Archives of Gynecology and Obstetrics

, Volume 299, Issue 1, pp 277–286 | Cite as

Abnormal expressions of ADAMTS-1, ADAMTS-9 and progesterone receptors are associated with lower oocyte maturation in women with polycystic ovary syndrome

  • Sepide GohariTaban
  • Iraj Amiri
  • Sara Soleimani Asl
  • Massoud Saidijam
  • Mahnaz Yavangi
  • Elham Khanlarzadeh
  • Nooshin Mohammadpour
  • Nooshin Shabab
  • Tayebe ArtimaniEmail author
Gynecologic Endocrinology and Reproductive Medicine



ADAMTS-1 and 9 play a crucial role in the ovulation and their altered levels may play a role in the pathogenesis of polycystic ovary syndrome (PCOS). The aim of this study was to assess ADAMTS-1 and 9 expression and their correlation with the oocyte quality and maturity in the cumulus cells (CCs) of PCOS patients and normovulatory women during an IVF procedure.


Expression of ADAMTS-1 and 9 and progesterone receptors (PRs) in the CCs containing MII and germinal vesicle (GV) oocytes of 37 PCOS patients and 37 women with normal ovulatory function who underwent IVF treatment was evaluated using qRT-PCR. Moreover, correlation between ADAMTS-1 and 9 expression and oocyte quality were also investigated.


mRNA expression levels of ADAMTS-1 and ADAMTS-9 were significantly reduced in the women with PCOS compared to the normovulatory women. ADAMTS-1 and ADAMTS-9 mRNA expression levels in the CCs showed a considerable correlation. Lower expression levels of ADAMTS-1 and ADAMTS-9 in PCOS patients were strongly correlated with diminished oocyte maturation. There was a remarkable association between ADAMTS-1 and ADAMTS-9 mRNA expression levels and oocyte quality. PRs (PRA and PRB) were dramatically decreased in PCOS patients when compared with the control group.


The results of the present study indicated that ADAMTS-1 and ADAMTS-9 as well as PRs are downregulated in the human CCs in PCOS patients, which could be associated with impaired oocyte maturation and may result in a lower oocyte recovery and oocyte maturity rates, as well as lower fertilization rate.


ADAMTS-1 ADAMTS-9 PCOS Progesterone receptors Oocyte maturation 



This work was supported by the Research and Technology Deputy of Hamadan University of Medical Sciences (No: 1394.499). We thank the Research Center for Endometrium and Endometriosis and also the Research Center for Molecular Medicine, Hamadan University of Medical Sciences for technical assistance.

Author contributions

SG project development, IA data collection, SSA data management, MS project development and data management, MY data collection, EK data analysis, NM data collection, NS data collection, TA project development, data management and manuscript writing.

Compliance with ethical standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of Hamadan University of Medical Sciences Ethics Committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.


