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Increased Expression of KISSI and KISSI Receptor in Human Granulosa Lutein Cells—Potential Pathogenesis of Polycystic Ovary Syndrome

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Abstract

Kisspeptins are a family of neuropeptides that are essential for fertility. Recent experimental data suggest a putative role of kisspeptin signaling in the direct control of ovarian function. To explore the expression of KISS1 and KISS1 receptor (KISS1R) in human granulosa lutein cells and the potential role of KISS1/KISS1R system in the pathogenesis of polycystic ovary syndrome (PCOS), we measured the concentration of KISS1 in follicular fluid, the expression of KISS1 and KISS1R in granulosa lutein cells, and the circulating hormones. The expression levels of KISS1 and KISS1R were significantly upregulated in human granulosa lutein cells obtained from women with PCOS. The expression levels of KISS1 in human granulosa lutein cells highly correlated with those of KISS1R in non-PCOS patients, but not in patients with PCOS, most likely due to the divergent expression patterns in women with PCOS. Additionally, the expression levels of KISS1 highly correlated with the serum levels of anti-Mullerian hormone (AMH). The expression levels of KISS1 and KISS1R, as well as the follicular fluid levels of KISS1, were not significantly different between the pregnant and nonpregnant patients in both PCOS and non-PCOS groups. In conclusion, the increased expression of KISS1 and KISS1R in human granulosa lutein cells may contribute to the pathogenesis of PCOS. The expression levels of KISS1 highly correlated with the serum levels of AMH. The KISS1 and KISS1R system in the ovary may not have a remarkable role in predicting the in vitro fertilization (IVF) outcome.

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References

  1. Roseweir AK, Millar RP. The role of kisspeptin in the control of gonadotrophin secretion. Hum Reprod Update. 2009;15(2): 203–212.

    Article  CAS  Google Scholar 

  2. Pinilla L, Aguilar E, Dieguez C, Millar RP, Tena-Sempere M. Kisspeptins and reproduction: physiological roles and regulatory mechanisms. Physiol Rev. 2012;92(3):1235–1316.

    Article  CAS  Google Scholar 

  3. Skorupskaite K, George JT, Anderson RA. The kisspeptin-GnRH pathway in human reproductive health and disease. Hum Reprod Update. 2014;20(4):485–500.

    Article  CAS  Google Scholar 

  4. Garcia-Ortega J, Pinto FM, Fernandez-Sanchez M, et al. Expression of neurokinin B/NK3 receptor and kisspeptin/KISS1 receptor in human granulosa cells. Hum Reprod. 2014;29(12):2736–2746.

    Article  CAS  Google Scholar 

  5. Peng J, Tang M, Zhang BP, et al. Kisspeptin stimulates progesterone secretion via the Erk1/2 mitogen-activated protein kinase signaling pathway in rat luteal cells. Fertil steril. 2013;99(5): 1436–1443.e1431.

    Article  CAS  Google Scholar 

  6. Hussain MA, Song WJ, Wolfe A. There is kisspeptin - and then there is kisspeptin. Trends Endocrinol Metab. 2015;26(10): 564–572.

    Article  CAS  Google Scholar 

  7. Bhattacharya M, Babwah AV. Kisspeptin: beyond the brain. Endocrinology. 2015;156(4):1218–1227.

    Article  CAS  Google Scholar 

  8. Garcia-Ortega J, Pinto FM, Prados N, et al. Expression of tachy-kinins and tachykinin receptors and interaction with kisspeptin in human granulosa and cumulus cells. Biol Reprod. 2016;94(6): 124.

    Article  Google Scholar 

  9. Merhi Z, Thornton K, Bonney E, Cipolla MJ, Charron MJ, Buyuk E. Ovarian kisspeptin expression is related to age and to monocyte chemoattractant protein-1. J Assist Reprod Genet. 2016;33(4): 535–543.

    Article  Google Scholar 

  10. Laoharatchatathanin T, Terashima R, Yonezawa T, Kurusu S, Kawaminami M. Augmentation of metastin/kisspeptin mRNA expression by the proestrous luteinizing hormone surge in granulosa cells of rats: implications for luteinization. Biol Reprod. 2015;93(1):15.

    Article  Google Scholar 

  11. Cejudo Roman A, Pinto FM, Dorta I, et al. Analysis ofthe expression of neurokinin B, kisspeptin, and their cognate receptors NK3 R and KISS1 R in the human female genital tract. Fertil steril. 2012;97(5):1213–1219.

    Article  CAS  Google Scholar 

  12. Hu K-L, Zhao H, Chang H-M, Yu Y, Qiao J. Kisspeptin/kisspep- tin receptor system in the ovary. Front Endocrinol. 2018;8:365.

    Article  Google Scholar 

  13. Saadeldin IM, Koo OJ, Kang JT, et al. Paradoxical effects of kisspeptin: it enhances oocyte in vitro maturation but has an adverse impact on hatched blastocysts during in vitro culture. Reprod Fertil Dev. 2012;24(5):656–668.

