Hyperandrogen-induced polyol pathway flux increase affects ovarian function in polycystic ovary syndrome via excessive oxidative stress.

AIMS: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in the women of childbearing age. It is characterized by hyperandrogenism and abnormal follicular growth and ovulation. The polyol pathway is a glucose metabolism bypass pathway initiated by aldose reductase (ADR). Androgen induces the expression of ADR in the male reproductive tract, which has a general physiological significance for male reproductive function. Here we investigate whether hyperandrogenemia in PCOS leads to increased flux of the polyol pathway in ovarian tissue, which in turn affects follicular maturation and ovulation through oxidative stress. MAIN METHODS: We used clinical epidemiological methods to collect serum and granulosa cells from clinical subjects for a clinical case-control study. At the same time, cell biology and molecular biology techniques were used to conduct animal and cell experiments to further explore the mechanism of hyperandrogen-induced ovarian polyol pathway hyperactivity and damage to ovarian function. KEY FINDINGS: Here, we find that hyperandrogenism of PCOS can induce the expression of ovarian aldose reductase, which leads to the increase of the polyol pathway flux, and affects ovarian function through excessive oxidative stress. SIGNIFICANCE: Our research has enriched the pathological mechanism of PCOS and may provide a new clue for the clinical treatment of PCOS.

Comparisons on perinatal depression between the first-child women and the second-child women in West China under the universal 2-child policy: A STROBE compliant prospective cohort study.

BACKGROUND: Universal 2-child policy was proposed in 2015 in China, but it was still uncertain whether having a second child would have any impacts on maternal health, especially mental health. So, the aim of this study was to compare the incidence of perinatal depression between the first-child women and the second-child women and to describe the patterns of perinatal depression from the first and third trimesters to 6 weeks postpartum. METHODS: A prospective cohort study was conducted in a university hospital, 969 first-child women and 492 second-child women registered in this hospital from Dec 2017 to Mar 2018 were involved in the study. The Mainland Chinese version of the Edinburgh Postnatal Depression Scale (EPDS) was applied to screen perinatal depressive symptoms, while socio-demographic and obstetric data were obtained by self-administered questionnaires. Multiple logistic regression analyses were used to compare the risk of depression between 2 groups, and repeated measures of analysis of variances (ANOVAs) were used to determine the EPDS scores of 2 groups across 3 stages. RESULTS: The incidence of perinatal depression was 21.78% to 24.87% and 18.29% to 22.15% in the first-child group and the second-child group, respectively. The second-child women were less likely to exhibit depressive symptoms than the first-child women in the first trimester (Adjusted OR = 0.630, 95%CI = 0.457-0.868, P = .005), but no significant difference was found between the 2 groups in the third trimester and at postpartum period. During the whole perinatal period, no significant difference was found in EPDS scores of the first-child group among the three stages. However, the EPDS scores of the second-child group were higher in the first trimester than that at the postpartum period. CONCLUSION: The risk of perinatal depression for the second-child women was no higher than for the first-child women, and the EPDS scores of the second-child women were decreasing during the perinatal period. So couples in West China are recommended to consider having a second child without much worry about its negative effects on mental health under the universal 2-child policy.

Bisphenol A Initiates Excessive Premature Activation of Primordial Follicles in Mouse Ovaries via the PTEN Signaling Pathway.

The essence of primary ovarian insufficiency (POI) is the premature exhaustion of primordial follicles in the follicle pool, which is caused by the excessive premature activation of primordial follicles after birth. Bisphenol A (BPA) exposure promotes the transition of primordial follicles to primary follicles, thus the number of primordial follicles in the primordial follicle pool decreases significantly. However, the molecular mechanisms underlying abnormal follicle activation are poorly understood. Phosphatase and tensin homologue (PTEN) signal system is a negative regulator of follicle activation, which is called the brake of follicle activation. Besides, BPA induces Michigan Cancer Foundation-7 breast cancer cells proliferation by dysregulating PTEN/serine/threonine kinase/p53 axis. Whether BPA initiates the excessive premature activation of primordial follicles in the mouse ovaries via PTEN signaling pathway is unclear. In this study, we treated 6-week-old female CD-1 mice with different concentrations of BPA to study the effect of BPA on follicular activation and development in vivo, as well as the role of PTEN signaling in this process. We observed that BPA in concentrations from 1 µg/kg to 10 mg/kg groups downregulated PTEN expression and initiated excessive premature activation of primordial follicles in the mouse ovaries, and this effect was partly reversible by PTEN overexpression. Our results improve the understanding of both the effect of BPA in occurrence of POI and molecular mechanisms underlying initiation of primordial follicle pool activation, thus providing insight for POI treatment and theoretical basis for reducing the risk of POI.

