{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T00:00:08Z","timestamp":1793664008225,"version":"4.5.1"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,5,29]],"date-time":"2021-05-29T00:00:00Z","timestamp":1622246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31970800"],"award-info":[{"award-number":["31970800"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Program for International Science and Technology Cooperation Projects of China","award":["81820108016"],"award-info":[{"award-number":["81820108016"]}]},{"name":"National Key R&D Program of China","award":["2019YFA0110900"],"award-info":[{"award-number":["2019YFA0110900"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Polycystic ovary syndrome (PCOS) is a prevalent heterogeneous endocrine disorder characterized by ovulation dysfunction, androgen excess, ovarian polycystic changes, insulin resistance, and infertility. Although underlying mechanisms for PCOS are still unknown, inflammation and mitochondrial dysfunction in granulosa cells (GCs) of PCOS patients have been reported. Here, we found that Nicotinamide Adenine Dinucleotide (NAD+) levels in GCs of PCOS patients was significantly decreased when compared with controls. Also, we found that higher expression of inflammation factors, increased reactive oxygen species (ROS) accumulation, lower adenosine triphosphate (ATP) generation, and decreased mitochondrial membrane potential, as well as abnormal mitochondrial dynamics in GCs of PCOS patients. In addition, the NAD+ levels were decreased after activation of inflammation in human granulosa-like tumor cell line (KGN) treated by Lipopolysaccharide (LPS). However, supplementation of nicotinamide riboside (NR), a NAD+ precursor, could largely restore the NAD+ content, reduce ROS levels and improve mitochondrial function demonstrated by increased mitochondrial membrane potential and ATP generation in LPS-treated KGN cells. Our data suggested that inflammation decreased NAD+ levels in GCs of PCOS patients, while supplementation of NR could restore NAD+ levels and alleviated mitochondrial dysfunction in GCs of PCOS patients.<\/jats:p>","DOI":"10.1093\/biolre\/ioab078","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T01:29:30Z","timestamp":1622424570000},"page":"371-380","source":"Crossref","is-referenced-by-count":74,"title":["NAD+ deficiency and mitochondrial dysfunction in granulosa cells of women with polycystic ovary syndrome\u2021"],"prefix":"10.1093","volume":"105","author":[{"given":"Yujiao","family":"Wang","sequence":"first","affiliation":[{"name":"Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"},{"name":"Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"},{"name":"Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"},{"name":"Henan Engineering Laboratory of Preimplantation Genetic Diagnosis and Screening, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingling","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"},{"name":"Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"},{"name":"Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"},{"name":"Henan Engineering Laboratory of Preimplantation Genetic Diagnosis and Screening, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"},{"name":"Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"},{"name":"Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"},{"name":"Henan Engineering Laboratory of Preimplantation Genetic Diagnosis and Screening, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"},{"name":"Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"},{"name":"Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"},{"name":"Henan Engineering Laboratory of Preimplantation Genetic Diagnosis and Screening, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luping","family":"Cong","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"},{"name":"Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"},{"name":"Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"},{"name":"Henan Engineering Laboratory of Preimplantation Genetic Diagnosis and Screening, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"},{"name":"Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"},{"name":"Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"},{"name":"Henan Engineering Laboratory of Preimplantation Genetic Diagnosis and Screening, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingpu","family":"Sun","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"},{"name":"Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"},{"name":"Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"},{"name":"Henan Engineering Laboratory of Preimplantation Genetic Diagnosis and Screening, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,5,29]]},"reference":[{"key":"2021080406594763500_ref1","doi-asserted-by":"crossref","first-page":"7435","DOI":"10.1002\/jcp.27501","article-title":"Dehydroepiandrosterone stimulates inflammation and impairs ovarian functions of polycystic ovary syndrome","volume":"234","year":"2019","journal-title":"J Cell Physiol"},{"key":"2021080406594763500_ref2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.fertnstert.2003.10.004","article-title":"Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome","volume":"81","author":"Rotterdam","year":"2004","journal-title":"Fertil Steril"},{"key":"2021080406594763500_ref3","first-page":"1","article-title":"Oxidative stress in granulosa cells contributes to poor oocyte quality and IVF-ET outcomes in women with polycystic ovary syndrome","volume":"12","author":"","year":"2017","journal-title":"Front Med"},{"key":"2021080406594763500_ref4","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1210\/jc.2014-2419","article-title":"Up-regulated expression of WNT5a increases inflammation and oxidative stress via PI3K\/AKT\/NF-kappaB signaling in the granulosa cells of PCOS patients","volume":"100","author":"","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"2021080406594763500_ref5","doi-asserted-by":"crossref","first-page":"R219","DOI":"10.1530\/REP-14-0435","article-title":"Adipose tissue dysfunction, adipokines, and low-grade chronic inflammation in polycystic ovary syndrome","volume":"149","year":"2015","journal-title":"Reproduction"},{"key":"2021080406594763500_ref6","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1016\/j.metabol.2006.04.002","article-title":"Plasma interleukin 6 levels are elevated in polycystic ovary syndrome independently of obesity or sleep apnea","volume":"55","year":"2006","journal-title":"Metabolism"},{"key":"2021080406594763500_ref7","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1210\/jc.2005-2327","article-title":"Increased activation of nuclear factor kappaB triggers inflammation and insulin resistance in polycystic ovary syndrome","volume":"91","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"2021080406594763500_ref8","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/0002-9378(84)90769-5","article-title":"Aromatase activity in human granulosa cells during follicular development and the modulation by follicle-stimulating hormone and insulin","volume":"148","author":"Garzo","year":"1984","journal-title":"Am J Obstet Gynecol"},{"key":"2021080406594763500_ref9","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1016\/S0093-691X(02)01190-1","article-title":"Apoptosis within bovine follicular cells and its effect on oocyte development during in vitro 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