Skip to main content
Top
Published in: Journal of Translational Medicine 1/2023

Open Access 01-12-2023 | Insulins | Review

The interplay between androgens and the immune response in polycystic ovary syndrome

Authors: Sania Shabbir, Emaan Khurram, Vedhika Sathya Moorthi, Youssef Tamer Hassan Eissa, Mohammad Azhar Kamal, Alexandra E. Butler

Published in: Journal of Translational Medicine | Issue 1/2023

Login to get access

Abstract

Polycystic ovary syndrome (PCOS) is a metabolic-reproductive-endocrine disorder that, while having a genetic component, is known to have a complex multifactorial etiology. As PCOS is a diagnosis of exclusion, standardized criteria have been developed for its diagnosis. The general consensus is that hyperandrogenism is the primary feature of PCOS and is associated with an array of physiological dysfunctions; excess androgens, for example, have been correlated with cytokine hypersecretion, adipocyte proliferation, and signaling pathway dysregulation. Another key feature of PCOS is insulin resistance, resulting in aberrant glucose and fatty acid metabolism. Additionally, the immune system plays a key role in PCOS. Hyperandrogenism stimulates some immune cells while it inhibits others, thereby disrupting the normal balance of immune cells and creating a state of chronic inflammation. This low-grade inflammation could contribute to infertility since it induces ovarian dysfunction. This dysregulated immune response in PCOS exhibits autoimmunity characteristics that require further investigation. This review paper examines the relationship between androgens and the immune response and how their malfunction contributes to PCOS.
Literature
2.
go back to reference Polycystic ovary syndrome (PCOS). Mayo Clinic. 2020. Polycystic ovary syndrome (PCOS). Mayo Clinic. 2020.
4.
go back to reference The Royal Australian College of general Practitioners. Polycystic ovary syndrome. Australian Family. The Royal Australian College of general Practitioners. Polycystic ovary syndrome. Australian Family.
9.
go back to reference Krishnan A, Muthusami S, Periyasamy L, Stanley JA, Gopalakrishnan V, Ramachandran I. Effect of DHT-induced hyperandrogenism on the pro-inflammatory cytokines in a rat model of polycystic ovary morphology. Medicina (Kaunas). 2020;56(3):100.CrossRefPubMed Krishnan A, Muthusami S, Periyasamy L, Stanley JA, Gopalakrishnan V, Ramachandran I. Effect of DHT-induced hyperandrogenism on the pro-inflammatory cytokines in a rat model of polycystic ovary morphology. Medicina (Kaunas). 2020;56(3):100.CrossRefPubMed
11.
go back to reference Zafari Zangeneh F, Naghizadeh MM, Masoumi M. Polycystic ovary syndrome and circulating inflammatory markers. Int J Reprod Biomed (Yazd). 2017;15(6):375–82.CrossRef Zafari Zangeneh F, Naghizadeh MM, Masoumi M. Polycystic ovary syndrome and circulating inflammatory markers. Int J Reprod Biomed (Yazd). 2017;15(6):375–82.CrossRef
12.
go back to reference Bhati M, Prabhu Y, Renu K, Vellingiri B, Thiagarajan P, Panda A, et al. Role of TGF-β signalling in PCOS associated focal segmental glomerulosclerosis. Clin Chim Acta. 2020;510:244–51.CrossRefPubMed Bhati M, Prabhu Y, Renu K, Vellingiri B, Thiagarajan P, Panda A, et al. Role of TGF-β signalling in PCOS associated focal segmental glomerulosclerosis. Clin Chim Acta. 2020;510:244–51.CrossRefPubMed
13.
go back to reference Zhang H-Y, Zhang Y-F, Han Y-K, Xue F-X, Zhao X-H, Zhang X-L. Activation and significance of the PI3K/Akt pathway in endometrium with polycystic ovary syndrome patients. Zhonghua Fu Chan Ke Za Zhi. 2012;47(1):19–23.PubMed Zhang H-Y, Zhang Y-F, Han Y-K, Xue F-X, Zhao X-H, Zhang X-L. Activation and significance of the PI3K/Akt pathway in endometrium with polycystic ovary syndrome patients. Zhonghua Fu Chan Ke Za Zhi. 2012;47(1):19–23.PubMed
14.
go back to reference Ye W, Xie T, Song Y, Zhou L. The role of androgen and its related signals in PCOS. J Cell Mol Med. 2021;25(4):1825–37.CrossRefPubMed Ye W, Xie T, Song Y, Zhou L. The role of androgen and its related signals in PCOS. J Cell Mol Med. 2021;25(4):1825–37.CrossRefPubMed