[Correlation Between Dietary Nutrition and Premature Ovarian Failure].

OBJECTIVE: To explore the relationship between dietary nutrition and premature ovarian failure (POF). METHODS: A case control study was undertaken in 294 patients recruited from the reproductive endocrine clinic of our hospital over the period from November 2015 to January 2017. The POF group included women with premature ovarian failure , and women with normal menstruation were included as control group. The dietary and nutritional status of these patients were analyzed and compared. RESULTS: A total of 70 POF patients (POF group) and 224 controls participated in this study. No significant differences in age, sex, height, body mass and body mass index (BMI) existed between the two groups. Significant differences were found between the two groups in daily intakes of protein, carbohydrate and dietary fiber (P<0.05). Low carbohydrate (OR=11.652, 95% CI: 3.864-35.135) and dietary fiber intake (OR=7.851, 95% CI: 2.272-27.137) were associated with higher odds of POF. CONCLUSION: Deficiencies of carbohydrate and dietary fiber are associated with premature ovarian failure.

Age will affect the Growth and Mineralization Ability of the Rat Osteoblast.

BACKGROUND: Primary culture of rat osteoblast cells serves as a model in in vitro research of bone metabolism. But most of studies about osteoblast use fetal or newborn rats for cell isolation, including researches about the post-menopausal osteoporosis. This will affect the authenticity and reliability of the results. These differences have been a concern in recent years. So far, little research has focused on adult female rat osteoblasts. METHODS: In this study, a systematic study was done regarding the proliferation, differentiation, and mineralization of adult female rat osteoblasts. RESULTS: The study showed that the age of the host may affect the growth and the mineralization ability of osteoblast. CONCLUSIONS: The result of the study suggests that in vitro studies related to osteoblasts should select the right host and appropriate observation points according to the cell growth characteristics in order to ensure the consistency of the actual changes.

Meta-analysis of association between GSTM1 gene polymorphism and cervical cancer.

OBJECTIVE: To investigate association between glutathione S-transferases (GSTs) and cervical cancer. METHODS: Published literature from PubMed, EMBASE, and other databases were retrieved. All studies evaluating the association between GSTM1/GSTT1 polymorphisms and cervical were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed- or random-effects model. RESULTS: A total of 15 case-control studies were included in the meta-analysis of GSTM1 genotypes (1,825 cases and 2,104 controls). The overall result showed that the association between GSTM1 null genotype and risk for cervical cancer was statistically significant (OR=1.53, 95%CI=1.18-2.00). Great heterogeneity was found between studies. Subgroup analysises were performed based on smoking and ethnicity. Our results showed that smokers with null GSTM1 genotype had higher risk of cervical cancer (OR=1.56, 95%CI=1.01-2.41). For the ethnicity stratification, significant increased risk of null GSTM1 genotype was found in Chinese and Indian population, but no increased risk in other population. CONCLUSIONS: This meta-analysis provides strong evidence that the GSTM1 null genotype is associated with the development of cervical cancer, and especially in Chinese and Indian population, and smoking shows a modification on the association between GSTM1 null genotype and cervical cancer.

[Effects of eight environmental endocrine disruptors on insulin resistance in patients with polycystic ovary syndrome: a preliminary investigation].

OBJECTIVE: To investigate the relationship between 8 endocrine-disrupting chemicals in the serum and insulin resistance in patients with polycystic ovary syndrome (PCOS). METHODS: This study was conducted among 60 patients with PCOS, including 23 with insulin resistance (PCOS-IR) and 37 without insulin resistance (PCOS-NIR), and 29 non-PCOS women seeking medical attention for infertility or menstrual disorder (control group). The serum levels of 6 phthalic acid esters (PEAs), bisphenol A (BPA) and octylphenol (OP) were measured in all the subjects. RESULTS: The levels of PAEs, BPA and OP showed no significant differences between PCOS patients and the control group (P>0.05). The serum level of OP was significantly lower in patients PCOS-IR than in those with PCOS-NIR (47.89 ng/ml vs 60.24 ng/ml, P<0.05). CONCLUSION: PEAs and BPA do not produce obvious effect on the pathogenesis of PCOS or contribute to insulin resistance, but OP may play a role in insulin resistance in PCOS patients.

