Polycystic ovarian syndrome (PCOS) is a complex disorder affecting up to 15–20% of reproductive women. PCOS has recently been investigated using genome-wide association studies revealing important mutations and DNA methylation sites associated with the syndrome. As a clinically highly heterogenous condition, studying the molecular basis of the differential manifestation of PCOS is both meaningful concerning individualized management and important for understanding the biology of PCOS. Using genome-wide DNA methylation data collected from PCOS patients, we performed a powerful region-based analysis to detect differentially methylated regions (DMR) by correlating DNA methylation pattern in a genomic region with the level of each PCOS clinical sub-phenotype. We identified seven significant DMRs on chromosome 19 (12877188-12876846 bp) and chromosome 6 (MHC region) associated with prolactin level, as well as chromosomes 11 and 2 associated with metabolic attributes. Functional annotation linked significant DNA methylation patterns to functional genes (HOOK2, BDNFl, HLA-G, HLA-H, HLA-J, RNF39, etc) of metabolic disorders and immunity or novel associations to serve as targets for validation and replication.
The effects of platinum-based drugs are controlled by genes that are involved in DNA detoxification, including glutathione S-transferase (GST)P1 and GSTM1, which have been associated with increased benefits in the chemotherapeutic treatment of patients with ovarian cancer. The present study assessed the effect of single nucleotide polymorphisms in GST genes on the overall survival (OS) of patients with ovarian serous cystadenocarcinoma that were treated with chemotherapy. A total of 95 patients received treatment with a carboplatin-based or alternative chemotherapy. Polymorphisms in the patients were genotyped using the following methods: Pyrosequencing, to identify GSTP1 Ile105Val; a relative quantification method, to identify the copy number variation in GSTM1; and polymerase chain reaction followed by gel electrophoresis, to identify the null vs. non-null genotypes of GSTM1. The association between genotypes and OS of patients was assessed using Kaplan-Meier survival curves and Cox proportional hazards regression analysis. The OS of patients treated with paclitaxel + carboplatin-based chemotherapy was significantly increased, compared with patients treated with alternative forms of chemotherapy (P=0.035). The OS of patients did not differ significantly between different GSTP1 genotypes (log-rank test, P=0.17). Cox proportional hazards regression analysis revealed that, since the start of the treatment, there was not a significant association between the GSTP1 isoleucine allele and the OS for heterozygous carriers of the isoleucine allele [hazards ratio (HR), 1.78; 95% confidence interval (CI), 0.77-4.12; P=0.18] and no homozygous carriers of the valine allele had been detected (HR, 0.00). There was no significant difference between GSTM1 genotypes, according to Kaplan-Meier survival analysis (log-rank test, P=0.83). Patients that possessed ≤1 copy of GSTM1 exhibited no decrease in OS (HR, 0.96; 95% CI, 0.37-2.51; P=0.94), compared with patients that possessed two copies of GSTM1 (HR, 0.71; 95% CI, 0.22-2.28; P=0.56). Overall, the present results suggest that there are no associations between polymorphisms in the GSTP1 and GSTM1 genes and the OS of patients with ovarian cancer following administration of adjuvant chemotherapy.
It advocates designing the teaching plan of doing experiment without any aid of tools on the basis of behaviorism theory and the compliance with the rules of experimental teaching.So the author takes the operation of liquid transit as an example to discuss the effect of the application of hand exercise in experimental teaching in chemistry.
Background: Dynein, axonemal, heavy chain 1 (DNAH1) gene mutations have been found to be related to primary ciliary dyskinesia (PCD) and the DNAH1 gene is associated with abnormal flagellar morphology in spermatozoa. Infertility is a common condition in women presenting with primary ovarian insufficiency (POI) characterized by hypergonadotropic hypogonadism. The purpose of this study was to explore the clinical significance of genetic diagnostics in several Chinese primary infertile women with atypical POI. Methods: Four atypical POI patients and 100 healthy subjects were recruited, genetic pathogenicityc factors were investigated by whole exome sequencing (WES). Results: WES revealed a homozygous deletion mutation in the DNAH1 gene (NM_015512.5; c.11726_11727delCT, p.Pro3909Argfs*33) in one of the four POI patients. The 31-year-old affected woman presented with a normal menstrual cycle and elevated plasma levels of FSH, around the postmenopausal range, but had a normal antral follicle count and normal anti-Müllerian hormone levels. The patient, after two failed ovulation cycles, became pregnant in the third IVF cycle and delivered a healthy girl at term. Conclusions: The homozygous deletion mutation in the DNAH1 gene suggested that the patient might have a cilia movement disorder of the fallopian tubes, which is a known infertility factor. Moreover, the significantly elevated plasma level of FSH in this patient is likely one of the most important factors leading to her decreased fertility.
The aim of the present study was to evaluate the factors that affect the success rate of gonadotropin-releasing hormone antagonist on in vitro fertilization/intracytoplasmic sperm injection cycles. Multivariate analysis was performed to assess the factors that influence the outcomes, such as oocytes retrieved, and the success of pregnancy. The results showed that E2, P on human chorionic gonadotropin (HCG) day and body mass index (BMI) were positively correlated with the number of oocytes retrieved (P=0.001, P=0.024, P=0.017, respectively). The duration of infertility as well as the luteinizing hormone on HCG day were negatively correlated with the number of oocytes (P=0.048, P=0.002, respectively). The age of the women and P on HCG day were negatively correlated with successful pregnancy (P<0.001, P=0.022). In conclusion, some parameters, such as E2, P, and LH on the HCG day, as well as age and BMI, may affect treatment outcomes.
The genetic basis of fertilization failure after intracytoplasmic sperm injection (ICSI) is largely unknown and the aim of this study is to investigate the genetic causes of fertilization failure in primary infertile women.Six affected women diagnosed with infertility and fertilization failure were recruited. The genetically pathogenic factor of their fertilization failures were investigated by clinical exome sequencing. One hundred healthy controls were verified by Sanger sequencing.Novel compound heterozygous mutations c.625G > T and c.759-2A > G of WEE2 in one affected individual were revealed by clinical exome sequencing. Trios analysis of the mutations represented an autosomal recessive pattern. The nonsense mutation c.625G > T (p.Glu209*) indicated the truncation of the WEE2 protein and c.759-2A > G was predicted to affect the splicing.The novel variants extend the spectrum of WEE2 mutations, which promotes the prognostic value of testing for WEE2 mutations in infertile women with fertilization failure.
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