{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:46:24Z","timestamp":1789991184889,"version":"4.0.1"},"reference-count":101,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T00:00:00Z","timestamp":1639699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81774136"],"award-info":[{"award-number":["81774136"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82074259"],"award-info":[{"award-number":["82074259"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009009","name":"Heilongjiang University of Chinese Medicine","doi-asserted-by":"publisher","award":["2018jc02"],"award-info":[{"award-number":["2018jc02"]}],"id":[{"id":"10.13039\/501100009009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>As a highly dynamic tissue, the endometrium is periodically shed in response to the secretion of estrogen and progesterone. After menarche, the endometrium of healthy women proliferates and differentiates under the action of steroid hormones (e.g., 17\u03b2-estradiol and progesterone) that are secreted by the ovaries to provide appropriate conditions for embryo implantation. Polycystic ovary syndrome (PCOS), a prevalent endocrine and metabolic disorder in reproductive-aged women, is usually associated with multiple cysts within the ovaries and excess levels of androgen and is characterized by hirsutism, acne, menstrual irregularity, infertility, and increased risk of insulin resistance. Multiple factors, such as anovulation, endocrine-metabolic abnormalities, and inflammation, can disrupt the endometrium in PCOS patients and can lead to endometrial hyperplasia, pregnancy complications, or even cancer. Despite many recent studies, the relationship between PCOS and abnormal endometrial function is still not fully understood. In this review, we investigate the correlation of PCOS patient endometrium with anovulation, hyperandrogenemia, insulin resistance, progesterone resistance, and inflammatory cytokines, aiming to provide a theoretical basis for the treatment of disorders caused by endometrial dysfunction in PCOS patients.<\/jats:p>","DOI":"10.3389\/fphys.2021.788772","type":"journal-article","created":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T01:48:10Z","timestamp":1639705690000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":49,"title":["Research Progress on the Mechanism Between Polycystic Ovary Syndrome and Abnormal Endometrium"],"prefix":"10.3389","volume":"12","author":[{"given":"Zhu","family":"Xue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanli","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxing","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoke","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"118003","DOI":"10.1016\/j.lfs.2020.118003","article-title":"Nanocurcumin alleviates insulin resistance and pancreatic deficits in polycystic ovary syndrome rats: insights on PI3K\/AkT\/mTOR and TNF-\u03b1 modulations","volume":"256","author":"Abuelezz","year":"2020","journal-title":"Life Sci."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2872","DOI":"10.3390\/ijms22062872","article-title":"Therapeutic potentials of low-dose tacrolimus for aberrant endometrial features in polycystic ovary syndrome","volume":"22","author":"Albaghdadi","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"6076274","DOI":"10.1155\/2020\/6076274","article-title":"Association of IL-1\u03b2, IL-6, TNF-\u03b1, and TGF\u03b21 gene polymorphisms with recurrent spontaneous abortion in polycystic ovary syndrome","volume":"2020","author":"Alkhuriji","year":"2020","journal-title":"Dis. Markers"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.mce.2011.10.035","article-title":"Mechanisms of endometrial progesterone resistance","volume":"358","author":"Al-Sabbagh","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1002\/cam4.244","article-title":"Prognostic significance of specific anti-WT1 IgG antibody level in plasma in patients with ovarian carcinoma","volume":"3","author":"Andersson","year":"2014","journal-title":"Cancer Med."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1016\/j.rbmo.2014.01.016","article-title":"Increased oxidation-related glutathionylation and carbonic anhydrase activity in endometriosis","volume":"28","author":"Andrisani","year":"2014","journal-title":"Reprod. Biomed. Online"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/s1071-5576(03)00147-3","article-title":"Progesterone up-regulates WT1 mRNA and protein, and alters the relative expression of WT1 transcripts in cultured endometrial stromal cells","volume":"10","author":"Anthony","year":"2003","journal-title":"J. Soc. Gynecol. Investig."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1080\/13813455.2018.1499120","article-title":"Insulin resistance and oxidative marker in women with PCOS","volume":"126","author":"Bannigida","year":"2020","journal-title":"Arch. Physiol. Biochem."