Zhaolian Wei

Prevalence of polycystic ovary syndrome in women in China: a large community-based study.

STUDY QUESTION What is the prevalence of polycystic ovary syndrome (PCOS) in Han Chinese women from different communities? SUMMARY ANSWER The prevalence of PCOS in Chinese women aged 19-45 years is 5.6%. WHAT IS KNOWN ALREADY The prevalence of PCOS is reported to range from 5 to 10% but to the best of our knowledge the Han Chinese population has not been studied. STUDY DESIGN, SIZE, DURATION A large-scale epidemiological study was carried out between October 2007 and September 2011 in 15 924 Han Chinese women of reproductive age (19-45 years) from the 10 provinces and municipalities in China. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 16 886 women from 152 cities and 112 villages were involved in the study. All study participants received a questionnaire and underwent a physical and transvaginal ultrasound examination. Blood samples were collected from a subsample of women (n = 3565) for analysis of metabolic markers and hormones. Based on the Rotterdam PCOS criteria, we assessed hyperandrogenism (H), chronic anovulation (O) and polycystic ovaries (P). Following diagnosis, women with PCOS were assigned to one of four different phenotypes. Finally, the prevalence and related risks of PCOS among Chinese women were estimated based on all the data sources. MAIN RESULTS AND THE ROLE OF CHANCE A total of 16 886 women were initially involved in the study and 15 924 eligible participants then completed the study; the overall response rate was 94.3% (15 924/16 886). The prevalence of PCOS in the Chinese community population was 5.6% (894/15 924). Blood samples were analyzed from 833 of these women who were assigned to the four PCOS phenotypes as follows: 19% H + O, 37% H + P, 15% O + P and 29% H + O + P. Comparing the 833 women with PCOS to 2732 women without PCOS indicated that PCOS occurs in younger women (P < 0.05) and these women were prone not only to menstrual problems, hyperandrogenism, PCO and infertility but also metabolic syndrome (MS) and insulin resistance (IR). However, there was no significant difference in the rate of hypertension or hyperlipemia between the two groups. Obese patients with PCOS had a higher rate of MS (16 versus 48%), IR (7 versus 28%), hypertension (8 versus 30%) and hyperlipemia (48 versus 73%) compared with non-obese patients (all P < 0.05), respectively. The rates of metabolic complications in patients with PCOS increased with age. LIMITATIONS, REASONS FOR CAUTION Age and ethnic origin contribute to the differing manifestations of PCOS; therefore, sampling is one of the most important issues in epidemiological research into PCOS. Owing to the mobility of the Chinese population, the survey among resident populations caused a certain deviation in the age distribution. WIDER IMPLICATIONS OF THE FINDINGS The prevention and treatment of PCOS, particularly in those who are obese, are essential in Chinese women of reproductive age.

Cryopreservation of immature and in-vitro matured human oocytes by vitrification

The objective of this study was to determine the efficacy of vitrification of human oocytes before and after in-vitro maturation (IVM). The immature oocytes recovered (n = 472) were divided into two groups: (i) immature oocytes (n = 219) vitrified at the germinal vesicle (GV) stage; and (ii) immature GV-stage oocytes (n = 253) that were firstly matured in vitro (MII-stage oocytes; n = 178), then vitrified (n = 79). The remaining oocytes (n = 99), which were not vitrified, were processed as controls. After warming, the oocyte survival, maturation and fertilization rates, as well as embryonic development, were compared. The results showed no significant difference between the survival rates of the oocytes vitrified at GV stage and those vitrified at MII stage (85.4% versus 86.1%). However, oocyte maturation rates were significantly reduced (P < 0.05) when oocytes were vitrified at immature GV stage followed by IVM (50.8%) in comparison with the control group (70.4%). Following insemination by intracytoplasmic sperm injection, there was no difference in the fertilization (62.1% versus 58.8%), cleavage (69.5% versus 67.5%) and blastocyst development (0.0% versus 0.0%) rates between these two groups. However, these results were significantly lower (P < 0.05) than those achieved in the control group. This suggests that better results can be achieved by vitrifying mature oocytes rather than immature oocytes.

A novel mutation of HOXA10 in a Chinese woman with a Müllerian duct anomaly

BACKGROUND Müllerian duct anomalies consist of a set of congenital structural malformations that occur when the Müllerian ducts do not develop properly during embryonic life. Their molecular genetic basis is poorly understood. METHODS In this study, we conducted mutation analysis of the HOXA10 gene in a cohort of 109 Chinese women with Müllerian duct anomalies. RESULTS We identified a novel mutation (Y57C) in one patient with a didelphic uterus. The mutation affected the transcriptional regulation capacity of HOXA10. CONCLUSIONS Our study showed that mutation of HOXA10 gene may contribute to the development of Müllerian duct anomalies and confirmed that HOXA10 is an important transcription factor in reproductive tract development.

