Adipose-Derived Stromal Vascular Fraction Cell Effects on a Rodent Model of Thin Endometrium

<div><p>Endometrial dysfunction affects approximately 1% of infertile women, and there is currently no standard therapy for improving fertility treatment outcomes in these patients. In our study, we utilized a rodent model of thin endometrium to test whether intrauterine application of adipose-derived stromal vascular fraction cells (SVF) could improve morphological and physiological markers of endometrial receptivity. Using anhydrous ethanol, endometrial area and gland density were significantly reduced in our model of thin endometrium. Application of SVF was associated with a 29% reduction in endometrial vascular endothelial growth factor (VEGF) expression and significant increases in uterine artery systolic/diastolic velocity ratios and resistance index values, suggesting reduced diastolic microvascular tone. However, no significant improvements in endometrial area or gland density were observed following SVF treatment. 3D confocal imaging demonstrated poor engraftment of SVF cells into recipient tissue, which likely contributed to the negative results of this study. We suspect modified treatment protocols utilizing adjuvant estrogen and/or tail vein cell delivery may improve SVF retention and therapeutic response in subsequent studies. SVF is an easily-obtainable cell product with regenerative capability that may have a future role in the treatment of infertile women with endometrial dysfunction.</p></div

Association between cigarette smoking and ovarian reserve among women seeking fertility care.

IntroductionThis study examined the association of smoking with ovarian reserve in a cross-sectional study of 207 women enrolled in the Louisville Tobacco Smoke Exposure, Genetic Susceptibility, and Infertility (LOUSSI) Study and assessed effect modification by NAT2 acetylator phenotype.MethodsInformation on current smoking status was collected using a structured questionnaire and confirmed by cotinine assay. Serum anti-Müllerian hormone (AMH) levels were used to assess ovarian reserve. Diminished ovarian reserve (DOR) was defined as AMH ResultsCurrent smoking status, either passive or active as measured by urinary cotinine assay, was not significantly associated with DOR. For dose-response assessed using self-report, the odds of DOR increased significantly for every additional cigarette currently smoked (Odds ratio, OR:1.08; 95% confidence interval, 95%CI:1.01-1.15); additionally, every 1 pack-year increase in lifetime exposure was associated with an increased odds of DOR among women without PCOS (OR: 1.08 95%CI: 0.99-1.18). These trends appear to be driven by the heavy or long-term smokers. Effect modification by NAT2 genotype was not established.ConclusionA history of heavy smoking may indicate increased risk of diminished ovarian reserve

(A,B) Expression of vascular endothelial growth factor (VEGF) and β-actin measured by Western blot revealed no significant differences across experimental groups. Representative images of endometrial DAPI (C), green fluorescent protein (D), and rhodamine (E) expression measured by immunohistochemistry in an injured-control horn. A significant reduction in VEGF expression normalized to DAPI was collectively noted across experimental groups that received SVF treatment (asterisk), though no significant differences were noted between individual groups (F).

<p>Error bars represent standard deviation. Scale bar = 100 μm.</p

Mean systolic to diastolic (S/D) ratio (A) and resistance index (B) values plotted prior to injury, prior to treatment, and at explant.

<p>Increases in both metrics were noted in experimental groups that received SVF treatment, with changes in S/D ratio reaching statistical significance (p<0.05).</p

(A) Cultured stromal vascular fraction (SVF) cells viewed under bright field microscope at 10x magnification. (B) Fluorescent imaging demonstrates green fluorescent protein (GFP+) signal from SVF cells. Scale bar = 100 μm. (C) Intrauterine instillation procedures were performed with proximal and distal hemostatic clamps in place to isolate each uterine horn. (D) Protocol timeline demonstrates the approximate schedule of injury, treatment, and analysis.

<p>Exact dates were dependent on individual estrous cycles.</p

Representative examples of uterine horn cross sections in the third estrus phase following intrauterine instillation of either phosphate-buffered saline (PBS) (A and B) or ethanol (C and D).

<p>Gross differences in endometrial area and gland density are apparent. Scale bars = 500 μm (A) and 250 μm (B).</p

Graphs of mean endometrial areas (A) and median gland densities (B) between individual experimental groups (left) and collective sham and injured groups (right).

<p>Significant differences were observed between collective sham and injured groups (asterisks). Error bars represent standard deviation (A) and Q1, Q3 (B).</p

High-fat diet-induced upregulation of exosomal phosphatidylcholine contributes to insulin resistance

High-fat diet plays a role in development of insulin resistance. Here, the authors report a mechanism that underlies the development of diet induced insulin resistance through the activation of an aryl hydrocarbon receptor mediated signalling pathway in the liver by faecal exosomes derived from intestinal cells

Effects of Antiretroviral Therapy on Immune Function of HIV-infected Adults with Pulmonary Tuberculosis and CD4+ >350 Cells/mm3

Background. Human immunodeficiency virus (HIV)–tuberculosis coinfection is associated with heightened immune activation, viral replication, and T cell dysfunction. We compared changes in T cell activation and function between patients receiving concurrent treatment for HIV-tuberculosis coinfection and those receiving treatment for tuberculosis alone