Activation of YAP1 and TAZ enhances the in vitro maturation of yak oocytes and influences subsequent embryonic development

Donglan Zhong; Yangyang Pan; Meng Wang; Hui Zhang; Ruihua Xu; Qiyong Zuo; Tianhao Li; Sijiu Yu; Yan Cui

doi:10.1016/j.theriogenology.2025.117548

Activation of YAP1 and TAZ enhances the in vitro maturation of yak oocytes and influences subsequent embryonic development

Theriogenology. 2025 Jun 20:246:117548. doi: 10.1016/j.theriogenology.2025.117548. Online ahead of print.

Authors

Donglan Zhong¹, Yangyang Pan¹, Meng Wang¹, Hui Zhang¹, Ruihua Xu¹, Qiyong Zuo¹, Tianhao Li¹, Sijiu Yu², Yan Cui³

Affiliations

¹ College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, China; Gansu Livestock Embryo Engineering Technology Innovation Center, Lanzhou, 730070, China.
² College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, China; Gansu Livestock Embryo Engineering Technology Innovation Center, Lanzhou, 730070, China. Electronic address: sjyu@163.com.
³ College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, China; Gansu Livestock Embryo Engineering Technology Innovation Center, Lanzhou, 730070, China. Electronic address: cuiyan369@sina.com.

PMID: 40561881
DOI: 10.1016/j.theriogenology.2025.117548

Abstract

Obtaining high-quality in vitro matured oocytes is the basis for in vitro embryo production. In-depth analysis of the molecular mechanism of in vitro maturation of yak oocytes is crucial for the establishment of a standardized in vitro culture system. As a key transcriptional co-activator of the Hippo signaling pathway, YAP1/TAZ plays an important role by coordinating granulosa cell proliferation and estradiol synthesis, which are the core links of follicular development. However, the specific function of YAP1/TAZ in yak oocyte maturation remains unclear. Consequently, this study focuses on yaks as the research model, employing specific inhibitors and activators to modulate the activity of YAP1 and TAZ. By combining IVP, Western blotting, and immunofluorescence staining, we examined YAP1 and TAZ expression patterns and subcellular localization during oocyte maturation and blastocyst development. The objective is to elucidate the role of YAP1 and TAZ in regulating oocyte maturation and blastocyst quality. The results showed that YAP1 and TAZ proteins play a key role in yak oocyte maturation by changing their activity, which in turn significantly affects the expression of CYP17A1, CYP19A1 and CYP1A1, key enzymes in the CYP450 metabolic pathway. Furthermore, they modulate the expression of proteins involved in cumulus cell expansion, such as PTGS2, HAS2, and TNFAIP6, as well as oocyte-derived factors like GDF9 and BMP15 proteins. Significantly, the activity of YAP1 and TAZ influences both the total cell number and the differentiation of cell lineages in blastocysts. These results not only offer a novel perspective on the molecular mechanisms underlying reproductive regulation in plateau animals but also establish a crucial theoretical foundation for optimizing IVP technology in yaks and enhancing embryo production efficiency.

Keywords: CYP450s; Cell differentiation; IVM; TAZ; YAP1; Yak.