Mutational analysis of human bone morphogenetic protein 15 in Chinese women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is one of the common defects that cause ovary dysfunction and link to the aberrant process of folliculogenesis. Bone morphogenetic protein 15 (BMP15) is expressed in human oocytes and functions importantly to regulate early follicle growth and fertility. Previous studies have discovered several mutations in the screening of BMP15 in premature ovarian failure but none in PCOS. In this current study, we focused on the mutational analysis of the coding region of BMP15 among 216 Chinese PCOS patients. Five novel missense mutations in BMP15 were discovered, namely, c.34C>G, c.109G>C, c.169C>G, c.288G>C, and c.598C>T. These results are the first to indicate that BMP15 gene mutations may be potentially associated with PCOS patients.

Spermatogenesis affects the outcome of ICSI for azoospermic patients rather than sperm retrieval method.

The study investigated the clinical outcome of intracytoplasmic sperm injection (ICSI) with epididymal and testicular sperm of azoospermic patients exhibiting various disturbances in spermatogenesis, in order to understand the possible factors that might affect ICSI outcome. Of the 134 patients, 92 were diagnosed as being obstructive azoospermic (OA group) with normal spermatogenesis and the remaining 42 patients were diagnosed as being non-obstructive azoospermic (NOA group) with hypospermatogenesis. The 92 OA patients underwent 112 ICSI cycles, which were divided into two subgroups according to their sperm retrieval methods: 1) OA-PESA group (n=51) with sperm obtained by percutaneous sperm aspiration (PESA) cycles and 2) OA-TEFNA group (n=61) with sperm obtained by testicular fine needle sperm aspiration (TEFNA) cycles. The NOA patients diagnosed with hypospermatogenesis according to histopathological analysis and hormone analysis, underwent 42 ICSI cycles with TEFNA. The results showed that the fertilization, cleavage, and clinical pregnancy rates portrayed a significant difference (44.9% vs. 64.1%, P<0.001, 79.8% vs. 89.0%, P<0.001, and 21.4% vs. 40.2%, P=0.047, respectively) between NOA and OA groups. Moreover, the miscarriage rate in the NOA group was visibly higher even though it did not reach a statistical difference (33.3% vs. 15.6%, P=0.433) compared with the miscarriage rate of the OA group. The same statistical differences were observed between the subgroup OA-TEFNA and the NOA group. No statistical difference was observed between OA-PESA and OA-TEFNA groups for the fertilization, cleavage, clinical pregnancy, and miscarriage rates. This study indicates that defective spermatogenesis affects the ICSI clinical outcome of azoospermic patients rather than the sperm retrieval methods.

Analysis of cyclin-dependent kinase inhibitor 1B mutation in Han Chinese women with premature ovarian failure.

The gene for cyclin-dependent kinase inhibitor 1B (CDKN1B; also known as P27(KIP1) and P27) encodes a cyclin-dependent kinase inhibitor and controls ovarian development in mice. In p27-deficient (p27(-/-)) mice, the overactivated follicular pool in ovaries was largely depleted, causing premature ovarian failure. The goal of this research was to investigate whether there are nucleotide changes in the CDKN1B gene of Han Chinese women with premature ovarian failure, as compared with control volunteers using candidate gene sequencing. No novel variations were found in exons encoding for CDKN1B. So the mutations in CDKN1B are not common with premature ovarian failure in Han Chinese women.

Increased New lncRNA–mRNA Gene Pair Levels in Human Cumulus Cells Correlate With Oocyte Maturation and Embryo Development

The close relationship between cumulus cells and oocyte indicates that the analysis of cumulus gene expression is a potential noninvasive method to aid embryo selection and in vitro fertilization outcome. Long noncoding RNAs (LncRNAs) could regulate essential pathways that contribute to human oocyte maturation, fertilization, and embryo development, which indicates that lncRNA would be valuable biomarkers. In our previous study, AK124742 is a newly detected lncRNA that was identified as being natural antisense to PSMD6, but its role in oocyte and embryo development is still not elucidated and needs to be investigated. Here, the expression of AK124742 and PSMD6 was measured in 40 pairs of cumulus cells from oocytes that result in high-quality embryos (HCCs) and from oocytes that result in poor-quality embryos (PCCs) by real-time quantitative reverse transcriptase polymerase chain reaction. The predictive value of AK124742 and PSMD6 was evaluated using a receiver–operating characteristic (ROC) curve. Notably, elevated expression levels of AK124742 and PSMD6 were observed in HCCs compared to PCCs (72.5% and 62.5%, respectively; P < .01). Expression of AK124742 was potentially positively associated with the PSMD6 levels. The relative expression levels of AK124742 and PSMD6 in the pregnancy group were significantly higher than those in the nonpregnancy group (P < .01).The area under the ROC curve of AK124742 was 0.78 (95% confidence interval: 0.64-0.93). In conclusion, AK124742 and PSMD6 as a new lncRNA–messenger RNA gene pair in human cumulus cells may be considered as potential biomarkers to aid embryo selection.

