The therapeutic effect of interleukin-22 in high androgen-induced polycystic ovary syndrome

in Journal of Endocrinology
Authors:
Xinyu Qi Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, China

Search for other papers by Xinyu Qi in
Current site
Google Scholar
PubMed Close
,
Chuyu Yun Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, School of Basic Medical Sciences, Peking University, Beijing, China

Search for other papers by Chuyu Yun in
Current site
Google Scholar
PubMed Close
,
Baoying Liao Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, China
Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China

Search for other papers by Baoying Liao in
Current site
Google Scholar
PubMed Close
,
Jie Qiao Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, China
Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China
National Clinical Research Center for Obstetrics and Gynecology, Beijing, China
Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Beijing, China

Search for other papers by Jie Qiao in
Current site
Google Scholar
PubMed Close
, and
Yanli Pang Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, China
Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China

Search for other papers by Yanli Pang in
Current site
Google Scholar
PubMed Close

Correspondence should be addressed to Y Pang: yanlipang@bjmu.edu.cn
DOI:
https://doi.org/10.1530/JOE-19-0589
Volume/Issue:
Volume 245: Issue 2
Article Type:
Research Article
Page Range:
281–289
Online Publication Date:
May 2020
Copyright:
© 2020 Society for Endocrinology 2020
Restricted access
Rent on DeepDyve

Sign up for journal news

Polycystic ovary syndrome (PCOS) is a complex syndrome involving both endocrine and metabolic disorders. Gut microbiota and the intestinal immune factor IL-22 play an important role in the pathogenesis of PCOS. However, the therapeutic role of IL-22 in high androgen-induced PCOS mice is not clear. We aimed to determine the therapeutic effects of IL-22 on the DHEA-induced PCOS mouse model and to explore the possible mechanism of IL-22 in regulating hyperandrogenism-associated PCOS. Insulin resistance levels and ovarian functions were investigated in DHEA-induced PCOS mice with or without additional IL-22 treatment. We found that IL-22 could reverse insulin resistance, disturbed estrous cycle, abnormal ovary morphology, and decreased embryo number in DHEA mice. Mechanistically, IL-22 upregulated the browning of white adipose tissue in DHEA mice. This study demonstrated that IL-22-associated browning of white adipose tissue regulated insulin sensitivity and ovarian functions in PCOS, suggesting that IL-22 may be of value for the treatment of PCOS with a hyperandrogenism phenotype.

Supplementary Materials

    • Supplementary Table 1. Primer sequences for real-time PCR used in the study.

Journal of Endocrinology is committed to supporting researchers in demonstrating the impact of their articles published in the journal.

The two types of article metrics we measure are (i) more traditional full-text views and pdf downloads, and (ii) Altmetric data, which shows the wider impact of articles in a range of non-traditional sources, such as social media.

More information is on the Reasons to publish page.

Sept 2018 onwards Past Year Past 30 Days
Full Text Views 2575 47 5
PDF Downloads 2529 63 3

 

  • Collapse
  • Expand
Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© 2020 Society for Endocrinology 2020
Page(s):
9
Article Type:
Research Article
Received Date:
05 Mar 2020
Accepted Date:
09 Mar 2020
Print Publication Date:
01 May 2020
Online Publication Date:
May 2020
Keywords:
polycystic ovary syndrome; hyperandrogenism; ovarian function; insulin resistance; IL-22

  • Antunes LC, Elkfury JL, Jornada MN, Foletto KC & Bertoluci MC 2016 Validation of HOMA-IR in a model of insulin-resistance induced by a high-fat diet in Wistar rats. Archives of Endocrinology and Metabolism 60 138–142. (https://doi.org/10.1590/2359-3997000000169)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bartelt A & Heeren J 2014 Adipose tissue browning and metabolic health. Nature Reviews: Endocrinology 10 24–36. (https://doi.org/10.1038/nrendo.2013.204)

  • Brestoff JR & Artis D 2015 Immune regulation of metabolic homeostasis in health and disease. Cell 161 146–160. (https://doi.org/10.1016/j.cell.2015.02.022)

  • Dalmas E & Donath MY 2014 A role for interleukin-22 in the alleviation of metabolic syndrome. Nature Medicine 20 1379–1381. (https://doi.org/10.1038/nm.3748)

  • Dudakov JA, Hanash AM & van den Brink MR 2015 Interleukin-22: immunobiology and pathology. Annual Review of Immunology 33 747–785. (https://doi.org/10.1146/annurev-immunol-032414-112123)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Dumesic DA, Oberfield SE, Stener-Victorin E, Marshall JC, Laven JS & Legro RS 2015 Scientific statement on the diagnostic criteria, epidemiology, pathophysiology, and molecular genetics of polycystic ovary syndrome. Endocrine Reviews 36 487–525. (https://doi.org/10.1210/er.2015-1018)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Fang S, Suh JM, Reilly SM, Yu E, Osborn O, Lackey D, Yoshihara E, Perino A, Jacinto S, Lukasheva Y, et al. 2015 Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nature Medicine 21 159–165. (https://doi.org/10.1038/nm.3760)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Filippou P & Homburg R 2017 Is foetal hyperexposure to androgens a cause of PCOS? Human Reproduction Update 23 421–432. (https://doi.org/10.1093/humupd/dmx013)

