenic markers, and apoptotic parameters. We found that in vivo inhibition of Wnt signaling impaired corpus luteum development, with a decrease in the number of corpora lutea balanced by a high number of cysts; decreased circulating progesterone levels, likely due to a decrease in Steroidogenic acute regulatory protein content in the corpus luteum; and increased pro-apoptotic parameters. In addition, Extracellular signal-regulated kinase phosphorylation, Vascular endothelium growth factor 120 content, and endothelial cell area were diminished in corpora lutea of inhibitor-treated ovaries. Thus, Wnt/β-catenin signaling appears to participate in the regulation of corpus luteum development and luteal cell function.
Insights
Inhibiting Tankyrase (a Wnt signaling regulator) disrupted corpus luteum development and function in rats. This Wnt/β-catenin pathway is crucial for ovarian vascularization and progesterone production.
Area of Science:
- Reproductive biology
- Endocrinology
- Molecular signaling
Background:
- Tankyrases regulate Axin, a key component of Wnt signaling pathways.
- Wnt signaling is implicated in various cellular processes, including ovarian function.
- Ovarian dynamics involve complex hormonal and cellular interactions.
Purpose of the Study:
- To investigate the impact of a Tankyrase inhibitor (XAV939) on follicular-luteal dynamics.
- To explore the relationship between Wnt signaling inhibition and ovarian vascular development.
- To assess the effects on corpus luteum formation, steroidogenesis, and apoptosis.
Main Methods:
- Intrabursal administration of XAV939 in gonadotropin-treated prepubertal rats.
- Analysis of follicle and corpus luteum development.
- Measurement of circulating progesterone, angiogenic markers, and apoptotic parameters.
Main Results:
- Tankyrase inhibition impaired corpus luteum development, leading to fewer corpora lutea and more cysts.
- Reduced circulating progesterone levels were observed, linked to decreased Steroidogenic acute regulatory protein.
- Increased pro-apoptotic markers and diminished vascular endothelial growth factor (VEGF) and endothelial cell area in corpora lutea.
Conclusions:
- Wnt/β-catenin signaling is essential for regulating corpus luteum development and function.
- Inhibition of this pathway negatively affects luteal vascularization and steroidogenesis.
- Tankyrase inhibition provides insights into the molecular mechanisms governing ovarian cyclicity.
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