Dataset Information

Proteomic profile of follicular fluid from patients with polycystic ovary syndrome (PCOS) submitted to in vitro fertilization (IVF) compared to oocyte donors.

ABSTRACT: OBJECTIVE:The follicular fluid (FF) of women with polycystic ovary syndrome (PCOS) seems to exhibit a profile different from that of fertile women, which may be related to folliculogenesis disruption in PCOS patients. The aim of this study was to evaluate the differentially expressed proteins in the FF of women with PCOS compared to oocyte donors (ODs). METHODS:This screening study included thirteen (13) women who underwent in vitro fertilization (IVF) cycles: seven (7) ODs and six (6) PCOS patients. The patients underwent standard ovarian stimulation, and the FF was analysed using ion trap and time-of-flight liquid chromatography-mass spectrometry (LCMS-IT-TOF). RESULTS:The FF of the patients was matched to 229 proteins, with 61 proteins exclusive to the PCOS group, 123 proteins exclusive to the ODs, and 45 proteins found in both groups. We highlight fetuin-A and vitamin D ligand protein, which were exclusively expressed in the PCOS group; Complement C3 overexpressed in the PCOS group; and 26S protease only expressed in the OD group. The canonical pathways LXR/RXR activation, FXR/RXR activation, prothrombin activation are directly related to the disrupted metabolism and increased inflammatory status found in PCOS patients. CONCLUSIONS:The findings of the differentially expressed proteins and matched pathways are associated with folliculogenesis, indicating it relevance to oocyte quality.

SUBMITTER: Domingues TS

PROVIDER: S-EPMC6798591 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Proteomic profile of follicular fluid from patients with polycystic ovary syndrome (PCOS) submitted to in vitro fertilization (IVF) compared to oocyte donors.

Domingues Thais S TS Bonetti Tatiana Cs TC Pimenta Daniel C DC Mariano Douglas O C DOC Barros Bruna B Aquino Ana Paula AP Motta Eduardo L A ELA

JBRA assisted reproduction 20191014 4

<h4>Objective</h4>The follicular fluid (FF) of women with polycystic ovary syndrome (PCOS) seems to exhibit a profile different from that of fertile women, which may be related to folliculogenesis disruption in PCOS patients. The aim of this study was to evaluate the differentially expressed proteins in the FF of women with PCOS compared to oocyte donors (ODs).<h4>Methods</h4>This screening study included thirteen (13) women who underwent in vitro fertilization (IVF) cycles: seven (7) ODs and si ...[more]

PMID: 31173497

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Project description:<p><b>PCOS</b> is a complex genetic disease reflecting the interplay of susceptibility genes and environmental factors. The cardinal reproductive feature of the syndrome, hyperandrogenemia, appears to play a direct role in the pathogenesis of the associated metabolic abnormalities. Male as well as female first-degree relatives have reproductive and metabolic phenotypes including increased prevalence rates of type 2 diabetes (T2D), metabolic syndrome (MBS) and other risk factors for cardiovascular disease (CVD). Northwestern University (NU) investigators lead a team that has extensive experience in phenotyping PCOS and in the genetic analysis of complex diseases including genome-wide association study (GWAS). Together with an expert group of collaborators from the Hershey Medical Center, and The University of Chicago, we have conducted a GWAS to identify PCOS susceptibility alleles using a large cohort of extensively and consistently phenotyped PCOS cases. Population controls for this study come from the NUgene project described below.</p> <p><b>NUgene project</b>: In 2002, Northwestern committed to the development of a DNA repository to serve as a platform for the identification and validation of genotype-phenotype associations that will impact healthcare. The NUgene Project is a repository with longitudinal medical information from participating patients at affiliated hospitals and outpatient clinics from the Northwestern University Medical Center. Participants' DNA samples are coupled with data from a questionnaire (2 versions were used, 1 before and 1 after February 2006, both are included) and continuously updated data from our Electronic Medical Record (EMR) representing actual clinical care events. Northwestern has a state-of-the art, comprehensive inpatient and outpatient EMR system of over 2 million patients. NUgene has broad access to participant data for all outpatient visits as well as inpatient data via a consolidated data warehouse. NUgene participants consent to distribution and use of their coded DNA samples and data for a broad range of genetic research by third-party investigators.</p>

