Multi-omics Analysis of Women With PCOS and Obesity Compared With Non-PCOS Obese Controls

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in reproductive-aged women， which associated with increased risks to develop metabolic disorders, including cardiovascular diseases, diabetes mellitus, and cerebrovascular diseases. The precise pathogenesis of PCOS remains unknown but is thought to be multifactorial, comprising genetic and environmental factors .

Study Overview

• Status: Completed
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Other: No intervention

Detailed Description

To study the pathogenesis of diseases, the study of multi-omics approach has been applied in various diseases researching . Obesity and PCOS are both metabolic disorders, and both have an impact on metagenomics, metabolomics and transcriptome. Currently, multi-omics studies based on obese PCOS are still limited. Therefore, this study tried to use a multi-omics approach that integrates the gut microbiome, serum metabolomics, serum transcriptomics, and clinical indicators to distinguish obese PCOS from obese non-PCOS women. To investigate whether the specific composition of the gut microbiome is associated with PCOS in obese women. Serum metabolomics and transcriptomics were analyzed to explore potential metabolic pathways. Meanwhile, gut microbiome and serum metabolomics are used to predict the occurrence of PCOS. Then, a new metabolite that could predict PCOS were tested on female mice with high fat diet (HFD).

• Study Type: Observational
• Enrollment (Actual): 121

Contacts and Locations

• Study Contact: Name: Manna Zhang, PHD; Phone Number: (86)02066301004; Email: mannazhang@126.com
• Study Contact Backup: Name: Shen Qu, PHD; Phone Number: (86)02066301004; Email: qiliu@tongji.edu.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200070
      • Department of Endocrinology, Shanghai Tenth People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study enrolled 63 PCOS women with obesity and 58 age- and body mass index (BMI)-matched subjects with normal menstrual cycles who were admitted to the Department of Endocrinology, Shanghai Tenth People's Hospital, between April 2019 and November 2022.

Description

Inclusion Criteria:

• patients with obesity (BMI>28kg/m2)
• aged 18-45 years
• Diagnosis of PCOS
• the Rotterdam diagnosis criteria (2003)

Exclusion Criteria:

