Effects of prenatal exposure to xenobiotic estrogen and the development of endometriosis in adulthood

Abstract only availableEndometriosis is an estrogen-dependent disease that affects millions of women worldwide, causing pain and infertility. While it is known that retrograde menstruation places endometrial tissue in the peritoneal cavity, it is unclear why it invades and proliferates in women with endometriosis. Studies have shown that other hormone-dependent diseases have a fetal basis (e.g. breast cancer), suggesting that the presence of different hormones before birth may alter the incidence of endometriosis in adulthood. For example, women whose mothers took the synthetic estrogen diethylstilbestrol (DES) during pregnancy had an eighty percent increased incidence of endometriosis. Thus, our hypothesis is that prenatal exposure to xenobiotic estrogen will increase the severity of endometriosis in adulthood in a mouse model of surgically-induced endometriosis. To test this hypothesis, mice were time mated and dosed with vehicle control, 100 ng/kg DES or 10,000 ng/kg DES from days 11-17 of gestation. Surgical induction of endometriosis was performed in adulthood by autotransplantation of one uterine horm. The horn was removed, opened, divided into three pieces, and sutured to the arterial cascade of the intestinal mesentery. The implants became vascularized and formed endometriotic lesions. The mice were then collected at 2 or 4 weeks post-surgery, and the following endpoints were measured: 1) uterine weight; 2) implant size; and 3) implant weight. Additionally, implants were set aside for further analysis of 1) histology; 2) estrogen receptor indicator reporter gene activity; and 3) endometriosis-related gene expression. At the conclusion of this ongoing study, we expect to show whether there is an estrogen-mediated fetal component to endometriosis.Life Sciences Undergraduate Research Opportunity Progra

Peritoneal fluid haptoglobin from women with endometriosis differentially regulates macrophage cytokine production [abstract]

Abstract only availableThe objective of this study was to define mechanisms by which haptoglobin from endometriotic lesions (eHp) which binds to macrophages modulates immune surveillance and inflammation in the peritoneal cavity by characterizing macrophage products regulated by eHp. To eliminate human macrophage variation, the established THP-1 monocyte cell line (1.0 x106 cells/mL/well, 24-well plates, RPMI 1640+L-glutamine, FBS, and antibiotics) was routinely differentiated into macrophage-like cells with low dose PMA (20 ng/mL) and concurrently treated with media only (M), serum haptoglobin (sHp) or haptoglobin purified from peritoneal fluid of women without (cHp) or with (eHp) endometriosis (10 μg/mL, 24 h). The RayBio Inflammatory Antibody Array III was used per instructions and chemiluminescene signal intensity was quantified by densitometry. Differences were evaluated by ANOVA and post hoc tests.Variation in 8 control spots per and between membranes was sHp, cHp, M. P=0.002), TNF-α (eHp>sHp, cHp, M. P=0.045), TNF-β (eHp>sHp, cHp, M. P=0.043), PDGF-BB (eHp>sHp, cHp, M. P=0.016), IL-6sR (eHp>cHp, M. PsHp>cHp, M. P=0.072), IP-10 (eHp, sHp> cHp, M. P=0.017), RANTES (eHp, sHp>cHp, M. P=0.004) and TGF-β (eHp, sHp>M, cHp. P=0.008). Unexpectedly, cHp differentially decreased IL-2 (cHp<eHp, sHp, M. P=0.001) and MCP-1 (cHp<eHp, sHp, M. P=0.023). Twenty substances were similar in all treatments; the _expression range was divided into quartiles: High: IL-8. Moderate: IL-1β, MIP-1β. Slight: IL-10, TNFsRII, TIMP-2. Minimal: ICAM, INF-gamma, I-309; IL-1α, IL-3, IL-6, IL-11, IL-12p40, IL-12p70, IL-15, M-CSF, MIP-1α, MIP-1δ and TNFsRI. Nine were not detected in any treatment: Eotaxin-1, GCSF, GM-CSF, IL-4, IL-7, IL-13, IL-17, MCP-2, MIG. Differential eHp up-regulation and cHp down-regulation of macrophage inflammatory substances indicates that the function of eHp, hence the function of macrophages in women with endometriosis is skewed compared to controls. We postulate that peritoneal macrophages interaction with eHp contributes to endometrioisis persistence and/or pathophysiologies.National Institutes of Healt

Atomic kinetic energy, momentum distribution and structure of solid neon at zero-temperature