15.
go back to reference Connolly A, Leblanc S, Baillargeon J-P. Role of lipotoxicity and contribution of the renin-angiotensin system in the development of polycystic ovary syndrome. Int J Endocrinol. 2018;2018:1–13.CrossRef Connolly A, Leblanc S, Baillargeon J-P. Role of lipotoxicity and contribution of the renin-angiotensin system in the development of polycystic ovary syndrome. Int J Endocrinol. 2018;2018:1–13.CrossRef
16.
go back to reference de Medeiros S, Barbosa B, Lin Winck Yamamoto A, Winck Yamamoto M, Soutode Medeiros M, Soares Junior J, et al. The interplay between androgens and adipocytes: the foundation of comorbidities of polycystic ovary syndrome. GREM Gynecol Reproduct Endocrinol Metab. 2022;01:02–8. https://doi.org/10.53260/grem.223011.CrossRef de Medeiros S, Barbosa B, Lin Winck Yamamoto A, Winck Yamamoto M, Soutode Medeiros M, Soares Junior J, et al. The interplay between androgens and adipocytes: the foundation of comorbidities of polycystic ovary syndrome. GREM Gynecol Reproduct Endocrinol Metab. 2022;01:02–8. https://​doi.​org/​10.​53260/​grem.​223011.CrossRef
23.
go back to reference Cassidy-Vu L, Joe E, Kirk JK. Role of statin drugs for polycystic ovary syndrome. J Family Reprod Health. 2016;10(4):165–75.PubMedPubMedCentral Cassidy-Vu L, Joe E, Kirk JK. Role of statin drugs for polycystic ovary syndrome. J Family Reprod Health. 2016;10(4):165–75.PubMedPubMedCentral
25.
go back to reference Figueroa F, Motta A, Acosta M, Mohamed F, Oliveros L, Forneris M. Role of macrophage secretions on rat polycystic ovary: its effect on apoptosis. J Reprod Fertil. 2015;150(5):437–48.CrossRef Figueroa F, Motta A, Acosta M, Mohamed F, Oliveros L, Forneris M. Role of macrophage secretions on rat polycystic ovary: its effect on apoptosis. J Reprod Fertil. 2015;150(5):437–48.CrossRef
26.
30.
go back to reference Wu R, Fujii S, Ryan NK, Van der Hoek KH, Jasper MJ, Sini I, et al. Ovarian leukocyte distribution and cytokine/chemokine mRNA expression in follicular fluid cells in women with polycystic ovary syndrome. Hum Reprod. 2007;22(2):527–35.CrossRefPubMed Wu R, Fujii S, Ryan NK, Van der Hoek KH, Jasper MJ, Sini I, et al. Ovarian leukocyte distribution and cytokine/chemokine mRNA expression in follicular fluid cells in women with polycystic ovary syndrome. Hum Reprod. 2007;22(2):527–35.CrossRefPubMed
32.
go back to reference Gallinelli A, Ciaccio I, Giannella L, Salvatori M, Marsella T, Volpe A. Correlations between concentrations of interleukin-12 and interleukin-13 and lymphocyte subsets in the follicular fluid of women with and without polycystic ovary syndrome. Fertil Steril. 2003;79(6):1365–72.CrossRefPubMed Gallinelli A, Ciaccio I, Giannella L, Salvatori M, Marsella T, Volpe A. Correlations between concentrations of interleukin-12 and interleukin-13 and lymphocyte subsets in the follicular fluid of women with and without polycystic ovary syndrome. Fertil Steril. 2003;79(6):1365–72.CrossRefPubMed
34.
go back to reference Popovic M, Schiffer L, Taylor AE, Arlt W, Vogt D, De GC, et al. Effect of IL-1 receptor antagonism on hyperandrogenemia in women with polycystic ovary syndrome. Endocr abstr. 2021;73:34. Popovic M, Schiffer L, Taylor AE, Arlt W, Vogt D, De GC, et al. Effect of IL-1 receptor antagonism on hyperandrogenemia in women with polycystic ovary syndrome. Endocr abstr. 2021;73:34.
35.
go back to reference Borthakur A, Prabhu Y, Valsala GA. Role of IL-6 signalling in Polycystic Ovarian Syndrome associated inflammation. J Reprod Immunol. 2020;141:103155.CrossRefPubMed Borthakur A, Prabhu Y, Valsala GA. Role of IL-6 signalling in Polycystic Ovarian Syndrome associated inflammation. J Reprod Immunol. 2020;141:103155.CrossRefPubMed
43.
go back to reference Qi X, Yun C, Liao B, Qiao J, Pang Y. The therapeutic effect of interleukin-22 in high androgen-induced polycystic ovary syndrome. J Endocrinol. 2020;245(2):281–9.CrossRefPubMed Qi X, Yun C, Liao B, Qiao J, Pang Y. The therapeutic effect of interleukin-22 in high androgen-induced polycystic ovary syndrome. J Endocrinol. 2020;245(2):281–9.CrossRefPubMed
