Hyperandrogenism and Metabolic Syndrome Are Associated With Changes in Serum-Derived microRNAs in Women With Polycystic Ovary Syndrome

Abstract

Polycystic ovary syndrome (PCOS) remains one of the most common endocrine disorder in premenopausal women with an unfavorable metabolic risk profile. Here, we investigate whether biochemical hyperandrogenism, represented by elevated serum free testosterone, resulted in an aberrant circulating microRNA (miRNAs) expression profile and whether miRNAs can identify those PCOS women with metabolic syndrome (MetS). Accordingly, we measured serum levels of miRNAs as well as biochemical markers related to MetS in a case-control study of 42 PCOS patients and 20 Controls. Patients were diagnosed based on the Rotterdam consensus criteria and stratified based on serum free testosterone levels (≥0.034 nmol/l) into either a normoandrogenic (n = 23) or hyperandrogenic (n = 19) PCOS group. Overall, hyperandrogenic PCOS women were more insulin resistant compared to normoandrogenic PCOS women and had a higher prevalence of MetS. A total of 750 different miRNAs were analyzed using TaqMan Low-Density Arrays. Altered levels of seven miRNAs (miR-485-3p, -1290, -21-3p, -139-3p, -361-5p, -572, and -143-3p) were observed in PCOS patients when compared with healthy Controls. Stratification of PCOS women revealed that 20 miRNAs were differentially expressed between the three groups. Elevated serum free testosterone levels, adjusted for age and BMI, were significantly associated with five miRNAs (miR-1290, -20a-5p, -139-3p, -433-3p, and -361-5p). Using binary logistic regression and receiver operating characteristic curves (ROC), a combination panel of three miRNAs (miR-361-5p, -1225-3p, and -34-3p) could correctly identify all of the MetS cases within the PCOS group. This study is the first to report comprehensive miRNA profiling in different subgroups of PCOS women with respect to MetS and suggests that circulating miRNAs might be useful as diagnostic biomarkers of MetS for a different subset of PCOS.

Metformin decreases miR-122, miR-223 and miR-29a in women with polycystic ovary syndrome

“…miRNAs were subsequently analyzed using Human TaqMan low density array (TLDA) cards containing 24 different assays (ThermoFisher Scientific) according to manufacturers’ protocols. The TLDA card was designed to include a total of 21 miRNAs ( 40 , 49 , 62 ) and miRNAs reported in the literature to be associated with metabolic syndrome, insulin resistance or diabetes (Supplementary Table 1, see section on supplementary materials given at the end of this article). In addition to the 21 selected miRNAs, the card contained two spike in controls (ath-miR-159a and cel-miR-39) and one endogenous control (U6).…”

MicroRNAs in amniotic fluid and maternal blood plasma associated with sex determination and early gonad differentiation in cattle

“…Although we have recently reported differences in terms of SOX9 expression during bovine sex determination with respect to the classic mouse model [ 7 ], it is well known that this transcription factor plays an important role in orchestrating testis morphogenesis in many species [ 4 , 5 , 25 , 62–65 ]. Recently, increased levels of circulating miR-485-3p have been reported in polycystic ovary syndrome patients [ 66 ], but its role during the sex determination process has yet to be determined. In line with this, miR-146a-5p, one of the most upregulated miRNAs in MP of heifers carrying a single male embryo, targets SRY, the key gene in the sex determination process.…”

A Preliminary Study on the Characteristics of microRNAs in Ovarian Stroma and Follicles of Chuanzhong Black Goat during Estrus

“…Hence, these miRNAs may play a role in ovarian organogenesis and hormone secretion through oocyte meiosis. Besides, miR-202-5p and miR-485-3p were significantly upregulated in LF; they have been indicated to have a regulatory role in ovarian hormone metabolism and granulosa cell development [ 55 , 56 ]. In zebrafish, knocking out miR-202 impaired the early steps of oogenesis/folliculogenesis and decreased the number of large (i.e., vitellogenic) follicles, ultimately leading to no reproductive success [ 57 ].…”