Proteomics & Glyco-Proteomic Analysis of Follicular Fluid
Information source: University of Cincinnati
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Polycystic Ovary Syndrome; Normal Volunteers
Intervention: IVF Antagonist Protocol (Drug)
Phase: N/A
Status: Not yet recruiting
Sponsored by: University of Cincinnati Official(s) and/or principal investigator(s): Steven Lindheim, MD, MMM, Principal Investigator, Affiliation: University of Cincinnati
Overall contact: Steven Lindheim, MD, MMM, Phone: 513-585-0063, Email: steven.lindheim@uc.edu
Summary
To the best of the investigators knowledge, exhaustive characterization of the low and high
abundant proteins and glyco-proteins of the Follicular Fluid (FF) has not yet been achieved.
Such an analysis may provide critical molecular data on the role of the FF in oocyte
maturation and may identify specific changes in the FF proteome of patients with gynecologic
problems, such as Polycystic Ovary Syndrome (PCOS).
Specific Aims
1. To perform a comprehensive analysis of normal human FF using sensitive mass
spectrometry in combination with conventional approaches for proteomic evaluation and
using HPLC and Western blot for glyco-proteomic analysis.
2. Characterize differential proteomic and glyco-proteomic patterns of the FF in normal
women compared to lean and obese women with PCOS.
3. To supplement the differential proteomic and glyco-proteomic analysis with steroid
hormone analysis in all FF samples.
Clinical Details
Official title: Proteomics & Glyco-Proteomic Analysis of Follicular Fluid Derived From Health Patient/Donors and Polycystic Ovary Syndrome Patients
Study design: Observational Model: Case Control, Time Perspective: Prospective
Primary outcome: Proteomic analysis
Secondary outcome: Hormone analysis
Detailed description:
In this study, we plan to utilize ultrasensitive mass spectrometry (MS) and other
conventional proteomic approaches to identify the low and high abundant proteins present in
human FF. Additionally, we plan to use high-performance liquid chromatography (HPLC) and
Western blot techniques to evaluate the Neu5Gc and glycan array based ELISA techniques to
detect anti-Neu5Gc antibody profile in human FF. This analysis will be performed on FF
samples obtained from normal women undergoing In-Vitro Fertilization and Embryo Transfers
(IVF-ET) for a male factor alone and oocyte donors from our 3rd Party Reproduction Program
and from lean and obese women with PCOS. This study will provide information on protein,
glycoprotein, and steroid hormone expression during normal folliculogenesis and during the
pathologic condition of PCOS, which should also provide basic scientific information on
normal and abnormal oocyte development.
Human FF bathes the developing oocyte. Previous studies indicate that the FF contains
cytokines, steroidal and protein hormones, and growth factors. The presence of proteins with
such significant biological properties implies a paracrine and autocrine role for the FF in
promoting normal oocyte development. Furthermore, the presence of any antigenic sialic acid
Neu5Gc and the presence of antibodies targeting these antigenic glycoconjugates (glycolipid
and glycoproteins decorated with sialic acid) may interfere with oocyte development,
hormonal expression, fertilization, and possibly implantation. Here we hypothesize that an
exhaustive proteomic and glyco-proteomic characterization of human FF is essential for a
thorough understanding of its biological significance. We also hypothesize that PCOS may
have differential expression of the FF protein and glyco-protein milieu, and that the
expression may differ further between lean and obese women with PCOS. PCOS represents a
heterogeneous disorder. The severity of hyperandrogensim, metabolic and menstrual
disturbance, and obesity is variable with up to 40% not clinically expressing signs of
classic hyperandrogenism. On the other hand, these atypical, often lean, PCOS women can have
impaired glucose tolerance and diabetes. Reports suggest that these lean PCOS women have
altered serum IGFBP-1, a characteristic endocrine feature of patients with obese PCOS, and
related to hyperinsulinemia and/or obesity. The lean phenotype of PCOS and its significance
is unclear but may represent a cryptic or unexpressed form of PCOS or may be a prelude to
individuals who will later manifest clinical signs of obese/overweight PCOS. Changes in
expression may be expected because of the different amounts of steroidal hormones and
inflammatory markers in the FF derived from women with PCOS.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Female.
