Contribution of labor related gene subtype classification on heterogeneity of polycystic ovary syndrome.

OBJECTIVE: As one of the most common endocrine disorders in women of reproductive age, polycystic ovary syndrome (PCOS) is highly heterogeneous with varied clinical features and diverse gestational complications among individuals. The patients with PCOS have 2-fold higher risk of preterm labor which is associated with substantial infant morbidity and mortality and great socioeconomic cost. The study was designated to identify molecular subtypes and the related hub genes to facilitate the susceptibility assessment of preterm labor in women with PCOS. METHODS: Four mRNA datasets (GSE84958, GSE5090, GSE43264 and GSE98421) were obtained from Gene Expression Omnibus database. Twenty-eight candidate genes related to preterm labor or labor were yielded from the researches and our unpublished data. Then, we utilized unsupervised clustering to identify molecular subtypes in PCOS based on the expression of above candidate genes. Key modules were generated with weighted gene co-expression network analysis R package, and their hub genes were generated with CytoHubba. The probable biological function and mechanism were explored through Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. In addition, STRING and Cytoscape software were used to identify the protein-protein interaction (PPI) network, and the molecular complex detection (MCODE) was used to identify the hub genes. Then the overlapping hub genes were predicted. RESULTS: Two molecular subtypes were found in women with PCOS based on the expression similarity of preterm labor or labor-related genes, in which two modules were highlighted. The key modules and PPI network have five overlapping five hub genes, two of which, GTF2F2 and MYO6 gene, were further confirmed by the comparison between clustering subgroups according to the expression of hub genes. CONCLUSIONS: Distinct PCOS molecular subtypes were identified with preterm labor or labor-related genes, which might uncover the potential mechanism underlying heterogeneity of clinical pregnancy complications in women with PCOS.

The Association Between Polycystic Ovary Syndrome and Metabolic Syndrome in Adolescents: a Systematic Review and Meta-analysis.

The association between polycystic ovary syndrome (PCOS) and metabolic syndrome (MetS) is not widely recognized or properly assessed in adolescents. The aim of this study was to conduct a systematic review and meta-analysis to provide reliable results concerning MetS development in adolescents with PCOS. We searched studies published in PubMed, Medline, and Web of Science from January 2010 to December 2020. The quality of studies was assessed by the Newcastle-Ottawa Scale (NOS), and the data analysis was performed with Stata 14.0. Twelve articles were finally included in the systematic review and meta-analysis. The results suggested that adolescents with PCOS have more than three times the odds of having MetS than controls (OR 3.32, 95% CI [2.14, 5.14]). Obese adolescents with PCOS also had a higher risk of MetS than those with obesity but without PCOS (OR 3.97, 95% CI [1.49, 10.53]). Compared to those without PCOS, systolic blood pressure was higher in adolescents with PCOS (weighted mean difference (WMD) 3.85, 95% CI [1.73, 5.97]), while diastolic blood pressure was higher only in girls with PCOS who had a normal weight (WMD 3.52, 95% CI [1.57, 5.48]). The levels of triglycerides were higher in obese adolescents with PCOS than in those with obesity but without PCOS (WMD 27.84, 95% CI [10.16, 45.51]). PCOS could increase the frequency of MetS by influencing blood pressure and lipid metabolism independent of obesity as early as the adolescent period. Thus, clinicians should perform early interventions in adolescents with PCOS and follow up the relevant indicators of MetS to decrease the risk of poor long-term prognosis.

Severe intrahepatic cholestasis of pregnancy due to a Sertoli-Leydig cell tumour in a woman with polycystic ovary syndrome: a case report.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a common gestational complication characterized by pruritus and elevated bile acids, usually occurring in the third trimester when the serum estrogen and progesterone levels are highest. Hyperandrogenism during pregnancy is a pathological state that is mostly induced by polycystic ovary syndrome (PCOS) but rarely by concomitant androgen-secreting ovarian tumours. To date, no correlation has been drawn between ICP and hyperandrogenism. CASE PRESENTATION: Here, we present a rare case of early-onset severe ICP in a PCOS patient conceived via in vitro fertilization-embryo transfer, with worsening hirsutism and acne due to high levels of testosterone and dehydroepiandrosterone sulphate, both of which were produced by a fast-growing ovarian Sertoli-Leydig cell tumour. Her serum estradiol was also very high, which was speculated to be converted from the circulating androgens by the placenta. She had preterm premature rupture of membranes and delivered at 30 weeks, followed by a rapid remission of ICP as her serum estradiol dropped. However, the excessive androgens did not retreat until the large ovarian tumour was surgically removed. CONCLUSION: This unusual case highlights the concurrence of original hyperandrogenism and subsequent hyperestrogenism during pregnancy and the resultant confounding manifestations. Obstetricians should be aware of the potential association between androgen excess and ICP via placental aromatization.

Polycystic ovary syndrome in adolescents with obesity.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age with the prevalence from 5% to 15%, and the prevalence of PCOS in adolescents with obesity seems even higher. The weight status is significantly associated with the quality of life in adolescents with PCOS. OBJECTIVE: This review aims to summarize the latest findings of pathogenesis, diagnosis, comorbidity, and management in PCOS adolescents with obesity. METHODS: This is a narrative review of articles published in PubMed from June 2013 to June 2020 Data were searched using the key words of "polycystic ovary syndrome" AND "adolescent" AND "obesity." RESULTS: Pubertal obesity, particularly central obesity, could have a negative impact on the pathophysiology of PCOS. In adolescents with obesity, a review of medical history and a long-term follow-up for PCOS symptoms are essential to avoid misdiagnosis. There is a link between obesity and comorbidities of PCOS in adolescents. Holistic treatment and concern for related comorbidities should ideally begin as early as possible in obese adolescents once the diagnosis of PCOS is confirmed. CONCLUSION: Adolescents with PCOS and obesity need more attention from physicians and researchers, and the effective interventions in the early stage are critical to improve their life quality.