@article{b43920386efe46c2865e75c308ce6bb2,
title = "Yes-associated protein 1 is required for proliferation and function of bovine granulosa cells in vitro",
abstract = "Yes-associated protein 1 (YAP1) is a major component of the Hippo signaling pathway. Although the exact extracellular signals that control the Hippo pathway are currently unknown, increasing evidence supports a critical role for the Hippo pathway in embryonic development, regulation of organ size, and carcinogenesis. Granulosa cells (GCs) within the ovarian follicle proliferate and produce steroids and growth factors, which facilitate the growth of follicle and maturation of the oocyte. We hypothesize that YAP1 plays a role in proliferation and estrogen secretion of GCs. In the current study, we examined the expression of the Hippo signaling pathway in bovine ovaries and determined whether it was important for GC proliferation and estrogen production. Mammalian STE20-like protein kinase 1 (MST1) and large tumor suppressor kinase 2 (LATS2) were identified as prominent upstream components of the Hippo pathway expressed in granulosa and theca cells of the follicle and large and small cells of the corpus luteum. Immunohistochemistry revealed that YAP1 was localized to the nucleus of growing follicles. In vitro, nuclear localization of the downstream Hippo signaling effector proteins YAP1 and transcriptional co-activator with PDZ-binding motif (TAZ) was inversely correlated with GC density, with greater nuclear localization under conditions of low cell density. Treatment with verteporfin and siRNA targeting YAP1 or TAZ revealed a critical role for these transcriptional co-activators in GC proliferation. Furthermore, knockdown of YAP1 in GCs inhibited follicle-stimulating hormone (FSH)-induced estradiol biosynthesis. The data indicate that Hippo pathway transcription co-activators YAP1/TAZ play an important role in GC proliferation and estradiol synthesis, two processes necessary for maintaining normal follicle development.",
keywords = "Hippo signaling, Yes-associated protein 1, bovine, follicular development, granulosa cells, proliferation, steroidogenesis",
author = "Plewes, {Michele R.} and Xiaoying Hou and Pan Zhang and Aixin Liang and Guohua Hua and Wood, {Jennifer R.} and Cupp, {Andrea S.} and Xiangmin Lv and Cheng Wang and Davis, {John S.}",
note = "Funding Information: † Plewes Michele R Hou Xiaoying Zhang Pan Liang Aixin Hua Guohua Wood Jennifer R Cupp Andrea S Lv Xiangmin Wang Cheng Davis John S jsdavis@unmc.edu Department of Obstetrics and Gynecology, Olson Center for Women's Health, University of Nebraska Medical Center , Omaha, NE, USA Veterans Affairs Nebraska Western Iowa Health Care System , Omaha, NE, USA College of Animal Science and Technology, Huazhong Agricultural University , Wuhan, China Department of Animal Sciences, University of Nebraska–Lincoln , Lincoln, NE, USA Correspondence: Olson Center for Women's Health, University of Nebraska Medical Center, 983255 Nebraska Medical Center, Omaha, NE 68198-3255, USA. Tel: 402 559-9079 ; Fax: 402 559-5015 ; E-mail: jsdavis@unmc.edu † Grant Support: This project was supported by Agriculture and Food Research Initiative Competitive Grant no. 2017-67015-26450 to JSD and 2018-67012-29531 to MRP from the USDA National Institute of Food and Agriculture; NIH grants R01 HD087402, R01HD092263, and P01AG029531; the Department of Veterans Affairs IBX004272; and The Olson Center for Women{\textquoteright}s Health. 11 2019 21 11 2019 09 08 2019 101 5 1001 1017 25 1 2019 28 5 2019 25 6 2019 25 6 2019 Published by Oxford University Press on behalf of Society for the Study of Reproduction 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US. 2019 This work is written by US Government employees and is in the public domain in the US. Funding Information: This project was supported by Agriculture and Food Research Initiative Competitive Grant no. 2017-67015-26450 to JSD and 2018-67012-29531 to MRP from the USDA National Institute of Food and Agriculture; NIH grants R01 HD087402, R01HD092263, and P01AG029531; the Department of Veterans Affairs IBX004272; and The Olson Center for Women's Health. Publisher Copyright: {\textcopyright} 2019 Published by Oxford University Press on behalf of Society for the Study of Reproduction 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.",
year = "2019",
month = nov,
day = "21",
doi = "10.1093/biolre/ioz139",
language = "English (US)",
volume = "101",
pages = "1001--1017",
journal = "Biology of Reproduction",
issn = "0006-3363",
publisher = "Society for the Study of Reproduction",
number = "5",
}