52.
go back to reference PI3K-AKT signaling pathway. Creative-diagnostics.com. PI3K-AKT signaling pathway. Creative-diagnostics.com.
53.
go back to reference Esfandyari S, Elkafas H, Chugh RM, Park H, Navarro A, Al-Hendy A. Exosomes as biomarkers for female reproductive diseases diagnosis and therapy. Int J Mol Sci. 2021;22(4):2165.CrossRefPubMedPubMedCentral Esfandyari S, Elkafas H, Chugh RM, Park H, Navarro A, Al-Hendy A. Exosomes as biomarkers for female reproductive diseases diagnosis and therapy. Int J Mol Sci. 2021;22(4):2165.CrossRefPubMedPubMedCentral
54.
go back to reference Aziz E, Elham A, Sara S, Simin S, Solmaz MD, Rovshan K, Mohammad H. Current analytical approaches in diagnosis of melanoma. TrAC Trends Analyt Chem. 2019;116:122–35.CrossRef Aziz E, Elham A, Sara S, Simin S, Solmaz MD, Rovshan K, Mohammad H. Current analytical approaches in diagnosis of melanoma. TrAC Trends Analyt Chem. 2019;116:122–35.CrossRef
55.
go back to reference Jahanbani Y, Shafiee S, Davaran S, Roshangar L, Ahmadian E, Eftekhari A, Dolati S, Yousefi M. Stem cells technology as a platform for generating reproductive system organoids and treatment of infertility-related diseases. Cell Biol Int. 2022;46(4):512–22. https://doi.org/10.1002/cbin.11747. (Epub 2021 Dec 30 PMID: 34918417).CrossRefPubMed Jahanbani Y, Shafiee S, Davaran S, Roshangar L, Ahmadian E, Eftekhari A, Dolati S, Yousefi M. Stem cells technology as a platform for generating reproductive system organoids and treatment of infertility-related diseases. Cell Biol Int. 2022;46(4):512–22. https://​doi.​org/​10.​1002/​cbin.​11747. (Epub 2021 Dec 30 PMID: 34918417).CrossRefPubMed
57.
go back to reference Castoria G, Lombardi M, Barone MV, Bilancio A, Di Domenico M, De Falco A, et al. Rapid signalling pathway activation by androgens in epithelial and stromal cells. Steroids. 2004;69(8–9):517–22.CrossRefPubMed Castoria G, Lombardi M, Barone MV, Bilancio A, Di Domenico M, De Falco A, et al. Rapid signalling pathway activation by androgens in epithelial and stromal cells. Steroids. 2004;69(8–9):517–22.CrossRefPubMed
58.
go back to reference Walters KA. Role of androgens in normal and pathological ovarian function. J Reprod Fertil. 2015;149(4):R193-218.CrossRef Walters KA. Role of androgens in normal and pathological ovarian function. J Reprod Fertil. 2015;149(4):R193-218.CrossRef
59.
go back to reference Plotnikov A, Zehorai E, Procaccia S, Seger R. The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation. Biochim Biophys Acta. 2011;1813(9):1619–33.CrossRefPubMed Plotnikov A, Zehorai E, Procaccia S, Seger R. The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation. Biochim Biophys Acta. 2011;1813(9):1619–33.CrossRefPubMed
66.
go back to reference Ashraf S, Nabi M, Rasool SA, Rashid F, Amin S. Hyperandrogenism in polycystic ovarian syndrome and role of CYP gene variants: a review. Egypt J Med Hum Genet. 2019;20(1):1–10.CrossRef Ashraf S, Nabi M, Rasool SA, Rashid F, Amin S. Hyperandrogenism in polycystic ovarian syndrome and role of CYP gene variants: a review. Egypt J Med Hum Genet. 2019;20(1):1–10.CrossRef
71.
go back to reference Banerjee U, Dasgupta A, Khan A, Ghosh MK, Roy P, Rout JK, et al. A cross-sectional study to assess any possible linkage of C/T polymorphism in CYP17a1 gene with insulin resistance in non-obese women with polycystic ovarian syndrome. Indian J Med Res. 2016;143(6):739–47.CrossRefPubMedPubMedCentral Banerjee U, Dasgupta A, Khan A, Ghosh MK, Roy P, Rout JK, et al. A cross-sectional study to assess any possible linkage of C/T polymorphism in CYP17a1 gene with insulin resistance in non-obese women with polycystic ovarian syndrome. Indian J Med Res. 2016;143(6):739–47.CrossRefPubMedPubMedCentral
77.