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1530\/REP-09-0568","article-title":"The adverse effects of obesity on conception and implantation","volume":"140","author":"Brewer","year":"2010","journal-title":"Reproduction"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1210\/edrv.18.4.0308","article-title":"Physiological action of progesterone in target tissues","volume":"18","author":"Bulmer","year":"1997","journal-title":"Endocr. Rev."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"F1000","DOI":"10.12688\/f1000research.19132.1","article-title":"Uterine natural killer cells: time for a re-appraisal?","volume":"8","author":"Bulmer","year":"2019","journal-title":"F1000Res"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.3390\/cancers12051191","article-title":"The role of hyperglycemia in endometrial cancer pathogenesis","volume":"12","author":"Byrne","year":"2020","journal-title":"Cancers"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"35425","DOI":"10.18632\/oncotarget.16019","article-title":"Impact of metformin on C-reactive protein levels in women with polycystic ovary syndrome: a meta-analysis","volume":"8","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"684","DOI":"10.3390\/nu13020684","article-title":"Effects of curcumin on glycemic control and lipid profile in polycystic ovary syndrome: systematic review with meta-analysis and trial sequential analysis","volume":"13","author":"Chien","year":"2021","journal-title":"Nutrients"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1007\/978-1-4684-5101-6_21","article-title":"Progesterone resistance","volume":"196","author":"Chrousos","year":"1986","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1016\/j.fertnstert.2018.08.021","article-title":"Beyond fertility: polycystic ovary syndrome and long-term health","volume":"110","author":"Cooney","year":"2018","journal-title":"Fertil. Steril."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"352","DOI":"10.20945\/2359-3997000000049","article-title":"An update of genetic basis of PCOS pathogenesis","volume":"62","author":"Crespo","year":"2018","journal-title":"Arch. Endocrinol. Metab."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1210\/er.2003-0021","article-title":"Natural killer cells in pregnancy and recurrent pregnancy loss: endocrine and immunologic perspectives","volume":"26","author":"Dosiou","year":"2005","journal-title":"Endocr. Rev."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"160","DOI":"10.3389\/fendo.2019.00160","article-title":"Failure of decidualization and maternal immune tolerance underlies uterovascular resistance in intra uterine growth restriction","volume":"10","author":"Dunk","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1016\/0092-8674(85)90334-4","article-title":"The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling","volume":"40","author":"Ebina","year":"1985","journal-title":"Cell"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1007\/s10815-020-02041-9","article-title":"Clinical utility of the endometrial receptivity analysis in women with prior failed transfers","volume":"38","author":"Eisman","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"2717","DOI":"10.1007\/s12325-021-01693-y","article-title":"Fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer: a cochrane systematic review protocol","volume":"38","author":"Fernandez-Montoli","year":"2021","journal-title":"Adv. Ther."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"110610","DOI":"10.1016\/j.mce.2019.110610","article-title":"Prenatally androgenized female rats develop uterine hyperplasia when adult","volume":"499","author":"Ferreira","year":"2020","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"129","DOI":"10.2119\/molmed.2009.00118","article-title":"Changes in the expression of insulin signaling pathway molecules in endometria from polycystic ovary syndrome women with or without hyperinsulinemia","volume":"16","author":"Fornes","year":"2010","journal-title":"Mol. Med."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1677\/joe.0.1290317","article-title":"The ubiquitous polycystic ovary","volume":"129","author":"Franks","year":"1991","journal-title":"J. Endocrinol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1093\/humrep\/deaa015","article-title":"Seminal plasma promotes decidualization of endometrial stromal fibroblasts in vitro from women with and without inflammatory disorders in a manner dependent on interleukin-11 signaling","volume":"35","author":"George","year":"2020","journal-title":"Hum. Reprod."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"728.e2","DOI":"10.1016\/j.fertnstert.2017.12.024","article-title":"Dehydroepiandrosterone enhances decidualization in women of advanced reproductive age","volume":"109","author":"Gibson","year":"2018","journal-title":"Fertil. Steril."