    Article  CAS  Google Scholar 

  14. Gaytan F, Garcia-Galiano D, Dorfman MD, et al. Kisspeptin receptor haplo-insufficiency causes premature ovarian failure despite preserved gonadotropin secretion. Endocrinology. 2014;155(8):3088–3097.

    Article  Google Scholar 

  15. Castellano JM, Gaytan M, Roa J, et al. Expression ofKiSS-1 in rat ovary: putative local regulator of ovulation?. Endocrinology. 2006;147(10):4852–4862.

    Article  CAS  Google Scholar 

  16. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fer-til Steril. 2004;81(1):19–25.

    Article  Google Scholar 

  17. Richards JS, Ascoli M. Endocrine, paracrine, and autocrine signaling pathways that regulate ovulation. Trends Endocrinol Metab. 2018;29(5):313–325.

    Article  CAS  Google Scholar 

  18. Ferrero H, Delgado-Rosas F, Garcia-Pascual CM, et al. Efficiency and purity provided by the existing methods for the isolation of luteinized granulosa cells: a comparative study. Hum Reprod. 2012;27(6):1781–1789.

    Article  CAS  Google Scholar 

  19. Merhi Z, Buyuk E, Berger DS, et al. Leptin suppresses anti-Mullerian hormone gene expression through the JAK2/STAT3 pathway in luteinized granulosa cells of women undergoing IVF. Hum Reprod. 2013;28(6):1661–1669.

    Article  CAS  Google Scholar 

  20. Jeon YE, Lee KE, Jung JA, et al. Kisspeptin, leptin, and retinol-binding protein 4 in women with polycystic ovary syndrome. Gynecol Obstet Inves. 2013;75(4):268–274.

    Article  CAS  Google Scholar 

  21. Chen X, Mo Y, Li L, Chen Y, Li Y, Yang D. Increased plasma metastin levels in adolescent women with polycystic ovary syndrome. Eur J Obstet Gyn R B. 2010;149(1):72–76.

    Article  CAS  Google Scholar 

  22. Yilmaz SA, Kerimoglu OS, Pekin AT, et al. Metastin levels in relation with hormonal and metabolic profile in patients with polycystic ovary syndrome. Eur J Obstet Gyn R B. 2014;180: 56–60.

    Article  CAS  Google Scholar 

  23. Mondal M, Baruah KK, Prakash BS. Determination of plasma kisspeptin concentrations during reproductive cycle and different phases of pregnancy in crossbred cows using bovine specific enzyme immunoassay. Gen Comp Endocrinol. 2015;224: 168–175.

    Article  CAS  Google Scholar 

  24. Mondal M, Karunakaran M, Baruah KK. Development and validation of a sensitive enzymeimmunoassay for determination of plasma metastin in mithun (Bos frontalis). J Immunoass Immu- noch. 2016;37(2):201–216.

    Article  Google Scholar 

  25. Li R, Zhang Q, Yang D, et al. Prevalence of polycystic ovary syndrome in women in China: a large community-based study. Hum Reprod. 2013;28(9):2562–2569.

    Article  Google Scholar 

  26. Kolodziejski PA, Pruszynska-Oszmalek E, Korek E, et al. Serum levels of spexin and kisspeptin negatively correlate with obesity and insulin resistance in women. Physiol Res. 2018;67(1):45–56.

    Article  CAS  Google Scholar 

  27. Panidis D, Rousso D, Koliakos G, et al. Plasma metastinlevels are negatively correlated with insulin resistance and free androgens in women with polycystic ovary syndrome. Fertil Steril. 2006;85(6): 1778–1783.

    Article  CAS  Google Scholar 

  28. Fernandois D, Na E, Cuevas F, Cruz G, Lara HE, Paredes AH. Kisspeptin is involved in ovarian follicular development during aging in rats. J Endocrinol. 2016;228(3):161–170.

    Article  CAS  Google Scholar 

  29. Pineda R, Garcia-Galiano D, Roseweir A, et al. Critical roles of kisspeptins in female puberty and preovulatory gonadotropin surges as revealed by a novel antagonist. Endocrinology. 2010;151(2):722–730.

    Article  CAS  Google Scholar 

  30. Seminara SB, Messager S, Chatzidaki EE, et al. The GPR54 gene as a regulator of puberty. New Engl J Med. 2003;349(17):1614–1627.

    Article  CAS  Google Scholar 

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Acknowledgments

The authors appreciate the help in statistical analysis from Professor Zhao in Peking University Third Hospital.

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Correspondence to Rong Li.

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Hu, KL., Zhao, H., Min, Z. et al. Increased Expression of KISSI and KISSI Receptor in Human Granulosa Lutein Cells—Potential Pathogenesis of Polycystic Ovary Syndrome. Reprod. Sci. 26, 1429–1438 (2019). https://doi.org/10.1177/1933719118818899

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