Effects of different cryoprotectants and cryopreservation protocols on the development of 2-4 cell mouse embryos.

This study evaluated the effects of different cryoprotectants and cryopreservation protocols on the development of in vivo fertilized 2-4 cell mouse embryos. Mouse embryos were cryopreserved by using propylene glycerol (PG), ethylene glycerol (EG), dimethyl sulfoxide (DMSO) or glycerol (G) as cryoprotectant with slow-freezing or Vit-Master vitrification protocol. After thawing, the survival rate, blastocyst formation rate and blastocyst hatching rate of the embryos were compared. When mouse embryos were cryopreserved by the slow-freezing, survival rate, blastocyst formation rate and blastocyst hatching rate of the embryos with PG were significantly higher than those of DMSO and G (P < 0.05, respectively), but there is no significantly difference among those of DMSO, G and EG(p > 0.05), and between PG and EG. When mouse embryos were cryopreserved by Vit-Master vitrification, survival rate, blastocyst formation rate and blastocyst hatching rate of the embryos with EG were significantly higher than those of PG, DMSO and G (P < 0.05). There were no significant differences among those of PG, DMSO and G (p > 0.05). In conclusion, PG was the optimal cryoprotectant for the cryopreservation of 2-4 cell mouse embryos by slow-freezing protocol. EG was the optimal cryoprotectant for the cryopresevation of 2-4 cell mouse embryos by Vit-Master vitrification protocol, which may be commonly used in clinical and laboratory practice.

Relationship between soy food intake and breast cancer in China.

AIMS: Soy food intake may be associated with reduced risk of breast cancer, by far the most frequent cancer among women, but the results are inconsistent. We aimed to investigate the relationship further in Chinese population and to assess the importance of hormone receptor status. METHODS: A case-control study was conducted with totals of 183 cases and 192 controls recruited from January 2008 to January 2011 among patients admitted to the General Hospital of PLA and the Second Affiliated Hospital of Guangzhou Medical University, China. Trained interviewers conducted face-to-face interviews using a structured questionnaire to collect information on dietary habits and potential confounding factors. RESULTS: The highest relative to lowest soy isoflavone intake was associated with a 58% decrease risk of breast cancer (OR=0.42, 95% CI=0.22-0.80). Higher consumption of soy protein also decreased breast cancer risk, and the highest consumption reduced 54% cancer risk compared with the lowest (OR=0.46, 95%CI=0.24-0.88). The inverse association between highest intake of soy isoflavone and soy protein with the risk of breast cancer was statistically in postmenopausal women (OR=0.57, 95%CI=0.29-0.83; OR=0.50, 95%CI=0.38-0.95). In the ER/PR status stratified analysis, a significantly reduced risk was observed for ER+/PR+ breast cancer among highest intake of soy isoflavone and soy protein, with ORs of 0.47 and 0.63, respectively. CONCLUSION: Our study suggested that a high intake of soy food is inversely associated with breast cancer risk, the effect depending to some extent on the hormone receptor status.

[Effects of Kuntai Capsule and hormone replacement therapy on cognitive function and mental symptoms of early postmenopausal women: a randomized controlled trial].

BACKGROUND: Conjugated equine estrogen (CEE) treatment, a hormone replacement therapy, is restricted for use in perimenopausal and postmenopausal women because of security issues. Consequently, traditional Chinese herbal medicine has become an alternative choice for the patients with contraindications to hormone replacement therapy. OBJECTIVE: To evaluate the efficacy and safety of Kuntai Capsule and CEE in treating cognitive function disorder and mental symptoms of early postmenopausal women. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 57 cases of early postmenopausal women from Outpatient Department of West China Women and Children's Hospital were included. The subjects were randomly divided into two groups: Kuntai group with 28 cases and CEE group with 29 cases. The patients in Kuntai group received 6 g Kuntai capsules three times a day. The patients in CEE group received CEE 0.3 mg and 0.6 mg alternately once a day (average dose of 0.45 mg/d). The patients with intact uterus in CEE group were treated with 2 mg medroxyprogesterone acetate daily. MAIN OUTCOME MEASURES: In one-year treatment course, the recognition function and mental symptoms of each patient were investigated by questionnaires of Mini-Mental State Examination (MMSE), Kupperman, and quality of life (QOL) every three months. Both intention-to-treat (ITT) and per-protocol set (PPS) analyses were done. RESULTS: The MMSE, Kupperman index and QOL scores at each time point were improved as compared with those before treatment (P<0.05), however there were no statistical differences between the two groups (P>0.05). The MMSE scores showed a tendency to escalate while mental symptoms investigated by Kupperman index and QOL scale showed a downtrend. No severe adverse effects occurred in the study phase and no statistical difference in incidence of side effects between the two groups was found except for vaginal bleeding. The incidence rates of vaginal bleeding in CEE and Kuntai groups were 39.3% and 11.1% respectively (P=0.029). CONCLUSION: Both Kuntai Capsule and CEE may contribute to maintain the cognitive function and ameliorate mental symptoms of early postmenopausal women.