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1046\/j.1365-2265.1997.2321049.x","article-title":"Evidence for a primary abnormality of thecal cell steroidogenesis in the polycystic ovary syndrome","volume":"47","author":"Gilling-Smith","year":"1997","journal-title":"Clin. Endocrinol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"2836","DOI":"10.1210\/jc.2012-1259","article-title":"Hyperandrogenism sensitizes leukocytes to hyperglycemia to promote oxidative stress in lean reproductive-age women","volume":"97","author":"Gonz\u00e1lez","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1210\/jc.2011-2366","article-title":"Loss of WT1 expression in the endometrium of infertile PCOS patients: a hyperandrogenic effect?","volume":"97","author":"Gonzalez","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1038\/nrendo.2010.217","article-title":"Polycystic ovary syndrome: etiology, pathogenesis and diagnosis","volume":"7","author":"Goodarzi","year":"2011","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1210\/jc.2018-00820","article-title":"IUGR is associated with marked hyperphosphorylation of decidual and maternal plasma IGFBP-1","volume":"104","author":"Gupta","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/nrm.2017.89","article-title":"Biochemical and cellular properties of insulin receptor signalling","volume":"19","author":"Haeusler","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"8863","DOI":"10.1038\/s41598-021-88346-w","article-title":"Glucose and fatty acid metabolism involved in the protective effect of metformin against ulipristal-induced endometrial changes in rats","volume":"11","author":"Hamza","year":"2021","journal-title":"Sci. Rep."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"705","DOI":"10.3350\/cmh.2020.0166","article-title":"Long non-coding RNAs in liver diseases: focusing on nonalcoholic fatty liver disease, alcohol-related liver disease, and cholestatic liver disease","volume":"26","author":"Han","year":"2020","journal-title":"Clin. Mol. Hepatol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1810","DOI":"10.1016\/S0140-6736(03)13409-5","article-title":"Polycystic ovary syndrome and endometrial carcinoma","volume":"361","author":"Hardiman","year":"2003","journal-title":"Lancet"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1002\/ame2.12002","article-title":"Homeobox genes for embryo implantation: from mouse to human","volume":"1","author":"He","year":"2018","journal-title":"Animal Models Exp. Med."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1210\/jcem-26-11-1267","article-title":"Androstenedione and testosterone in ovarian venous and peripheral plasma during ovariectomy for breast cancer","volume":"26","author":"Horton","year":"1966","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"5536849","DOI":"10.1155\/2021\/5536849","article-title":"Complementary and alternative medicine for the treatment of abnormal endometrial conditions in women with PCOS: a systematic review and meta-analysis of randomized controlled trials","volume":"2021","author":"Hu","year":"2021","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1530\/JOE-18-0086","article-title":"Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats","volume":"237","author":"Hu","year":"2018","journal-title":"J. Endocrinol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"2101","DOI":"10.3390\/molecules26072101","article-title":"\u03b2-sitosterol circumvents obesity induced inflammation and insulin resistance by down-regulating IKK\u03b2\/NF-\u03baB and JNK signaling pathway in adipocytes of type 2 diabetic rats","volume":"26","author":"Jayaraman","year":"2021","journal-title":"Molecules"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"675935","DOI":"10.3389\/fnut.2021.675935","article-title":"Assessing the contribution of relative macrophage frequencies to subcutaneous adipose tissue","volume":"8","author":"Kalafati","year":"2021","journal-title":"Front. Nutr."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"e021860","DOI":"10.1136\/bmjopen-2018-021860","article-title":"Assessing C reactive protein\/albumin ratio as a new biomarker for polycystic ovary syndrome: a case-control study of women from Bahraini medical clinics","volume":"8","author":"Kalyan","year":"2018","journal-title":"BMJ Open"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1002\/j.1460-2075.1990.tb08280.x","article-title":"Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B","volume":"9","author":"Kastner","year":"1990","journal-title":"EMBO J."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1093\/molehr\/7.2.175","article-title":"The NF-kappaB pathway in human endometrium and first trimester decidua","volume":"7","author":"King","year":"2001","journal-title":"Mol. Hum. Reprod."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/0026-0495(72)90090-x","article-title":"Androgen production and metabolism in normal and virilized women","volume":"21","author":"Kirschner","year":"1972","journal-title":"Metabolism"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1186\/s12916-021-01970-1","article-title":"Metabolic signatures of greater body size and their associations with risk of colorectal and endometrial cancers in the European prospective investigation into cancer and nutrition","volume":"19","author":"Kliemann","year":"2021","journal-title":"BMC Med."