YAP signaling in preovulatory granulosa cells is critical for the functioning of the EGF network during ovulation

Area of Science:

• Reproductive Biology
• Cell Signaling
• Molecular Endocrinology

Background:

• Ovulation failure is a primary cause of infertility.
• The EGF and MAPK phosphorylation pathway is critical for ovulation, with potential involvement of YAP in rodents.
• The role of YAP in the ovulatory cascade of monovulatory species like cattle remains unclear.

Purpose of the Study:

• To investigate the role of YAP-dependent transcriptional activity in the LH- or EGF-induced ovulatory cascade in cows.
• To determine if YAP signaling is essential for the expression of key genes in the ovulatory process.
• To assess the in vivo effect of Hippo signaling inhibition on ovulation in cattle.

Main Methods:

• Utilized a preovulatory granulosa cell (GC) culture system with pharmacological inhibitors.
• Employed an ultrasound-guided follicle injection system for in vivo studies.
• Assessed the expression of EGFR and downstream genes (EREG, EGR1, TNFAIP6) and ovulation induction.

Main Results:

• YAP signaling was demonstrated to be critical for the expression of EGFR and downstream genes (EREG, EGR1, TNFAIP6) in cultured GC.
• The Hippo signaling inhibitor Verteporfin was shown to inhibit GnRH-induced ovulation in vivo in cattle.
• These findings highlight YAP's importance in the EGF-like cascade regulating ovulation.

Conclusions:

• YAP transcriptional activity is essential for the EGF-like cascade initiated by LH, which promotes ovulation in monovulatory species.
• The study establishes YAP as a key regulator in the bovine ovulatory process.
• Targeting YAP signaling presents a potential avenue for addressing infertility related to ovulation failure.