Aalaap Naigaonkar1, Roshan Dadachanji1, Indira Hinduja2, Srabani Mukherjee3. 1. Department of Molecular Endocrinology, National Institute for Research in Reproductive Health, Indian Council of Medical Research, J.M. Street, Parel, Mumbai, Maharashtra, 400012, India. 2. Hinduja IVF Centre, P. D. Hinduja National Hospital and Medical Research Centre, Mahim, Mumbai, Maharashtra, 400016, India. 3. Department of Molecular Endocrinology, National Institute for Research in Reproductive Health, Indian Council of Medical Research, J.M. Street, Parel, Mumbai, Maharashtra, 400012, India. srabanimuk@yahoo.com.
Abstract
BACKGROUND: Women with polycystic ovary syndrome (PCOS) are often infertile and opt for artificial reproductive techniques (ART) to conceive. Disrupted pro-/antioxidant balance in oocyte microenvironment may contribute towards sub-optimal oocyte/embryo quality and poor ART outcome in them. METHODS: Activities/levels of redox markers and their transcript expression were investigated in follicular fluid and granulosa cells respectively, in women with PCOS (n = 71) and controls (n = 50) undergoing in vitro fertilization (IVF). Correlation analysis of redox markers and IVF parameters was performed. RESULTS: Activities of superoxide dismutase, glutathione reductase, glutathione peroxidase, and paraoxonase1 were significantly lower in follicular fluid of PCOS women than in controls. Levels of lipid peroxidation, oxidative protein modification, and oxidized glutathione were higher, whereas those of total antioxidant capacity, total thiols, and reduced glutathione were lower in follicular fluid of PCOS women than in controls. Further, comparison of redox markers based on insulin resistance and BMI status of study participants showed similar trends, indicating that PCOS pathophysiology is a significant contributor to oxidative stress irrespective of insulin resistance and BMI. Transcript levels of antioxidant enzymes were lower in granulosa cells from PCOS women than in controls, and they accorded with their activities in follicular fluid. Moreover, few redox markers showed significant correlations with oocyte/embryo quality and pregnancy outcome. CONCLUSION: Our data indicates disrupted redox homeostasis in follicular environment in PCOS which may negatively influence oocyte/embryo quality. Further, granulosa cells may play crucial role in maintaining follicular redox homeostasis. Glutathione system and paraoxonase1 could be explored further as surrogates for IVF prognosis/outcome.
BACKGROUND: Women with polycystic ovary syndrome (PCOS) are often infertile and opt for artificial reproductive techniques (ART) to conceive. Disrupted pro-/antioxidant balance in oocyte microenvironment may contribute towards sub-optimal oocyte/embryo quality and poor ART outcome in them. METHODS: Activities/levels of redox markers and their transcript expression were investigated in follicular fluid and granulosa cells respectively, in women with PCOS (n = 71) and controls (n = 50) undergoing in vitro fertilization (IVF). Correlation analysis of redox markers and IVF parameters was performed. RESULTS: Activities of superoxide dismutase, glutathione reductase, glutathione peroxidase, and paraoxonase1 were significantly lower in follicular fluid of PCOS women than in controls. Levels of lipid peroxidation, oxidative protein modification, and oxidized glutathione were higher, whereas those of total antioxidant capacity, total thiols, and reduced glutathione were lower in follicular fluid of PCOS women than in controls. Further, comparison of redox markers based on insulin resistance and BMI status of study participants showed similar trends, indicating that PCOS pathophysiology is a significant contributor to oxidative stress irrespective of insulin resistance and BMI. Transcript levels of antioxidant enzymes were lower in granulosa cells from PCOS women than in controls, and they accorded with their activities in follicular fluid. Moreover, few redox markers showed significant correlations with oocyte/embryo quality and pregnancy outcome. CONCLUSION: Our data indicates disrupted redox homeostasis in follicular environment in PCOS which may negatively influence oocyte/embryo quality. Further, granulosa cells may play crucial role in maintaining follicular redox homeostasis. Glutathione system and paraoxonase1 could be explored further as surrogates for IVF prognosis/outcome.
Authors: Ketty Shkolnik; Ari Tadmor; Shifra Ben-Dor; Nava Nevo; Dalia Galiani; Nava Dekel Journal: Proc Natl Acad Sci U S A Date: 2011-01-10 Impact factor: 11.205