Role of Serum miRNAs in the Prediction of Ovarian Hyperstimulation Syndrome in Polycystic Ovarian Syndrome Patients

Background: Though oxidative stress is associated with Polycystic Ovary Syndrome (PCOS), the status of nitric oxide is still unclear. Nitric Oxide (NO) plays pivotal roles in many physiological functions which are compromised in PCOS. Our recent study reveals lowered T-regulatory cells (Tregs) in PCOS, and Treg generation is known to be regulated by NO levels. However concrete evidences are lacking on mechanisms modulating NO levels under PCOS. Methods: This is a retrospective case-control cohort study, comprised of PCOS women (N=29) and normal menstruating women as controls (N=20). We analysed NOx (nitrite+nitrate) and hydrogen peroxide (H₂O₂) concentrations, transcript levels of endothelial nitric oxide synthase (eNOS)/inducible nitric oxide synthase (iNOS) and arginine modulators, hydrogen peroxide regulators in the cohort. Results: PCOS women showed reduced plasma NOx(nitrate+nitrite) and H₂O₂ compared to controls. We report reduction in transcript levels of iNOS/NOS2 and eNOS/NOS3 in PCOS peripheral blood. The transcripts involved in arginine bioavailability: Argininosuccinate lyase (ASL), Solute Carrier Family1, member 7 (SLC7A1) and Arginase 1 (ARG1) and Asymmetric Dimethyl Arginine (ADMA) metabolism: Protein arginine methyltransferase 1 (PRMT1) and Dimethylarginine dimethylaminohydrolase 2 (DDAH2) also showed differential expression. H₂O₂ concentration in PCOS women was also found to be reduced. The reduction can be attributed to increase in catalase levels as a consequence of the body’s effort to alleviate the oxidative burden in the system. Conclusion: Our study advocates that PCOS women have lowered NO due to reduced iNOS/eNOS expression, low H₂O₂, high ADMA synthesis and reduced arginine bioavailability. An in-depth analysis of redox biology of PCOS to open up potential therapeutic strategies is highly recommended.

Section: Introductionmentioning

confidence: 99%

Impaired Arginine Metabolism Coupled to a Defective Redox Conduit Contributes to Low Plasma Nitric Oxide in Polycystic Ovary Syndrome

Krishna

Joseph

Thomas

et al. 2017

“…miR-223 suppresses cardiomyocyte hypertrophy by modulating the expression of its target TNNI3K, a troponin interacting kinase [27]. In a study identifying differentially expressed miRNAs in polycystic ovarian syndrome, miR-223 was found to be downregulated and associated with increased risk of ovarian hyperstimulation syndrome [28]. Exosomes mediates miR-223 could inhibit Platelet-Derived Growth Factor Receptor-Beta (PDGFRβ) expression in Vascular Smooth Muscle cells [29].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-873 is a Potential Serum Biomarker for the Detection of Ectopic Pregnancy

Yan²,

Xu³

et al. 2017

Background: Ectopic pregnancy (EP) refers to the implantation of the zygote outside the uterine cavity. In clinical practice, the diagnosis of EP relies on a combination of ultrasound findings and serum human chorionic gonadotrophin (hCG) measurements. However, the need for serial hCG measurements increases the risk of tubal rupture and death, underscoring the need to identify biomarkers for the early detection of EP. Methods: The serum concentrations of 21 microRNAs (miRNAs) associated with pregnancy or with known placental expression, as well as serum hCG and progesterone levels were analyzed 36 patients with viable intrauterine pregnancy (VIP), 30 patients with spontaneous abortion (SA), and 34 patients with EP using specific assay kits and reverse transcription PCR. The diagnostic performance of the different serum markers for detecting EP was analyzed by ROC curve analysis. Results: Five miRNAs were differentially expressed between the three groups, of which miR-873 and miR-223 were significantly lower in EP than in VIP and SA patients and did not change significantly according to gestational age, and miR-323 was significantly higher in EP than in VIP and SA. As a single marker, miR-873 had the highest sensitivity for detecting EP at 61.76% (at a fixed specificity of 90%). In comparison, the combination of hCG, progesterone and miR-873 had the highest sensitivity for detecting EP at 79.41% (at a fixed specificity of 90%). Conclusion: Although further validation in large-scale prospective studies is necessary, our results suggest that miR-873 could be a valuable noninvasive and stable biomarker for the early detection of EP.

“…In our study, clinical pregnancy was defined as the presence of an intrauterine gestational sac on the trans-vaginal ultrasound examination. We did not measure AMH concentrations [23][24][25].…”

Section: Discussionmentioning

confidence: 99%

High Serum FSH is Associated with Brown Oocyte Formation and a Lower Pregnacy Rate in Human IVF Parctice

Deng²,

Luo³

et al. 2016

Background/Aims: To investigate whether brown zona pellucida (ZP) of oocytes affects the outcome of fertilization, embryo quality and pregnancy rate in in vitro fertilization-embryo transfer (IVF-ET). Methods: Based on the ZP color of their oocytes, a total number of 703 patients dated from 2012 to 2014 were divided into a normal egg group (group A) and a brown oocyte group (group B), with 629 and 74 cases, respectively. Clinical characteristics, gonadotropin (Gn) days, Gn dosage, serum hormone levels on the day of human chorionic gonadotropin (HCG) injection, ZP thickness (ZPT) of the eggs, fertilization rate, rescue intracytoplasmic sperm injection (rICSI) rate, good-quality embryo rate and pregnancy rate were compared between the two groups. Results: No significant differences were found in the duration and the causes of infertility, and their basal level of endocrine hormone before IVF-ET between normal egg group and brown egg group. The level of serum hormone including estradiol, progesterone and luteinizing hormone on the day of HCG injection were again similar. Moreover, there were no differences in number of mature oocytes, oocyte fertilization rates and rICSI rates after IVF between the two groups. However, we observed that the ZPT of brown oocytes (group B) was higher than that of normal oocytes (group A). Moreover, the Gn dosage and FSH levels on the day of HCG injection were significantly higher in group B than in group A and the good-quality embryo rate and pregnancy rate in group B were lower than those in group A. Conclusion: Compared with normal eggs, oocytes with a brown ZP were found to have a higher ZPT, lower embryo quality and lower pregnancy rate, which might be due to a high Gn dosage injection and high serum FSH levels during IVT-ET cycles.