Project description:Polycystic ovary syndrome (PCOS) was hypothesized to result from functional ovarian hyperandrogenism (FOH) due to dysregulation of androgen secretion in 1989-1995. Subsequent studies have supported and amplified this hypothesis. When defined as otherwise unexplained hyperandrogenic oligoanovulation, two-thirds of PCOS cases have functionally typical FOH, characterized by 17-hydroxyprogesterone hyperresponsiveness to gonadotropin stimulation. Two-thirds of the remaining PCOS have FOH detectable by testosterone elevation after suppression of adrenal androgen production. About 3% of PCOS have a related isolated functional adrenal hyperandrogenism. The remaining PCOS cases are mild and lack evidence of steroid secretory abnormalities; most of these are obese, which we postulate to account for their atypical PCOS. Approximately half of normal women with polycystic ovarian morphology (PCOM) have subclinical FOH-related steroidogenic defects. Theca cells from polycystic ovaries of classic PCOS patients in long-term culture have an intrinsic steroidogenic dysregulation that can account for the steroidogenic abnormalities typical of FOH. These cells overexpress most steroidogenic enzymes, particularly cytochrome P450c17. Overexpression of a protein identified by genome-wide association screening, differentially expressed in normal and neoplastic development 1A.V2, in normal theca cells has reproduced this PCOS phenotype in vitro. A metabolic syndrome of obesity-related and/or intrinsic insulin resistance occurs in about half of PCOS patients, and the compensatory hyperinsulinism has tissue-selective effects, which include aggravation of hyperandrogenism. PCOS seems to arise as a complex trait that results from the interaction of diverse genetic and environmental factors. Heritable factors include PCOM, hyperandrogenemia, insulin resistance, and insulin secretory defects. Environmental factors include prenatal androgen exposure and poor fetal growth, whereas acquired obesity is a major postnatal factor. The variety of pathways involved and lack of a common thread attests to the multifactorial nature and heterogeneity of the syndrome. Further research into the fundamental basis of the disorder will be necessary to optimally correct androgen levels, ovulation, and metabolic homeostasis.

Project description:Polycystic ovary syndrome (PCOS), the most common endocrine disease among premenopausal women, is caused by both genes and environment. We and others previously reported association between single nucleotide polymorphisms (SNPs) in the DENND1A gene and PCOS. We therefore sequenced the DENND1A gene in white patients with PCOS to identify possible alterations that may be implicated in the PCOS pathogenesis. Patients were referred with PCOS and/or hirsutism between 1998 and 2011 (n = 261). PCOS was diagnosed according to the Rotterdam criteria (n = 165). Sequence analysis was performed in 10 patients with PCOS. Additional patients (n = 251) and healthy female controls (n = 248) were included for SNP genotyping. Patients underwent clinical examination including Ferriman-Gallwey score (FG-score), biochemical analyses and transvaginal ultrasound. Mutation analysis was carried out by bidirectional sequencing. SNP genotyping was tested by allelic discrimination in real-time PCR in the additional patients and controls. Sequencing of the DENND1A gene identified eight SNPs; seven were not known to be associated with any diseases. One missense SNP was detected (rs189947178, A/C), potentially altering the structural conformation of the DENND1A protein. SNP genotyping of rs189947178 showed significantly more carriers among patients with PCOS and moderate hirsutism compared to controls. However, due to small sample size and lack of multiple regression analysis supporting an association between rs189947178 and FG-score or PCOS diagnosis, this could be a false positive finding. In conclusion, sequence analysis of the DENND1A gene of patients with PCOS did not identify alterations that alone could be responsible for the PCOS pathogenesis, but a missense SNP (rs189947178) was identified in one patient and significantly more carriers of rs189947178 were found among patients with PCOS and moderate hirsutism vs. controls. Additional studies with independent cohort are needed to confirm this due to the small sample size of this study.

Dataset Information

Proteomic profile of follicular fluid from patients with polycystic ovary syndrome (PCOS) submitted to in vitro fertilization (IVF) compared to oocyte donors.

Publications

Proteomic profile of follicular fluid from patients with polycystic ovary syndrome (PCOS) submitted to in vitro fertilization (IVF) compared to oocyte donors.

Similar Datasets

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