  • Lee JS, Cella M, McDonald KG, Garlanda C, Kennedy GD, Nukaya M, Mantovani A, Kopan R, Bradfield CA, Newberry RD, et al. 2011 AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch. Nature Immunology 13 144–151. (https://doi.org/10.1038/ni.2187)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lopez M, Nogueiras R, Tena-Sempere M & Dieguez C 2016 Hypothalamic AMPK: a canonical regulator of whole-body energy balance. Nature Reviews: Endocrinology 12 421–432. (https://doi.org/10.1038/nrendo.2016.67)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Mahesh VB & Greenblatt RB 1962 Isolation of dehydroepiandrosterone and 17alpha-hydroxy-delta5-pregenolone from the polycystic ovaries of the Stein-Leventhal syndrome. Journal of Clinical Endocrinology and Metabolism 22 441–448. (https://doi.org/10.1210/jcem-22-4-441)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Norman RJ, Dewailly D, Legro RS & Hickey TE 2007 Polycystic ovary syndrome. Lancet 370 685–697. (https://doi.org/10.1016/S0140-6736(07)61345-2)

  • Osuka S, Nakanishi N, Murase T, Nakamura T, Goto M, Iwase A & Kikkawa F 2018 Animal models of polycystic ovary syndrome: a review of hormone-induced rodent models focused on hypothalamus-pituitary-ovary axis and neuropeptides. Reproductive Medicine and Biology 18 151–160. (https://doi.org/10.1002/rmb2.12262)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ouyang W & O’Garra A 2019 IL-10 family cytokines IL-10 and IL-22: from basic science to clinical translation. Immunity 50 871–891. (https://doi.org/10.1016/j.immuni.2019.03.020)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ouyang W, Rutz S, Crellin NK, Valdez PA & Hymowitz SG 2011 Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annual Review of Immunology 29 71–109. (https://doi.org/10.1146/annurev-immunol-031210-101312)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Pedersen BK & Febbraio MA 2008 Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiological Reviews 88 1379–1406. (https://doi.org/10.1152/physrev.90100.2007)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Qi X, Zhang B, Zhao Y, Li R, Chang HM, Pang Y & Qiao J 2017 Hyperhomocysteinemia promotes insulin resistance and adipose tissue inflammation in PCOS mice through modulating M2 macrophage polarization via estrogen suppression. Endocrinology 158 1181–1193. (https://doi.org/10.1210/en.2017-00039)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Qi X, Yun C, Sun L, Xia J, Wu Q, Wang Y, Wang L, Zhang Y, Liang X, Wang L, et al. 2019 Gut microbiota-bile acid-interleukin-22 axis orchestrates polycystic ovary syndrome. Nature Medicine 25 1225–1233. (https://doi.org/10.1038/s41591-019-0509-0)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rosenfield RL & Ehrmann DA 2016 The pathogenesis of polycystic ovary syndrome (PCOS): the hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocrine Reviews 37 467–520. (https://doi.org/10.1210/er.2015-1104)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Roy S, Mahesh VB & Greenblatt RB 1962 Effect of dehydroepiandrosterone and delta4-androstenedione on the reproductive organs of female rats: production of cystic changes in the ovary. Nature 196 42–43. (https://doi.org/10.1038/196042a0)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rutz S, Wang X & Ouyang W 2014 The IL-20 subfamily of cytokines – from host defence to tissue homeostasis. Nature Reviews: Immunology 14 783–795. (https://doi.org/10.1038/nri3766)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sabat R & Wolk K 2015 Deciphering the role of interleukin-22 in metabolic alterations. Cell and Bioscience 5 68. (https://doi.org/10.1186/s13578-015-0060-8)

  • Shi D & Vine DF 2012 Animal models of polycystic ovary syndrome: a focused review of rodent models in relationship to clinical phenotypes and cardiometabolic risk. Fertility and Sterility 98 185–193. (https://doi.org/10.1016/j.fertnstert.2012.04.006)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Tata B, Mimouni NEH, Barbotin AL, Malone SA, Loyens A, Pigny P, Dewailly D, Catteau-Jonard S, Sundstrom-Poromaa I, Piltonen TT, et al. 2018 Elevated prenatal anti-Mullerian hormone reprograms the fetus and induces polycystic ovary syndrome in adulthood. Nature Medicine 24 834–846. (https://doi.org/10.1038/s41591-018-0035-5)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • van Houten EL & Visser JA 2014 Mouse models to study polycystic ovary syndrome: a possible link between metabolism and ovarian function? Reproductive Biology 14 32–43. (https://doi.org/10.1016/j.repbio.2013.09.007)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wang X, Ota N, Manzanillo P, Kates L, Zavala-Solorio J, Eidenschenk C, Zhang J, Lesch J, Lee WP, Ross J, et al. 2014 Interleukin-22 alleviates metabolic disorders and restores mucosal immunity in diabetes. Nature 514 237–241. (https://doi.org/10.1038/nature13564)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wang X, Wong K, Ouyang W & Rutz S 2019 Targeting IL-10 family cytokines for the treatment of human diseases. Cold Spring Harbor Perspectives in Biology 11 a028548. (https://doi.org/10.1101/cshperspect.a028548)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wu H & Ballantyne CM 2014 Inflammation versus host defense in obesity. Cell Metabolism 20 708–709. (https://doi.org/10.1016/j.cmet.2014.10.013)

  • Yuan X, Hu T, Zhao H, Huang Y, Ye R, Lin J, Zhang C, Zhang H, Wei G, Zhou H, et al. 2016 Brown adipose tissue transplantation ameliorates polycystic ovary syndrome. PNAS 113 2708–2713. (https://doi.org/10.1073/pnas.1523236113)

    • PubMed
    • Search Google Scholar
    • Export Citation