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"1637","DOI":"10.1007\/s43032-020-00194-7","article-title":"Hyperandrogenic milieu dysregulates the expression of insulin signaling factors and glucose transporters in the endometrium of patients with polycystic ovary syndrome","volume":"27","author":"Lee","year":"2020","journal-title":"Reprod. Sci."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.fertnstert.2017.05.031","article-title":"Endometrial receptivity in the eutopic endometrium of women with endometriosis: it is affected, and let me show you why","volume":"108","author":"Lessey","year":"2017","journal-title":"Fertil. Steril."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/1423-0127-21-2","article-title":"Endometrial progesterone resistance and PCOS","volume":"21","author":"Li","year":"2014","journal-title":"J. Biomed. Sci."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/s12020-021-02761-7","article-title":"Increased testosterone and proinflammatory cytokines in patients with polycystic ovary syndrome correlate with elevated GnRH receptor autoantibody activity assessed by a fluorescence resonance energy transfer-based bioassay","volume":"74","author":"Li","year":"2021","journal-title":"Endocrine"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"38134","DOI":"10.1038\/srep38134","article-title":"Impaired receptivity and decidualization in DHEA-induced PCOS mice","volume":"6","author":"Li","year":"2016","journal-title":"Sci. Rep."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1620\/tjem.243.95","article-title":"A missense variant rs4645843 in TNF-\u03b1 gene is a risk factor of polycystic ovary syndrome in the Uygur population","volume":"243","author":"Li","year":"2017","journal-title":"Tohoku J. Exp. Med."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"685724","DOI":"10.3389\/fimmu.2021.685724","article-title":"The release of peripheral immune inflammatory cytokines promote an inflammatory cascade in PCOS patients via altering the follicular microenvironment","volume":"12","author":"Liu","year":"2021","journal-title":"Front. Immunol."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.fertnstert.2016.05.003","article-title":"Criteria, prevalence, and phenotypes of polycystic ovary syndrome","volume":"106","author":"Lizneva","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.canlet.2018.10.019","article-title":"A20-mediated deubiquitination of ER\u03b1 in the microenvironment of CD163+ macrophages sensitizes endometrial cancer cells to estrogen","volume":"442","author":"Lv","year":"2019","journal-title":"Cancer Lett."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"139946","DOI":"10.1172\/jci.insight.139946","article-title":"Short-term overnutrition induces white adipose tissue insulin resistance through sn-1,2-diacylglycerol\/PKC\u03b5\/insulin receptor Thr1160 phosphorylation","volume":"6","author":"Lyu","year":"2021","journal-title":"JCI Insight"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.ejogrb.2019.12.019","article-title":"Increase in FoxP3, CD56 immune cells and decrease in glands PGRMC1 expression in the endometrium are associated with recurrent miscarriages","volume":"245","author":"Lyzikova","year":"2020","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"5964","DOI":"10.1210\/jcem.86.12.8074","article-title":"Expression of Wilms\u2019 tumor suppressor gene (WT1) in human endometrium: regulation through decidual differentiation","volume":"86","author":"Makrigiannakis","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"537","DOI":"10.5604\/12321966.1226842","article-title":"Cardiovascular system diseases in patients with polycystic ovary syndrome - the role of inflammation process in this pathology and possibility of early diagnosis and prevention","volume":"23","author":"Marciniak","year":"2016","journal-title":"Ann. Agric. Environ. Med."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"5320","DOI":"10.1210\/jc.2010-0603","article-title":"MUC1 as a discriminator between endometrium from fertile and infertile patients with PCOS and endometriosis","volume":"95","author":"Margarit","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"2222","DOI":"10.1016\/j.fertnstert.2010.01.049","article-title":"Reduced percentage of natural killer cells associated with impaired cytokine network in the secretory endometrium of infertile women with polycystic ovary syndrome","volume":"94","author":"Matteo","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1056\/NEJMcp1514916","article-title":"Clinical practice. Polycystic ovary syndrome","volume":"375","author":"McCartney","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1080\/09513590.2020.1730794","article-title":"The polycystic ovary syndrome and gynecological cancer risk","volume":"36","author":"Meczekalski","year":"2020","journal-title":"Gynecol. Endocrinol."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"3386","DOI":"10.1038\/s41467-021-23571-5","article-title":"Endometrial receptivity and implantation require uterine BMP signaling through an ACVR2A-SMAD1\/SMAD5 axis","volume":"12","author":"Monsivais","year":"2021","journal-title":"Nat. Commun."