Joint MiRNA/mRNA expression profiling reveals rhanges consistent with development of dysfunctional corpus luteum after weight gain

<div><p>Obese women exhibit decreased fertility, high miscarriage rates and dysfunctional corpus luteum (CL), but molecular mechanisms are poorly defined. We hypothesized that weight gain induces alterations in CL gene expression. RNA sequencing was used to identify changes in the CL transcriptome in the vervet monkey (<i>Chlorocebus aethiops</i>) during weight gain. 10 months of high-fat, high-fructose diet (HFHF) resulted in a 20% weight gain for HFHF animals vs. 2% for controls (p = 0.03) and a 66% increase in percent fat mass for HFHF group. Ovulation was confirmed at baseline and after intervention in all animals. CL were collected on luteal day 7–9 based on follicular phase estradiol peak. 432 mRNAs and 9 miRNAs were differentially expressed in response to HFHF diet. Specifically, miR-28, miR-26, and let-7b previously shown to inhibit sex steroid production in human granulosa cells, were up-regulated. Using integrated miRNA and gene expression analysis, we demonstrated changes in 52 coordinately regulated mRNA targets corresponding to opposite changes in miRNA. Specifically, 2 targets of miR-28 and 10 targets of miR-26 were down-regulated, including genes linked to follicular development, steroidogenesis, granulosa cell proliferation and survival. To the best of our knowledge, this is the first report of dietary-induced responses of the ovulating ovary to developing adiposity. The observed HFHF diet-induced changes were consistent with development of a dysfunctional CL and provide new mechanistic insights for decreased sex steroid production characteristic of obese women. MiRNAs may represent novel biomarkers of obesity-related subfertility and potential new avenues for therapeutic intervention.</p></div

Using Basic Science to Design a Clinical Trial: Baseline Characteristics of Women Enrolled in the Kronos Early Estrogen Prevention Study (KEEPS)

Observational and epidemiological studies suggest that menopausal hormone therapy (MHT) reduces cardiovascular disease (CVD) risk. However, results from prospective trials showed neutral or adverse effects most likely due to differences in participant demographics, such as age, timing of initiation of treatment, and preexisting cardiovascular disease, which reflected in part the lack of basic science information on mechanisms of action of hormones on the vasculature at the time clinical trials were designed. The Kronos Early Estrogen Replacement Study (KEEPS) is a prospective, randomized, controlled trial designed, using findings from basic science studies, to test the hypothesis that MHT when initiated early in menopause reduces progression of atherosclerosis. KEEPS participants are younger, healthier, and within 3 years of menopause thus matching more closely demographics of women in prior observational and epidemiological studies than women in the Women’s Health Initiative hormone trials. KEEPS will provide information relevant to the critical timing hypothesis for MHT use in reducing risk for CVD

Analyse beckenweiter interner Wellen im Bodensee-Obersee

Available from TIB Hannover: RA 1064(123) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Coronary Artery Vitamin D Receptor Expression and Plasma Concentrations of 25-Hydroxyvitamin D: Their Association with Atherosclerosis.

OBJECTIVE: The aim of this study was to analyze coronary artery vitamin D receptor (VDR) expression, the plasma concentrations of 25-hydroxyvitamin D3 (25OHD3), and their relationship with coronary artery atherosclerosis. METHODS: Premenopausal cynomolgus monkeys were fed atherogenic diets containing the equivalent of 1,000 IU/day of vitamin D3. Protein was derived from casein-lactalbumin (C/L, n = 10), soy protein isolate (soy, n = 10), or a combination (n = 19). After 32 months of consuming the diets, each monkey underwent surgical menopause. After 32 postmenopausal months, coronary atherosclerosis was measured in the left circumflex (LCX) artery and left anterior descending (LAD) artery. VDR expression was determined for the LAD, and 25OHD3 concentrations were assessed. RESULTS: Both the cross-sectional area of atherosclerotic plaques (in square millimeters) and plaque thickness (in millimeters) in the LCX as well as the LAD arteries were analyzed in these monkeys. Those with higher plasma vitamin D3 concentrations and higher VDR were compared with those with higher plasma 25OHD3 concentrations and lower VDR. Significantly smaller plaque sizes were noted with higher plasma 25OHD3 concentrations and higher VDR. For the LCX artery, there was also a significantly lower plaque size (both plaque thickness and cross-sectional area) in those with higher quantities of VDR and lower 25OHD3 concentrations versus those with lower quantities of VDR and higher plasma concentrations of 25OHD3 (P = 0.009 and P = 0.040, respectively). CONCLUSIONS: Cynomolgus monkeys with higher quantities of VDR have significantly less atherosclerosis than do those with lower quantities of VDR and higher plasma 25OHD3 concentrations. If these findings translate to human beings, it might explain why some individuals with higher plasma concentrations of 25OHD3 have more coronary artery atherosclerosis