[Autophosphorylation of erythrocyte insulin receptors in patients with polycystic ovary syndrome].

OBJECTIVE: To investigate the tyrosine autophosphorylation of insulin receptors in patients with polycystic ovary syndrome (PCOS). METHODS: Forty patients with PCOS and 20 age- and body mass index matched healthy women were included in the study. The patients with PCOS were classified as HI-PCOS (n=20) or non-HI-PCOS (n=20) based on the fasting insulin level (>or< or =15 mIU/L). 1) Serum gonadotropins and ovarian steroids were determined. Oral glucose tolerance tests (OGTT) and insulin releasing tests were performed to calculate the insulin resistance index (HOMA-IR). 2) Blood samples were obtained at five time-points during the OGTT (Fasting and 30 min, 60 min, 120 min, and 180 min after taking 75 g glucose orally). The erythrocytes were isolated and the autophosphorylation insulin receptors (APIR) and total insulin receptors (TIR) were measured by enzymatic immunoassay. 3) The in vivo autophosphorylation of insulin receptors was indicated by the APIR/TIR ratio. RESULTS: The HI-PCOS patients had lower APIR/TIR ratio than the non-HI-PCOS patients and healthy controls at the 60th minute after OGTT (P<0.05). No differences in other time-points were significant. CONCLUSION: The autophosphorylation of insulin receptors in HI-PCOS patients decrease, which might be a mechanism for insulin resistance in patients with PCOS.

[Sexual hormone and traditional Chinese patent medicine for early postmenopausal women: effect on quality of life and cost-utility analysis].

OBJECTIVE: To evaluate the effect of Premarin and Kuntai capsule (a traditional Chinese patent medicine) on the quality of life (QOL) and their cost-utility in early postmenopausal women. METHODS: Fifty-seven women with menopausal syndrome in the early postmenopausal stage were randomly allocated into Premarin group (0.3 mg/day and 0.6 mg/day alternately, n=29) and Kuntai group (4 g/day, n=28). The therapies lasted for one year and the patients were followed up every 3 months. The QOL of the patients was evaluated and the utility scores were obtained from rating scale to conduct a cost-utility analysis (CUA). RESULTS: At each follow-up examination, no significant difference was found in the QOL between the two groups (P>0.05). The QOL obviously increased after the 1-year-long therapy in both the groups, and Kuntai required longer treatment time than Premarin to take effect. The cost-utility ratio of Premarin and Kuntai were 13581.45 yuan/QALY (quality adjusted life year) and 25105.12 yuan/QALY, respectively. Both incremental cost analysis and sensitivity analysis showed that Kuntai was more costly than Premarin. The result of per-protocol analysis was consistent with that of intention-to-treat analysis. CONCLUSION: At early stage of menopause, the QOL of women with menopausal syndrome can be significantly improved by low-dose Premarin and Kuntai capsule, but the latter is more costly.

[Effect of weight on bone mineral density in ovariectomic rats].

OBJECTIVE: To evaluate the effect of weight on bone mineral density in ovariectomic rats. METHODS: Forty 6-month-old Wistar female rats were randomly divided into the sham surgical group and the ovariectomic group. The weights of the rats and the bone mineral densities and bone mineral contents of the femurs of the rats were measured eight weeks after the operations. RESULTS: The body weights of the ovariectomic rats increased significantly. The vaginal cytology of the ovariectomic rats showed no estrous cycle. The areas of the uterus transverse section of the ovariectomic rats deceased significantly. The depth of endometrium and its epithelia, and the area percentage of endometric gland of the ovariectomic rats were smaller than those of the sham surgical controls. There were no statistically differences in the BMD and BMC between the ovariectomic rats and the sham surgical controls. However, the BMC/weight ratio of the ovariectomic rats decreased significantly. The linear stepwise regression analysis indicated a positive correlation between BMC and body weight and a negative correlation between BMC and the weight differences pre- and post operations. The BMC/weight ratio also had a negative correlation with the weight differences. CONCLUSION: The osteoporotic animal model after ovariectomy has been successfully established. The certain increased body weight after ovariectomy may slow the lose of bone mass. But the over increasing in body mass lead to BMC/weight decling, caused by osteoporosis.