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"368543","DOI":"10.1155\/2013\/368543","article-title":"Obesity and the endometrium: adipocyte-secreted proinflammatory TNF \u03b1 cytokine enhances the proliferation of human endometrial glandular cells","volume":"2013","author":"Nair","year":"2013","journal-title":"Obstet. Gynecol. Int."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1210\/mend.13.6.0311","article-title":"Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries","volume":"13","author":"Nelson","year":"1999","journal-title":"Mol. Endocrinol."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/s12958-021-00765-6","article-title":"Metformin reduces androgen receptor and upregulates homeobox A10 expression in uterine endometrium in women with polycystic ovary syndrome","volume":"19","author":"Ohara","year":"2021","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1159\/000076691","article-title":"Indices of oxidative stress in eutopic and ectopic endometria of women with endometriosis","volume":"57","author":"Oner-Iyido\u011fan","year":"2004","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1007\/s43032-019-00026-3","article-title":"Pro-inflammatory markers negatively regulate IRS1 in endometrial cells and endometrium from women with obesity and PCOS","volume":"27","author":"Or\u00f3stica","year":"2020","journal-title":"Reprod. Sci."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"4640","DOI":"10.1073\/pnas.051042298","article-title":"A phosphatidylinositol 3-kinase\/Akt\/mTOR pathway mediates and PTEN antagonizes tumor necrosis factor inhibition of insulin signaling through insulin receptor substrate-1","volume":"98","author":"Ozes","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"6276187","DOI":"10.1155\/2020\/6276187","article-title":"From prediabetes to type 2 diabetes mellitus in women with polycystic ovary syndrome: lifestyle and pharmacological management","volume":"2020","author":"Pani","year":"2020","journal-title":"Int. J. Endocrinol."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.jsbmb.2018.04.008","article-title":"Polycystic ovary syndrome (PCOS), an inflammatory, systemic, lifestyle endocrinopathy","volume":"182","author":"Patel","year":"2018","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1111\/aogs.13156","article-title":"Progesterone resistance in endometriosis: origins, consequences and interventions","volume":"96","author":"Patel","year":"2017","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1210\/me.2015-1142","article-title":"Uterine epithelial estrogen receptor-\u03b1 controls decidualization via a paracrine mechanism","volume":"29","author":"Pawar","year":"2015","journal-title":"Mol. Endocrinol."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.bpobgyn.2016.03.008","article-title":"Polycystic ovary syndrome: endometrial markers","volume":"37","author":"Piltonen","year":"2016","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"3765","DOI":"10.1210\/jc.2013-1923","article-title":"Mesenchymal stem\/progenitors and other endometrial cell types from women with polycystic ovary syndrome (PCOS) display inflammatory and oncogenic potential","volume":"98","author":"Piltonen","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1093\/humrep\/dev055","article-title":"Endometrial stromal fibroblasts from women with polycystic ovary syndrome have impaired progesterone-mediated decidualization, aberrant cytokine profiles and promote enhanced immune cell migration in vitro","volume":"30","author":"Piltonen","year":"2015","journal-title":"Hum. Reprod."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jri.2018.08.003","article-title":"Killer-cell immunoglobulin-like receptors associated with polycystic ovary syndrome","volume":"130","author":"Sala Elpidio","year":"2018","journal-title":"J. Reprod. Immunol."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1210\/jc.2008-1389","article-title":"Effect of tumor necrosis factor-alpha on estrogen metabolism and endometrial cells: potential physiological and pathological relevance","volume":"94","author":"Salama","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"100937","DOI":"10.1016\/j.molmet.2020.01.001","article-title":"Metabolic dysfunction in polycystic ovary syndrome: pathogenic role of androgen excess and potential therapeutic strategies","volume":"35","author":"Sanchez-Garrido","year":"2020","journal-title":"Mol. Metab."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.1210\/jc.2010-2600","article-title":"Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles","volume":"96","author":"Savaris","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"5812","DOI":"10.3390\/ijms22115812","article-title":"Role of receptor protein tyrosine phosphatases (RPTPs) in insulin signaling and secretion","volume":"22","author":"Sevillano","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.jpag.2009.07.002","article-title":"Endometrial thickness, uterine, and ovarian ultrasonographic features in adolescents with polycystic ovarian syndrome","volume":"23","author":"Shah","year":"2010","journal-title":"J. Pediatr. Adolesc. Gynecol."