Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 541, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2021.111524
Keywords
Ovary; Cow; Hippo; Verteporfin; Peptide 17; EGF receptor
Categories
Funding
- Natural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN-2018-06470]
- Fonds Louis-Philippe Phaneuf (FMV-UdeM)
- Rio Grande do Sul State Research Support Foundation (FAPERGS -Edital June 2019, Brazil) [19/2551-0002275-1]
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This study demonstrates that YAP transcriptional activity is crucial for promoting ovulation through an LH-induced EGF-like cascade in monovulatory species like cattle.
Failure to ovulate is a major cause of infertility. The critical pathway that induces ovulation involves the EGF and MAPK phosphorylation, but studies in rodents have suggested that the Hippo activator, YAP, is also involved. It is unknown whether YAP-dependent transcriptional activity is important for the LH- or EGF-induced ovulatory cascade in monovulatory species such as the cow. Using a well-defined preovulatory GC culture system, we employed pharmacological inhibitors to demonstrate that YAP signaling is critical for expression of EGFR and downstream target genes EREG, EGR1 and TNFAIP6. Most importantly, by using an ultrasound guided follicle injection system, we also showed that the classic Hippo signaling inhibitor Verteporfin inhibits GnRH-induced ovulation in vivo in cattle. In conclusion, YAP transcriptional activity is critical for EGF-like cascade induced by LH to promote ovulation in a monovulatory species.
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