[Reliability and validity regarding the Chinese version of the International Physical Activity Questionnaires (long self-administrated format) on women in Chengdu, China].

OBJECTIVE: To test the reliability and validity of International Physical Activity Questionnaires (long self-administrated format) (IPAQ), Chinese version on women of 12 - 44 years old, in Chengdu city. METHODS: Clustered sampling was used, according to the age distribution of investigated population. One community, one university and two middle schools (including one high school and one junior high school) in Chengdu were selected. The reliability study was conducted in a 28-day period. Participants were contacted three times within 28 days (on the 1(st), the 8(th) and the 28(th) day respectively). In the validity study, participants completed the same questionnaire and Bouchard physical activity diary (PA diary) each day for seven days between visit 1 and visit 2 before comparing the IPAQ's result with Bouchard physical activity diary's for validity study. Pearson or Spearman' correlation coefficients were calculated for validity and interclass correlation coefficients for reliability according to date distribution. RESULTS: (1) One hundred and eighty six participants were recruited for the reliability study. All of them completed the first questionnaire with 143 (76.88%) and 172 (92.50%) finished the second and third questionnaires. One hundred and fifty eight participants were recruited in the validity study. Qualified questionnaire accounted for 90.59% (143). (2) Results from the test-retest reliability of the Chinese version of long self-administrated format (IPAQ) showed: the ICC after one week ranged from 0.7373 to 0.972 (mean: 0.870) which were higher than those interval's reliability [ICC = 0.472 - 0.948 for three weeks interval (mean: 0.721), and 0.473 - 0.925 for four weeks interval (mean: 0.696)]. The ICCs of three weeks interval and four weeks interval were not significantly different. ICCs for vigorous physical activity and leisure time physical activity were the best. (3) The validity for different intensity, total physical activity and sitting time showed the correlation coefficients between IPAQ and PA diary ranged from 0.445 to 0.696, with correlation for vigorous physical activity the best (r = 0.696). CONCLUSION: IPAQ-C seemed a reliable and validated measure of physical activity for 12 - 44 year-old women in Chengdu city.

[The relationship between leptin, insulin-like growth factor-1 (IGF-1) and hyperinsulinemia of patients with polycystic ovarian syndrome].

OBJECTIVE: To identify the effect of IGF-1 and leptin on the hyperinsulinemia (HI) of patients with polycystic ovarian syndrome (PCOS). METHODS: The case-control compared method was applied to the study. Ninety-two PCOS and 92 control subjects were involved in the study. The group of PCOS was further divided into two subgroups of 46 PCOS-HI and 46 PCOS-NHI. The leptin, IGF-1 and other hormones such as serum testosterone, DHT, DHEA, DHEA-S were measured by RIA method. RESULTS: Leptin and IGF-1 were higher in PCOS group (16.8 +/- 9.8 ng/mL, 214.8 +/- 131.6 ng/mL) than those in control group (11.6 +/- 6.8 ng/ mL, 118.0 +/- 82.9 ng/mL respectively, P < 0.05). Serum leptin level was higher in hyperinsulinemia group (9.2 +/- 10.2 ng/mL) than that in normal insulin group (12.5 +/- 7.6 ng/mL, P < 0.05). IGF-1 (208.7 +/- 109.7 ng/mL vs. 151.7 +/- 120.0 ng/mL, P = 0.66) and fasting glucose (5.1 +/- 0.5 mmol/L vs. 4.9 +/- 0.4 mmol/L, P = 0.15) had no significant difference between two groups. Multiple logistic regression showed that after the body mass index (BMI) adjusted, the testosterone, LH/FSH, DHT, DHEA, and DHEA-S, leptin and IGF-1 showed to be the independent risk factor for PCOS, but not to be for hyperinsulinemia in patients with PCOS. CONCLUSION: The leptin and IGF-1 may contribute to the pathogenesis of PCOS, but the relationship between leptin, IGF-1 and hyperinsulinemia needs more researches to confirm.