Decreased expression of ADAMTS-9 and ADAMTS-5 associated with impaired oocyte maturity in PCOS patients

Background: Ovulation is a controlled event that precisely directs oocyte maturation, oocyte selection and rupture and oocyte releasing. More recently, evidence has emerged indicating an important role for members of newly described ADAMTS family of metalloproteinases during the periovulatory interval. PCOS is a common disease with failure in the selection of dominant follicle which results in anovulation. The role of ADAMTS-9 and ADAMTS-5 in the ovulation process is not yet known.Objective: The aim of this study was to investigate changes of ADAMTS-9 and ADAMTS-5 gene expression in cumulus cells of PCOS and their association with progesterone receptors expression and oocyte Maturity.Materials and Methods: After approval of Hamadan University of medical sciences ethics committee and written informed consent of the patient, CCs were isolated from 37 patients with PCOS (according to Rotterdam criteria) and 37 healthy women with normal ovarian function between 2016 and 2017. Purified CCs of patients were separately pooled to form the CCs in GV-stage and CCs in MII-stage groups. After ovarian stimulation with a GnRH agonist, recombinant FSH, and HCG, oocytes were retrieved via ultrasound-guided vaginal puncture. Then CCs were isolated and categorized according to the oocyte nuclear maturation stage: GV or MII (metaphase II stage). Total RNA was extracted and reverse transcription was performed. Gene expression of ADAMTS-9 and ADAMTS-5 was determined by quantitative real-time PCR method (q-PCR). All statistical procedures were run on SPSS 16. p≤0.05 was considered significant.Results: Our data revealed that ADAMTS-9 and ADAMTS-5 express in the human CCs. qRT-PCR demonstrated a decreased expression levels of ADAMTS-9 and ADAMTS-5 in the CCs of PCOS women compared to the healthy women with normal ovarian function (p=0.01 and p=0.007 respectively). Furthermore, we observed increased expression levels of ADAMTS-9 and ADAMTS-5 in the CCs of mature oocytes compared to the GV oocytes (p=0.01 and p=0.001 respectively). Recent studies confirmed a key role for ADAMTS-1 protease as a downstream effector of progesterone receptor function in ovulation. In this study, we observed a significant positive correlation between the expression of progesterone receptor B with ADAMTS-9 and ADAMTS-5 (r=0.4, p=0.0006, and r=0.57, p=0.0001 respectively).Conclusion: ADAMTS-9 and ADAMTS-5 expression in GV oocytes were lower than mature ones. ADAMTS-1 and ADAMTS-9 were upregulated prior to the ovulation in the normal cycling rats and downregulated in PCOS CCs failed to progress through the meiosis. These findings help to further understand PCOS pathology and improve in vitro maturation outcome.

کلیدواژه ها:

ADAMTS-9 ، ADAMTS-5 ، PCOS ، Cumulus cells ، Oocyte Maturity