• Pregnant women;
• Hyperthyroidism or hypothyroidism
• Severe liver and kidney function injury
• Cancer patients;
• Associated with severe infection, severe anemia, neutropenia and other blood system diseases;
• Have type 1 diabetes, single-gene mutated diabetes or other secondary diabetes;
• Patients with mental illness or intellectual disability;
• Have taken drugs for PCOS treatment in the last three months;
• Taking drugs or foods (antibiotics, probiotics, yogurt, etc.) that affect the intestinal flora for nearly one month;
• Have a long history of taking hormone therapy;
• Currently or recently participating in another clinical trial.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Women with PCOS (PCOS group); PCOS women with obesity previously diagnosed with PCOS（meet the 2003 Rotterdam diagnostic criteria） not using hormonal therapy and without other significant health or endocrine issues.	Other: No intervention; No intervention
Women without PCOS (Non-PCOS group); This study enrolled age- and body mass index (BMI)-matched subjects with normal menstrual cycles, not using hormonal therapy, and without any significant health or endocrine issues.	Other: No intervention; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phenotype differences in the Serum non-targeted metabolomics by LC-MS.	Understand phenotypical differences from biological samples comparing women with and without PCOS. Venipuncture blood draws are to be completed and analyzed by a commercial laboratory to comprehensively analyze non-target metabolites.	Samples to be collected once per participant within 7 days of enrollment.
Phenotype differences in the gut microbiome by metagenomic sequencing.	Understand phenotypical differences from biological samples comparing women with and without PCOS. Stool samples are to be collected by women and analyzed with metagenomics sequencing.	Samples to be collected once per participant within 7 days of enrollment
Phenotype differences in the transcriptome expression by mRNA-seq.	Understand phenotypical differences from biological samples comparing women with and without PCOS. The researcher will collect and analyze Venipuncture blood for RNA. Differences in the expression of genes between the two groups of subjects, analysis to select possible pathogenic factors leading to the pathogenesis of PCOS.	Samples to be collected once per participant within 7 days of enrollment.
Phenotype differences in the Serum targeted metabolomics by LC-MS.	Understand phenotypical differences from biological samples comparing women with and without PCOS. Venipuncture blood draws are to be completed and analyzed by a commercial laboratory to comprehensively analyze the target metabolite.	Samples to be collected once per participant within 7 days of enrollment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BMI	Body mass index (BMI)=weight(kg)/height(m)^2.	Samples to be collected once per participant within 7 days of enrollment.
TT	total testosterone in nmol/L.	Samples to be collected once per participant within 7 days of enrollment.
LH	luteinizing hormone in IU/L.	Samples to be collected once per participant within 7 days of enrollment.
FSH	The follicle-stimulating hormone in IU/l.	Samples to be collected once per participant within 7 days of enrollment.
E2	Estradiol in pmol/L.	Samples to be collected once per participant within 7 days of enrollment.
PRL	Prolactin in uIU/ml.	Samples to be collected once per participant within 7 days of enrollment.
HC	Hip Circumference in centimeters.	Samples to be collected once per participant within 7 days of enrollment.
WC	Waist Circumference in centimeters.	Samples to be collected once per participant within 7 days of enrollment.
Waist/hip Ratio	WHR=(Waist Circumference in centimeters)/(Hip Circumference in centimeters).	Samples to be collected once per participant within 7 days of enrollment.
Menstrual cycles	the total number of menstrual periods in the last year.	Samples to be collected once per participant within 7 days of enrollment.
FBG	fasting blood-glucose in mmol/L.	Samples to be collected once per participant within 7 days of enrollment.
PBG	postprandial blood-glucose in mmol/L.	Samples to be collected once per participant within 7 days of enrollment.
FINS	fasting serum insulin in mU/L.	Samples to be collected once per participant within 7 days of enrollment.
PINS	postprandial insulin in mU/L.	Samples to be collected once per participant within 7 days of enrollment.
ALT	alanine aminotransferase in U/L.	Samples to be collected once per participant within 7 days of enrollment.
AST	aspartate aminotransferase in U/L.	Samples to be collected once per participant within 7 days of enrollment.
UA	Uric acid in umol/L.	Samples to be collected once per participant within 7 days of enrollment.
CR	Creatinine in umol/L.	Samples to be collected once per participant within 7 days of enrollment.
Ferriman-Gallwey score	The minimum value of Ferriman-Gallwey score is 0 and the maximum value is 44. An Ferriman-Gallwey score greater than or equal to 6 is considered to be a clinical manifestation of androgen excess.	Samples to be collected once per participant within 7 days of enrollment.
HOMA-IR	Homeostatic model assessment insulin resistance index=FBG*FINS/22.5.	Samples to be collected once per participant within 7 days of enrollment.
HbA1c (%)	glycosylated hemoglobin (%).	Samples to be collected once per participant within 7 days of enrollment.
γ-GT	γ-glutamyl transferase in U/L.	Samples to be collected once per participant within 7 days of enrollment.
BUN	urea nitrogen in mmol/L.	Samples to be collected once per participant within 7 days of enrollment.
SOD	Superoxide dismutase in pg/ml.	Samples to be collected once per participant within 7 days of enrollment.
Interleukin 22, IL-22	Interleukin 22 in pg/ml. The factor reflects that the organism is in an inflammatory state. There is no maximum or minimum value for the factor and the higher scores mean a worse outcome.	Samples to be collected once per participant within 7 days of enrollment.
Interleukin 6，IL-6	Interleukin 6 in pg/ml. The factor reflects that the organism is in an inflammatory state. There is no maximum or minimum value for the factor and the higher scores mean a worse outcome.	Blood samples to be collected once per participant within 7 days of enrollment.
Interleukin 8， IL-8	Interleukin 8 in pg/ml. The factor reflects that the organism is in an inflammatory state. There is no maximum or minimum value for the factor and the higher scores mean a worse outcome.	Blood samples to be collected once per participant within 7 days of enrollment.
Tumor Necrosis Factor， TNF	Tumor Necrosis Factor in pg/ml. The factor reflects that the organism is in an inflammatory state. There is no maximum or minimum value for the factor and the higher scores mean a worse outcome.	Blood samples to be collected once per participant within 7 days of enrollment.
FT	free testosterone in nmol/L.	Blood samples to be collected once per participant within 7 days of enrollment.
DHEAS	Dehydroepiandrosterone Sulfate in ug/dl.	Blood samples to be collected once per participant within 7 days of enrollment.
SHBG	sex hormone-binding globulin in nmol/L.	Blood samples to be collected once per participant within 7 days of enrollment.
AD	Androstenedione in ng/ml.	Blood samples to be collected once per participant within 7 days of enrollment.
LDL-c	low-density lipoprotein cholesterol in mmol/L.	Blood samples to be collected once per participant within 7 days of enrollment.
HDL-c	high-density lipoprotein cholesterol in mmol/L.	Blood samples to be collected once per participant within 7 days of enrollment.
TC	Total Cholesterol in mmol/L.	Blood samples to be collected once per participant within 7 days of enrollment.
TG	Triglyceride in mmol/L.	Blood samples to be collected once per participant within 7 days of enrollment.
CRP	C reactive protein in pg/ml.	Blood samples to be collected once per participant within 7 days of enrollment.

Collaborators and Investigators

• Sponsor: Zhang Manna
• Investigators: Principal Investigator: Manna Zhang, Ph.D, Department of Endocrinology, Shanghai Tenth People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Actual): August 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: May 18, 2022
• First Submitted That Met QC Criteria: July 19, 2022
• First Posted (Actual): July 21, 2022

Study Record Updates

• Last Update Posted (Actual): May 1, 2023
• Last Update Submitted That Met QC Criteria: April 26, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: obesity; Gut microbiome; metabolomics; transcriptomic
• Additional Relevant MeSH Terms: Neoplasms; Endocrine System Diseases; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Polycystic Ovary Syndrome; Obesity
• Other Study ID Numbers: Multi-omics PCOS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No