Criteria:
Inclusion criteria: Inclusion Criteria All
1. Female patients undergoing controlled ovarian hyperstimulation (COH), transvaginal
oocyte aspiration (TVA), and Saline Infused Sonography (SIS) with UL collection
2. Age <35 y/o at time of in vitro fertilization (IVF) cycle
3. Normal ovarian function defined Day 3 Follicular Stimulating Hormone (FSH) <8 pg/ml
or Anti-Mullerian Hormone (≥ 1. 0 ng/ml)
Inclusion Criteria Controls:
1. Female patients undergoing COH and TVA donating her oocytes
2. Female patients undergoing COH and TVA for male factor infertility only (i. e. no
female causes of infertility)
3. Normal menstrual cycles
Inclusion Criteria Lean PCOS:
1. Diagnosis of PCOS by Rotterdam Criteria
2. BMI ≤ 25 kg/m2 Inclusion Criteria Classic PCOS
1. Diagnosis of PCOS by Rotterdam Criteria 2. BMI > 30 kg/m2
Exclusion criteria:
1. Age ≥ 35 y/o
2. Female partners with infertility associated diagnosis (i. e. tubal factor, cervical
factor, endometriosis)
3. Unexplained infertility
Locations and Contacts
Steven Lindheim, MD, MMM, Phone: 513-585-0063, Email: steven.lindheim@uc.edu
Center for Reproductive Health, Cincinnati, Ohio 45219, United States; Not yet recruiting Steven Lindheim, MD, MMM, Phone: 513-585-0063, Email: steven.lindheim@uc.edu Julie Sroga, MD, Phone: 513-585-2355, Email: julie.sroga@uc.edu Steven Lindheim, MD,MMM, Principal Investigator
Additional Information
Related publications: Farquhar CM, Birdsall M, Manning P, Mitchell JM, France JT. The prevalence of polycystic ovaries on ultrasound scanning in a population of randomly selected women. Aust N Z J Obstet Gynaecol. 1994 Feb;34(1):67-72. Carmina E, Lobo RA. Do hyperandrogenic women with normal menses have polycystic ovary syndrome? Fertil Steril. 1999 Feb;71(2):319-22. Carmina E, Wong L, Chang L, Paulson RJ, Sauer MV, Stanczyk FZ, Lobo RA. Endocrine abnormalities in ovulatory women with polycystic ovaries on ultrasound. Hum Reprod. 1997 May;12(5):905-9. Clayton RN, Ogden V, Hodgkinson J, Worswick L, Rodin DA, Dyer S, Meade TW. How common are polycystic ovaries in normal women and what is their significance for the fertility of the population? Clin Endocrinol (Oxf). 1992 Aug;37(2):127-34. Mendoza C, Ruiz-Requena E, Ortega E, Cremades N, Martinez F, Bernabeu R, Greco E, Tesarik J. Follicular fluid markers of oocyte developmental potential. Hum Reprod. 2002 Apr;17(4):1017-22. Polson DW, Adams J, Wadsworth J, Franks S. Polycystic ovaries--a common finding in normal women. Lancet. 1988 Apr 16;1(8590):870-2. Suikkari AM, Koivisto VA, Rutanen EM, Yki-Järvinen H, Karonen SL, Seppälä M. Insulin regulates the serum levels of low molecular weight insulin-like growth factor-binding protein. J Clin Endocrinol Metab. 1988 Feb;66(2):266-72. Conover CA, Lee PD, Kanaley JA, Clarkson JT, Jensen MD. Insulin regulation of insulin-like growth factor binding protein-1 in obese and nonobese humans. J Clin Endocrinol Metab. 1992 Jun;74(6):1355-60.
Starting date: December 2011
Last updated: December 5, 2011
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