go back to reference Genazzani A, Prati A, Genazzani A, Battipaglia C, Simoncini T, Szeliga A, et al. Synergistic effects of the integrative administration of acetyl-L-carnitine, L-carnitine, L-arginine and N-acetyl-cysteine on metabolic dynamics and on hepatic insulin extraction in overweight/obese patients with PCOS, GREM Gynecological and Reproductive. Endocrinol Metab. 2020;01(2020):56–63. https://doi.org/10.53260/grem.2010110.CrossRef Genazzani A, Prati A, Genazzani A, Battipaglia C, Simoncini T, Szeliga A, et al. Synergistic effects of the integrative administration of acetyl-L-carnitine, L-carnitine, L-arginine and N-acetyl-cysteine on metabolic dynamics and on hepatic insulin extraction in overweight/obese patients with PCOS, GREM Gynecological and Reproductive. Endocrinol Metab. 2020;01(2020):56–63. https://​doi.​org/​10.​53260/​grem.​2010110.CrossRef
79.
go back to reference Barcellos CRG, Rocha MP, Hayashida SAY, Nery M, Marcondes JAM. Prevalence of abnormalities of glucose metabolism in patients with polycystic ovary syndrome. Arq Bras Endocrinol Metabol. 2007;51(4):601–5.CrossRefPubMed Barcellos CRG, Rocha MP, Hayashida SAY, Nery M, Marcondes JAM. Prevalence of abnormalities of glucose metabolism in patients with polycystic ovary syndrome. Arq Bras Endocrinol Metabol. 2007;51(4):601–5.CrossRefPubMed
84.
go back to reference Jamilian M, Samimi M, Mirhosseini N, Afshar Ebrahimi F, Aghadavod E, Talaee R, Jafarnejad S, Hashemi Dizaji S, Asemi Z. The influences of vitamin D and omega-3 co-supplementation on clinical, metabolic and genetic parameters in women with polycystic ovary syndrome. J Affect Disord. 2018;1(238):32–8. https://doi.org/10.1016/j.jad.2018.05.027. (Epub 2018 May 26).CrossRef Jamilian M, Samimi M, Mirhosseini N, Afshar Ebrahimi F, Aghadavod E, Talaee R, Jafarnejad S, Hashemi Dizaji S, Asemi Z. The influences of vitamin D and omega-3 co-supplementation on clinical, metabolic and genetic parameters in women with polycystic ovary syndrome. J Affect Disord. 2018;1(238):32–8. https://​doi.​org/​10.​1016/​j.​jad.​2018.​05.​027. (Epub 2018 May 26).CrossRef
86.
go back to reference Victor VM, Rovira-Llopis S, Bañuls C, Diaz-Morales N, Castelló R, Falcón R, Gómez M, Rocha M, Hernández-Mijares A. Effects of metformin on mitochondrial function of leukocytes from polycystic ovary syndrome patients with insulin resistance. Eur J Endocrinol. 2015;173(5):683–91. https://doi.org/10.1530/EJE-15-0572. (Epub 2015 Aug 28).CrossRefPubMed Victor VM, Rovira-Llopis S, Bañuls C, Diaz-Morales N, Castelló R, Falcón R, Gómez M, Rocha M, Hernández-Mijares A. Effects of metformin on mitochondrial function of leukocytes from polycystic ovary syndrome patients with insulin resistance. Eur J Endocrinol. 2015;173(5):683–91. https://​doi.​org/​10.​1530/​EJE-15-0572. (Epub 2015 Aug 28).CrossRefPubMed
89.
go back to reference Sadeghi M, Alaee S, Bagheri MJ, Bahmanpoor S. Role of Essential Oil of Mentha Spicata (Spearmint) in Addressing Reverse Hormonal and Folliculogenesis Disturbances in a Polycystic Ovarian Syndrome in a Rat Model. Adv Pharm Bull. 2017;7(4):651–4. https://doi.org/10.15171/apb.2017.078. (Epub 2017 Dec 31).CrossRef Sadeghi M, Alaee S, Bagheri MJ, Bahmanpoor S. Role of Essential Oil of Mentha Spicata (Spearmint) in Addressing Reverse Hormonal and Folliculogenesis Disturbances in a Polycystic Ovarian Syndrome in a Rat Model. Adv Pharm Bull. 2017;7(4):651–4. https://​doi.​org/​10.​15171/​apb.​2017.​078. (Epub 2017 Dec 31).CrossRef
91.
go back to reference Ali A. Polycystic ovary syndrome as an autoimmune disease: a new concept. Obstet Gynecol. 2000;95(6):S48. Ali A. Polycystic ovary syndrome as an autoimmune disease: a new concept. Obstet Gynecol. 2000;95(6):S48.
Metadata
Title
The interplay between androgens and the immune response in polycystic ovary syndrome
Authors
Sania Shabbir
Emaan Khurram
Vedhika Sathya Moorthi
Youssef Tamer Hassan Eissa
Mohammad Azhar Kamal
Alexandra E. Butler
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2023
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-023-04116-4

Other articles of this Issue 1/2023

Journal of Translational Medicine 1/2023 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.