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"273","DOI":"10.3390\/biomedicines9030273","article-title":"Getting to know endometriosis-related infertility better: a review on how endometriosis affects oocyte quality and embryo development","volume":"9","author":"Simopoulou","year":"2021","journal-title":"Biomedicine"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2147\/CLEP.S37559","article-title":"Epidemiology, diagnosis, and management of polycystic ovary syndrome","volume":"6","author":"Sirmans","year":"2013","journal-title":"Clin. Epidemiol."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"653627","DOI":"10.3389\/fendo.2021.653627","article-title":"Insulin-like growth factor pathway and the thyroid","volume":"12","author":"Smith","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"103419","DOI":"10.1016\/j.critrevonc.2021.103419","article-title":"C-reactive protein as a diagnostic and prognostic factor of endometrial cancer","volume":"164","author":"Socha","year":"2021","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"e38869","DOI":"10.7554\/eLife.38869","article-title":"Reciprocal regulation among TRPV1 channels and phosphoinositide 3-kinase in response to nerve growth factor","volume":"7","author":"Stratiievska","year":"2018","journal-title":"eLife"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"194","DOI":"10.3390\/jcm10020194","article-title":"Different background: natural killer cell profiles in secondary versus primary recurrent pregnancy loss","volume":"10","author":"Strobel","year":"2021","journal-title":"J. Clin. Med."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"669189","DOI":"10.3389\/fcell.2021.669189","article-title":"Inhibition of Col6a5 improve lipid metabolism disorder in dihydrotestosterone-induced hyperandrogenic mice","volume":"9","author":"Sun","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref92","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1399-0039.2004.00170.x","article-title":"Human uterine leukocytes and pregnancy","volume":"63","author":"Trundley","year":"2004","journal-title":"Tissue Antigens"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1038\/313756a0","article-title":"Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes","volume":"313","author":"Ullrich","year":"1985","journal-title":"Nature"},{"key":"ref94","doi-asserted-by":"publisher","first-page":"e8183","DOI":"10.1097\/MD.0000000000008183","article-title":"Effects of metformin treatment on serum levels of C-reactive protein and interleukin-6 in women with polycystic ovary syndrome: a meta-analysis: a PRISMA-compliant article","volume":"96","author":"Wang","year":"2017","journal-title":"Medicine"},{"key":"ref95","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.1007\/s10552-015-0666-5","article-title":"PTEN expression in benign human endometrial tissue and cancer in relation to endometrial cancer risk factors","volume":"26","author":"Yang","year":"2015","journal-title":"Cancer Causes Control"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s13048-021-00792-2","article-title":"Silencing of lncRNA UCA1 inhibited the pathological progression in PCOS mice through the regulation of PI3K\/AKT signaling pathway","volume":"14","author":"Yang","year":"2021","journal-title":"J. Ovarian Res."},{"key":"ref97","doi-asserted-by":"publisher","first-page":"8973076","DOI":"10.1155\/2019\/8973076","article-title":"Transcriptional regulation of ovarian steroidogenic genes: recent findings obtained from stem cell-derived steroidogenic cells","volume":"2019","author":"Yazawa","year":"2019","journal-title":"Biomed. Res. Int."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1186\/s12885-018-4502-7","article-title":"MIG-6 suppresses endometrial epithelial cell proliferation by inhibiting phospho-AKT","volume":"18","author":"Yoo","year":"2018","journal-title":"BMC Cancer"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.bbrc.2015.04.146","article-title":"Mig-6 regulates endometrial genes involved in cell cycle and progesterone signaling","volume":"462","author":"Yoo","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"493","DOI":"10.3760\/j.issn:0529-567x.2007.07.017","article-title":"Analysis of endometrial pathological status in patients with polycystic ovary syndrome","volume":"42","author":"Zhang","year":"2007","journal-title":"Chin. J. Obstet. Gynecol."},{"key":"ref101","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-021-00641-z","article-title":"An update on the progress of endometrial receptivity in women with polycystic ovary syndrome","author":"Zhao","year":"2021","journal-title":"Reprod. Sci."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.788772\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T01:48:16Z","timestamp":1639705696000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.788772\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,17]]},"references-count":101,"alternative-id":["10.3389\/fphys.2021.788772"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2021.788772","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,17]]},"article-number":"788772"}}