The Apolipoprotein A-I Level Is Downregulated in the Granulosa Cells of Patients with Polycystic Ovary Syndrome and Affects Steroidogenesis

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder found in women. The etiology of PCOS is still not clear, and there are no available studies on the proteome analysis of granulosa cells (GCs) in PCOS patients. To identify the pathogenic mechanisms and potential diagnostic markers for PCOS, we conducted proteomic profiling of GCs in PCOS patients by two-dimensional gel electrophoresis and liquid chromatography coupled with mass spectrometry (LC-MS/MS) analyses. The proteomic analysis yielded eight downregulated and 12 upregulated proteins in PCOS patients, among which apolipoprotein A-I (ApoA-I) showed significant downregulation in PCOS patients as confirmed by Western blotting. Knockdown of ApoA-I decreased the number of transcripts of steroidogenic enzymes in a granulosa cell line (KGN), while its overexpression generally increased the level of expression of these enzymes. Furthermore, modulation of the expression level of ApoA-I in the granulosa cells altered progesterone production. Therefore, this study suggests that ApoA-I can be useful as a granulosa cell biomarker of PCOS patients and that downregulated ApoA-I may be related to the disturbed production of steroid hormones in PCOS patients.

Validation of proteomic biomarkers previously found to be differentially expressed in women with Polycystic Ovary Syndrome: a cross-sectional study

“…Previous proteomic biomarker studies in women with PCOS including one from our group have identified several promising new biomarkers from a variety of tissues in women with PCOS [13][14][15][16][17][22][23][24][25][26][27]. However, we could not identify any study in which any of the biomarkers identified had been validated in independent cohorts of women with PCOS.…”

Proteomic Profiling for Identification of Novel Biomarkers Differentially Expressed in Human Ovaries from Polycystic Ovary Syndrome Patients

“…The integration of the huge amount of novel information obtained from proteomics may contribute to the elucidation of cellular modifications, resulting in PCOS. A large number of biomolecules involved in metabolism, androgen biosynthesis, or chronic inflammation pathways have been studied in previous reports [16–19]. These proteins provide vital information about altered molecular functions in PCOS and raise questions concerning their precise role in its pathogenesis.…”

MECHANISMS IN ENDOCRINOLOGY: Proteomic biomarkers of type 2 diabetes mellitus risk in women with polycystic ovary syndrome

“…This is the transporter protein of HDL and its down-regulation in both T2DM and PCOS is associated with the reduction of HDL levels (in combination with the proposed increase in fractional HDL clearance especially in T2DM) (42). The reduced levels of ApoA-I present in the granulosa cells of women with PCOS could affect cholesteryl ester uptake, which, in turn, would be expected to disturb normal steroidogenesis pathways by limiting the initial substrate (18). Both these mechanisms could contribute to the increase in prevalence of cardiovascular and cerebrovascular accidents observed in patients with T2DM and PCOS compared with the rest of the population.…”

“…All relevant studies published since the previous database was published were reviewed. Thirteen papers (16,18,19,20,21,22,23,24,25,26,27,28,29) were identified including four review articles and one study on mice. The review articles and the study on mice (21,26,27,29) were excluded apart from a previous review article from our group in which original data on new biomarkers for PCOS had been published (16).…”

“…A further three studies were abstracts from conference proceedings with no primary proteomic data on PCOS and so they were also excluded (22,23,24). Data from three of the remaining studies could be accessed through direct online links to the files from the search results (18,19,25). No other sources were used to obtain the selected articles.…”