  1. 1.
    Crespo D, Goetz FW, Planas JV (2015) Luteinizing hormone induces ovulation via tumor necrosis factor alpha-dependent increases in prostaglandin F2alpha in a nonmammalian vertebrate. Sci Rep 5:14210. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Baranova NS, Inforzato A, Briggs DC, Tilakaratna V, Enghild JJ, Thakar D, Milner CM, Day AJ, Richter RP (2014) Incorporation of pentraxin 3 into hyaluronan matrices is tightly regulated and promotes matrix cross-linking. J Biol Chem 289(44):30481–30498CrossRefGoogle Scholar
  3. 3.
    Jeppesen JV, Kristensen SG, Nielsen ME, Humaidan P, Dal Canto M, Fadini R, Schmidt KT, Ernst E, Yding Andersen C (2012) LH-receptor gene expression in human granulosa and cumulus cells from antral and preovulatory follicles. J Clin Endocrinol Metab 97(8):E1524–E1531CrossRefGoogle Scholar
  4. 4.
    Li H, Chian R-C (2017) Follicular development and oocyte growth. In: Development of in vitro maturation for human oocytes. Springer, Berlin, pp 3757Google Scholar
  5. 5.
    Demircan K, Cömertoğlu İ, Akyol S, Yiğitoğlu BN, Sarıkaya E (2014) A new biological marker candidate in female reproductive system diseases: Matrix metalloproteinase with thrombospondin motifs (ADAMTS). J Turk German Gynecol Assoc 15(4):250CrossRefGoogle Scholar
  6. 6.
    Corbett S, Morin-Papunen L (2013) The polycystic ovary syndrome and recent human evolution. Mol Cell Endocrinol 373(1–2):39–50CrossRefGoogle Scholar
  7. 7.
    Allahbadia GN, Merchant R (2011) Polycystic ovary syndrome and impact on health. Middle East Fertil Soc J 16(1):19–37CrossRefGoogle Scholar
  8. 8.
    Xiao S, Li Y, Li T, Chen M, Xu Y, Wen Y, Zhou C (2014) Evidence for decreased expression of ADAMTS-1 associated with impaired oocyte quality in PCOS patients. J Clin Endocrinol Metab 99(6):E1015–E1021CrossRefGoogle Scholar
  9. 9.
    Huang X, Hao C, Shen X, Zhang Y, Liu X (2013) RUNX2, GPX3 and PTX3 gene expression profiling in cumulus cells are reflective oocyte/embryo competence and potentially reliable predictors of embryo developmental competence in PCOS patients. Reprod Biol Endocrinol 11(1):109CrossRefGoogle Scholar
  10. 10.
    Mattison DR (2015) Computational methods for reproductive and developmental toxicology. CRC Press, Boca RatonCrossRefGoogle Scholar
  11. 11.
    Robker R, Russell D, Espey LL, Lydon J, O'Malley B, Richards J (2000) Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases. Proc Natl Acad Sci 97(9):4689–4694CrossRefGoogle Scholar
  12. 12.
    Tang H, Liu Y, Li J, Yin Y, Li G, Chen Y, Li S, Zhang Y, Lin H, Liu X, Cheng CH (2016) Gene knockout of nuclear progesterone receptor provides insights into the regulation of ovulation by LH signaling in zebrafish. Sci Rep 6:28545. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Russell DL, Brown HM, Dunning KR (2015) ADAMTS proteases in fertility. Matrix Biol 44:54–63CrossRefGoogle Scholar
  14. 14.
    Peluffo MC, Murphy MJ, Talcott Baughman S, Stouffer RL, Hennebold JD (2011) Systematic analysis of protease gene expression in the rhesus macaque ovulatory follicle: metalloproteinase involvement in follicle rupture. Endocrinology 152(10):3963–3974CrossRefGoogle Scholar
  15. 15.
    Mishra B, Koshi K, Kizaki K, Ushizawa K, Takahashi T, Hosoe M, Sato T, Ito A, Hashizume K (2013) Expression of ADAMTS1 mRNA in bovine endometrium and placenta during gestation. Domest Anim Endocrinol 45(1):43–48CrossRefGoogle Scholar
  16. 16.
    Karakose M, Demircan K, Tutal E, Demirci T, Arslan MS, Sahin M, Celik HT, Kazanci F, Karakaya J, Cakal E, Delibasi T (2016) Clinical significance of ADAMTS1, ADAMTS5, ADAMTS9 aggrecanases and IL-17A, IL-23, IL-33 cytokines in polycystic ovary syndrome. J Endocrinol Investig 39(11):1269–1275. CrossRefGoogle Scholar
  17. 17.
    Tola EN, Koroglu ND, Yalcin SE, Oral HB (2018) The role of serum ADAMTS-1 and aggrecan on polycystic ovary syndrome in adolescents and younger-aged females. Arch Gynecol Obstet 297(2):487–493. CrossRefPubMedGoogle Scholar
