Ovary Syndrome for Efficient Diagnosis and Targeted Therapy

Understanding the Epigenetic Mechanisms in the Pathophysiology of Polycystic Ovary Syndrome for Efficient Diagnosis and Targeted Therapy

OBJECTIVES:

1. Analysis of DNA methyl transferases (DNMT1, DNMT3A and DNMT3B) and Histone deacetylases (HDAC 1,2,3 and SIRTs) polymorphisms (Somatic and germ line variations).
2. Analysis of differential mRNA and protein expression of epigenetic markers in ovarian tissues obtained from PCOS patients.
3. miRNA regulated epigenetic mechanisms in PCOS
4. Epigenetic regulation of endocrine genes in PCOS

DESIGN : A Case Control study.Sample size:200

1. We will take both blood and ovarian tissue samples used to diagnosis.
2. We will take approximately 3 ml of blood which will be used from the blood sample collected for routine preoperative tests (surgical profile) before their planned surgery or for disease evaluation.
3. Small tissue samples (from ovary) will be taken from the tissue which is surgically excised as a part of treatment.

Inclusion Criteria:

• All the subjects would be of Indian origin (controls ~100, cases ~100). They would be in their reproductive age (18-45 yrs). Rotterdam consensus would be used to diagnose PCOS and cases will be selected based on it.

Criteria for the diagnosis of PCOS would include oligo-ovulation cycles longer than 35 days or less than 26 days, elevated free testosterone levels (0.5 ng/dl; the cutof level for free testosterone level was the mean±2 SD according to normal levels in controls), oligomenorrhea or amenorrhea.

A Ferriman-Gallwey (FG) score of≥7 would be taken as indicator for the presence of hirsutism. In accordance with the above criteria, polycystic ovary morphology would be determined by transvaginal ultrasonography, which defines PCOS as the presence of 12 or more small (2-9 mm) follicles in each ovary.

Control subjects would have no signs of menstrual dysfunction and their androgen levels should be within the normal range, with normal glucose tolerance, and no family history of hirsutism, type 2 diabetes mellitus, and infertility.

Exclusion Criteria:

• Women with other causes of hyperandrogenism such as hyperprolactinemia, androgen-secreting tumors, Cushing syndrome and nonclassic congenital hyperplasia would be excluded from this study.