YAP induces cisplatin resistance through activation of autophagy in human ovarian carcinoma cells

Objective To identify the role of YAP in cisplatin resistance in human ovarian cancer cells and in the regulation of autophagy in these cancer cells. Materials and methods The cisplatin-sensitive OV2008 parental cell line and its cisplatin-resistant variant C13K were cultured. RNA interference was used to knock down the YAP gene. Accumulation of GFP-LC3 puncta was performed by fluorescence microscopy. The formation of autophagosomes was observed by transmission electron microscopy. Drug sensitivity was examined using CCK-8 assay, while apoptosis, the level of intracellular rhodamine 123 and lysosomal acidification were analyzed by fluorescence-activated cell sorting. Acid phosphatase activity was measured using an acid phosphatase-assay kit. Real-time polymerase chain reaction, Western blotting, and immunofluorescence detection were used to detect the protein and messenger RNA expression of YAP, YAP target genes, CCND1, cleaved PARP, and caspase 3, Atg-3 and -5, and the LC3B protein. Results YAP signaling may regulate cisplatin resistance in ovarian cancer cells by augmenting cellular autophagic flux. After knockdown of YAP-sensitized C13K cells to cisplatin by inducing a decrease in autophagy, YAP led to an increase in autophagy via enhancement of autolysosome degradation. Conclusion YAP-mediated autophagy may play a protective role in cisplatin-resistant human ovarian cancer cells. Therefore, YAP-mediated autophagy should be explored as a new target for enhancing the efficacy of cisplatin against ovarian cancer and other types of malignancies.

Molecular Signature in Human Cumulus Cells Related to Embryonic Developmental Potential

Identification of criteria for embryo quality is required to improve the clinical outcome of in vitro fertilization. The aim of this study was to determine the gene expression profile of cumulus cells (CC) surrounding the oocyte as biomarkers for embryonic developmental potential. CCs from single oocytes were analysed using DNA microarrays. Gene expression profiles of CC surrounding the oocyte associated with good embryonic quality were analyzed. We observed that CCs issued from oocytes that developed into embryos with a good morphology had significantly different gene expression profile from those with bad morphology. These results were confirmed by quantitative RT–PCR. The gene expression profiling of human CC correlates with embryo potential. Our findings suggest anon-invasive approach, offering a new potential strategy for competent embryo selection.

The abnormal expression of oxytocin receptors in the uterine junctional zone in women with endometriosis

BackgroundThe junctional zone (JZ), also called as the endometrial-myometrial junction, is related to peristaltic-like movements in the non-pregnant uterus. Hyperperistalsis and dysperistalsis of uterus constructions might underlie many important disorders such as dysmenorrhea, infertility, endometriosis, implantation failure. The major proteins for uterine contraction of the non-pregnant uterus may be Oxytocin (OT) and oxytocin receptor (OTR). The objective of this study was to inspect the expression of OTR in isthmic and mid-fundal parts of the uterine junctional zone at different stages of the follicular cycle in patients with and without endometriosis.MethodsUterine biopsies containing endometrium and junctional zone were collected from the isthmic and mid-fundal parts of the anterior wall after hysterectomy. The OTR expression was evaluated by immunohistochemistry.ResultsIn the control uterus, OTR expression in the isthmic region was significantly higher than in the fundal region in the proliferative phase (p < 0.05) but significantly lower in the secretory phase (p < 0.05). And the expression of OTR in the proliferative phase was significantly higher than that in the secretory phase in both isthmic and fundal regions (p = 0.000 and 0.049, respectively). However, in endometriosis uteri, OTR expression in the isthmic region showed no significant difference with that in the fundal region in both proliferative and secretory phases (p = 0.597 and 0.736, respectively). In both isthmic and fundal regions, OTR expression was not significantly different between the proliferative phase and secretory phase (p = 0.084 and 0.222, respectively). OTR expression in fundal regions of revised ASRM I and II endometriosis were lower than that of revised ASRM III and IV (p = 0.049). In the fundal region of JZ, the expression of OTR in ovarian endometriosis was significantly lower than that in deep infiltrating endometriosis (p = 0.046). The expression level of OTR in the funds region is positively associated with the severity of dysmenorrhea in endometriosis group (r = 0.870, p < 0.05). Comparing to normal uteri, the expression of OTR in the secretory phase was significantly higher in the endometriosis uteri (p < 0.05). In the fundus of endometriosis uteri, OTR expression was significantly higher in both the proliferative and secretory phases (p = 0.045 and 0.028, respectively).ConclusionOTR expression in the JZ of women with endometriosis changes significantly, which may result in abnormal uterine contractile activity, reducing the endometriosis-related fertility and dysmenorrhea.