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IPD6181 |
Delineating pathogenesis of obese and lean PCOS phenotype using integrated transcriptomics and proteomics approach |
Dr. Pallavi Shukla |
This study explores the metabolic and hormonal impact of polycystic ovary syndrome
(PCOS) in women aged 18-39, incorporating plasma protein analysis to deepen
understanding of its biological mechanisms. Patients were recruited from the PCOS Clinic at
the National Institute for Research in Reproductive and Child Health (ICMR-NIRRCH) and
non-PCOS participants from general clinics and...
This study explores the metabolic and hormonal impact of polycystic ovary syndrome
(PCOS) in women aged 18-39, incorporating plasma protein analysis to deepen
understanding of its biological mechanisms. Patients were recruited from the PCOS Clinic at
the National Institute for Research in Reproductive and Child Health (ICMR-NIRRCH) and
non-PCOS participants from general clinics and communities. Blood and plasma samples
were collected for comprehensive biochemical and proteomic profiling. Participants were
categorized into four groups: Obese PCOS (N=33), Lean PCOS (N=11), Obese non-PCOS
(N=12), and Lean non-PCOS (N=25), with diagnoses based on the Rotterdam criteria.
Exclusion criteria ensured chronic diseases, medications, or interfering conditions did not
affect reproductive physiology. A total of 117 women were studied, with 57 diagnosed with
PCOS and 60 serving as controls.
PCOS patients demonstrated higher insulin resistance, as reflected in fasting insulin
levels and HOMA-IR scores. Testosterone levels were elevated across PCOS cases, with lean
PCOS participants exhibiting even higher androgen concentrations. Variations in LH and
FSH ratios further emphasized reproductive hormonal imbalances, while obese PCOS women
had lower sex hormone-binding globulin (SHBG) levels. Lipid profiles revealed elevated
very-low-density lipoprotein (VLDL) cholesterol in PCOS patients, reinforcing concerns
regarding cardiovascular risks. Though total cholesterol and triglyceride levels showed no
clear trend, HDL cholesterol was notably lower in obese PCOS participants.
To understand molecular variations in PCOS, plasma protein quantification and
depletion were performed. A total of 15 samples were pooled into four subgroups for
depletion, following strict protocols using the High Select Top 14 Abundant Protein
Depletion Resin. Plasma samples underwent two rounds of depletion to remove dominant
proteins, such as albumin and immunoglobulins, ensuring accuracy before being sent to IIT-
SAIF for liquid chromatography-mass spectrometry (LC-MS). After depletion, samples were
enzymatically digested and labeled using iTRAQ reagents for multiplex quantification. The
fractions were analyzed using an Orbitrap high-resolution mass spectrometer, generating
MS/MS spectra that mapped peptide identifications back to corresponding proteins. Using
stringent statistical criteria (False Discovery Rate <1%), a distinct list of differentially
expressed proteins (DEPs) was developed. Plasma proteome profiling revealed unique DEPs across four comparative groups:
Obese PCOS vs Obese Control (OP vs OC), Lean PCOS vs Lean Control (LP vs LC), Obese
Control vs Lean Control (OC vs LC), and Obese PCOS vs Lean Control (OP vs LC).
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National Institute for Research in Reproductive Health, Mumbai, Maharashtra, India |
Non targated proteomcis |
2028-12-23 |
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