  18. 18.
    Group REAsPcw (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 19(1):41–47CrossRefGoogle Scholar
  19. 19.
    Rosewell KL, Al-Alem L, Zakerkish F, McCord L, Akin JW, Chaffin CL, Brännström M, Curry TE (2015) Induction of proteinases in the human preovulatory follicle of the menstrual cycle by human chorionic gonadotropin. Fertil Steril 103(3):826–833CrossRefGoogle Scholar
  20. 20.
    Tsubota K, Kanki M, Noto T, Nakatsuji S, Oishi Y, Matsumoto M, Nakayama H (2015) Altered gene expression profile in ovarian follicle in rats treated with indomethacin and RU486. J Toxicol Sci 40(3):413–425. CrossRefPubMedGoogle Scholar
  21. 21.
    Curry TE Jr (2010) ADAMTS1 and versican: partners in ovulation and fertilization. Biol Reprod 83(4):505–506. CrossRefPubMedGoogle Scholar
  22. 22.
    Yung Y, Maman E, Konopnicki S, Cohen B, Brengauz M, Lojkin I, Dal Canto M, Fadini R, Dor J, Hourvitz A (2010) ADAMTS-1: a new human ovulatory gene and a cumulus marker for fertilization capacity. Mol Cell Endocrinol 328(1–2):104–108CrossRefGoogle Scholar
  23. 23.
    Guzman L, Adriaenssens T, Ortega-Hrepich C, Albuz F, Mateizel I, Devroey P, De Vos M, Smitz J (2012) Human antral follicles %3c 6 mm: a comparison between in vivo maturation and in vitro maturation in non-hCG primed cycles using cumulus cell gene expression. MHR Basic Sci Reprod Med 19(1):7–16CrossRefGoogle Scholar
  24. 24.
    Enomoto H, Nelson CM, Somerville RP, Mielke K, Dixon LJ, Powell K, Apte SS (2010) Cooperation of two ADAMTS metalloproteases in closure of the mouse palate identifies a requirement for versican proteolysis in regulating palatal mesenchyme proliferation. Development (Cambridge, England) 137(23):4029–4038. CrossRefGoogle Scholar
  25. 25.
    Artimani T, Saidijam M, Aflatoonian R, Amiri I, Ashrafi M, Shabab N, Mohammadpour N, Mehdizadeh M (2015) Estrogen and progesterone receptor subtype expression in granulosa cells from women with polycystic ovary syndrome. Gynecol Endocrinol 31(5):379–383CrossRefGoogle Scholar
  26. 26.
    Akison LK, Boden MJ, Kennaway DJ, Russell DL, Robker RL (2014) Progesterone receptor-dependent regulation of genes in the oviducts of female mice. Physiol Genomics 46(16):583–592. CrossRefPubMedGoogle Scholar
  27. 27.
    Robker RL, Akison LK, Russell DL (2009) Control of oocyte release by progesterone receptor-regulated gene expression. Nucl Recept Signal 7:e012. CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Rekawiecki R, Kowalik MK, Kotwica J (2011) Nuclear progesterone receptor isoforms and their functions in the female reproductive tract. Pol J Vet Sci 14(1):149–158CrossRefGoogle Scholar
  29. 29.
    Lima MA, da Silva SV, Freitas VM (2016) Progesterone acts via the progesterone receptor to induce adamts proteases in ovarian cancer cells. J Ovar Res 9:9. CrossRefGoogle Scholar
  30. 30.
    Willis EL, Bridges PJ, Fortune JE (2017) Progesterone receptor and prostaglandins mediate luteinizing hormone-induced changes in messenger RNAs for ADAMTS proteases in theca cells of bovine periovulatory follicles. Mol Reprod Dev 84(1):55–66. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Sepide GohariTaban
    • 1
  • Iraj Amiri
    • 2
  • Sara Soleimani Asl
    • 2
  • Massoud Saidijam
    • 3
  • Mahnaz Yavangi
    • 2
  • Elham Khanlarzadeh
    • 4
  • Nooshin Mohammadpour
    • 2
  • Nooshin Shabab
    • 3
  • Tayebe Artimani
    • 2
    Email author
  1. 1.Anatomy Department, School of MedicineHamadan University of Medical SciencesHamadanIran
  2. 2.Endometrium and Endometriosis Research CenterHamadan University of Medical SciencesHamadanIran
  3. 3.Research Center for Molecular MedicineHamadan University of Medical SciencesHamadanIran
  4. 4.Department of Community MedicineSchool of MedicineHamadanIran

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