@article{f45dfad14af447218c1f69a29e9ac45f,
title = "A high-androgen microenvironment inhibits granulosa cell proliferation and alters cell identity",
abstract = "A naturally occurring bovine model with excess follicular fluid androstenedione (High A4), reduced fertility, and polycystic ovary syndrome (PCOS)-like characteristics has been identified. We hypothesized High A4 granulosa cells (GCs) would exhibit altered cell proliferation and/or steroidogenesis. Microarrays of Control and High A4 GCs combined with Ingenuity Pathway Analysis indicated that High A4 GCs had cell cycle inhibition and increased expression of microRNAs that inhibit cell cycle genes. Granulosa cell culture confirmed that A4 treatment decreased GC proliferation, increased anti-M{\"u}llerian hormone, and increased mRNA for CTNNBIP1. Increased CTNNBIP1 prevents CTNNB1 from interacting with members of the WNT signaling pathway thereby inhibiting the cell cycle. Expression of CYP17A1 was upregulated in High A4 GCs presumably due to reduced FOS mRNA expression compared to Control granulosa cells. Furthermore, comparisons of High A4 GC with thecal and luteal cell transcriptomes indicated an altered cellular identity and function contributing to a PCOS-like phenotype.",
keywords = "AMH, Bovine granulosa, Cell cycle arrest, Cell identity, Excess androgens, Transcriptome",
author = "McFee, {Renee M.} and Romereim, {Sarah M.} and Snider, {Alexandria P.} and Summers, {Adam F.} and Pohlmeier, {William E.} and Kurz, {Scott G.} and Cushman, {Robert A.} and Davis, {John S.} and Wood, {Jennifer R.} and Cupp, {Andrea S.}",
note = "Funding Information: This research was supported by USDA-National Institute of Food and Agriculture 2013-67015-20965 and 2017-67015-26450 to ASC, JRW and JSD, University of Nebraska Foundation-Food for Health Competitive Grants to ASC, JSD, and JRW. United States Department of Agriculture Hatch grant NEB26-202/W3112 Accession #1011127 to ASC, United States Department of Agriculture Hatch–NEB Animal Health (ANHL) Accession #1002234 to ASC and JRW and USDA-NIFA postdoctoral fellowship 2016-67012-24697 to SR, USDA-NIFA postdoctoral fellowship 2019-67012-29624 to AS. JSD is a recipient of a Senior Research Career Scientist award from the Department of Veterans Affairs . Funding Information: The authors would like to acknowledge the assistance of the University of Nebraska Medical Center Genomics Core Facility for performing the microarrays and the University of Nebraska-Lincoln Department of Statistics for their help in incorporating the Principal Component Analysis. The University of Nebraska Medical Center Genomics Core receives partial support from the National Institute for General Medical Science ( NIGMS ) INBRE - P20GM103427-14 and NIH COBRE - 1P30GM110768-01 grants as well as The Fred & Pamela Buffett Cancer Center Support Grant - P30CA036727. This publication's contents are the sole responsibility of the authors and do not necessarily represent the official views of the NIH or NIGMS. Funding Information: This research was supported by USDA-National Institute of Food and Agriculture 2013-67015-20965 and 2017-67015-26450 to ASC, JRW and JSD, University of Nebraska Foundation-Food for Health Competitive Grants to ASC, JSD, and JRW. United States Department of Agriculture Hatch grant NEB26-202/W3112 Accession #1011127 to ASC, United States Department of Agriculture Hatch–NEB Animal Health (ANHL) Accession #1002234 to ASC and JRW and USDA-NIFA postdoctoral fellowship 2016-67012-24697 to SR, USDA-NIFA postdoctoral fellowship 2019-67012-29624 to AS. JSD is a recipient of a Senior Research Career Scientist award from the Department of Veterans Affairs.The authors would like to acknowledge the assistance of the University of Nebraska Medical Center Genomics Core Facility for performing the microarrays and the University of Nebraska-Lincoln Department of Statistics for their help in incorporating the Principal Component Analysis. The University of Nebraska Medical Center Genomics Core receives partial support from the National Institute for General Medical Science (NIGMS) INBRE - P20GM103427-14 and NIH COBRE - 1P30GM110768-01 grants as well as The Fred & Pamela Buffett Cancer Center Support Grant - P30CA036727. This publication's contents are the sole responsibility of the authors and do not necessarily represent the official views of the NIH or NIGMS. Publisher Copyright: {\textcopyright} 2021 Elsevier B.V.",
year = "2021",
month = jul,
day = "1",
doi = "10.1016/j.mce.2021.111288",
language = "English (US)",
volume = "531",
journal = "Molecular and Cellular Endocrinology",
issn = "0303-7207",
publisher = "Elsevier Ireland Ltd",
}