We report on the calculation of the ground-state atomic kinetic energy, $E_{k}$, and momentum distribution of solid Ne by means of the diffusion Monte Carlo method and Aziz HFD-B pair potential. This approach is shown to perform notably for this crystal since we obtain very good agreement with respect to experimental thermodynamic data. Additionally, we study the structural properties of solid Ne at densities near the equilibrium by estimating the radial pair-distribution function, Lindemann's ratio and atomic density profile around the positions of the perfect crystalline lattice. Our value for $E_{k}$ at the equilibrium density is $41.51(6)$ K, which agrees perfectly with the recent prediction made by Timms {\it et al.}, $41(2)$ K, based on their deep-inelastic neutron scattering experiments carried out over the temperature range $4 - 20$ K, and also with previous path integral Monte Carlo results obtained with the Lennard-Jones and Aziz HFD-C2 atomic pairwise interactions. The one-body density function of solid Ne is calculated accurately and found to fit perfectly, within statistical uncertainty, to a Gaussian curve. Furthermore, we analyze the degree of anharmonicity of solid Ne by calculating some of its microscopic ground-state properties within traditional harmonic approaches. We provide insightful comparison to solid $^4$He in terms of the Debye model, in order to size the relevance of anharmonic effects in Ne.Comment: 20 pages, 7 figures. To be published in Physical Review

Atomic Scale Depth Profile of Space Weathering in an Itokawa Olivine Grain

No abstract available

Cellular and molecular basis for endometriosis-associated infertility

Endometriosis is a gynecological disease characterized by the presence of endometrial glandular epithelial and stromal cells growing in the extra-uterine environment. The disease afflicts 10%–15% of menstruating women causing debilitating pain and infertility. Endometriosis appears to affect every part of a woman’s reproductive system including ovarian function, oocyte quality, embryo development and implantation, uterine function and the endocrine system choreographing the reproductive process and results in infertility or spontaneous pregnancy loss. Current treatments are laden with menopausal-like side effects and many cause cessation or chemical alteration of the reproductive cycle, neither of which is conducive to achieving a pregnancy. However, despite the prevalence, physical and psychological tolls and health care costs, a cure for endometriosis has not yet been found. We hypothesize that endometriosis causes infertility via multifaceted mechanisms that are intricately interwoven thereby contributing to our lack of understanding of this disease process. Identifying and understanding the cellular and molecular mechanisms responsible for endometriosis-associated infertility might help unravel the confounding multiplicities of infertility and provide insights into novel therapeutic approaches and potentially curative treatments for endometriosis

Neonatal exposure to xenobiotic estrogen alters the adult immune response and exacerbates endometriosis in mice [abstract]

Faculty Mentor: Dr. Susan C. Nagel, Obstetrics/Gynecology, and Women's HealthAbstract only availableEndometriosis is a common medical condition affecting 5-10% of women worldwide, and results in severe cramps, pelvic pain, and infertility. The cause of the disease is still unknown. Endometriosis occurs when endometrial tissue, which escapes into the peritoneal cavity via retrograde menstruation, adheres to other tissues in the cavity and causes irritated, inflamed lesions. Studies have suggested that the risk of developing endometriosis increases in women who have been exposed to xenobiotic (foreign to the body) estrogens during developmental stages of life. Thus, it is our hypothesis that programming of the immune system by xenoestrogens during development could potentially exacerbate endometriosis. This could occur by altering the peritoneal environment and/or the invading endometrial tissue. Therefore, it is our goal to study the effects of neonatal xenoestrogen exposure on the immune system; and ultimately, on the establishment of endometriosis in adulthood. In order to study this response, we dosed two strains of mice (CD1 and C57) with xenobiotic estrogens on postnatal days 2-14. In experiment A, CD1 mice were dosed with vehicle control (corn oil), 20 µg/kg/day, or 200 µg/kg/day bisphenol A. In experiment B, C57 mice were dosed with a vehicle control (corn oil) or 0.1 µg/kg/day diethylstilbestrol. At 8 weeks of age, endometriosis was induced in each strain via both a surgical induction and an injection technique. At 12 weeks, the endometriotic implants were counted and weighed to determine which mice had a greater susceptibility to the condition. Our next objective will be to analyze peritoneal fluid from the treated mice to identify key immune functions (for example, the release of certain cytokines) that may have been programmed by developmental xenoestrogen exposure.Endometriosis is a common medical condition affecting 5-10% of women worldwide, and results in severe cramps, pelvic pain, and infertility.  The cause of the disease is still unknown.  Endometriosis occurs when endometrial tissue, which escapes into the peritoneal cavity via retrograde menstruation, adheres to other tissues in the cavity and causes irritated, inflamed lesions.  Studies have suggested that the risk of developing endometriosis increases in women who have been exposed to xenobiotic (foreign to the body) estrogens during developmental stages of life.  Thus, it is our hypothesis that programming of the immune system by xenoestrogens during development could potentially exacerbate endometriosis.  This could occur by altering the peritoneal environment and/or the invading endometrial tissue.  Therefore, it is our goal to study the effects of neonatal xenoestrogen exposure on the immune system; and ultimately, on the establishment of endometriosis in adulthood.  In order to study this response, we dosed two strains of mice (CD1 and C57) with xenobiotic estrogens on postnatal days 2-14.  In experiment A, CD1 mice were dosed with vehicle control (corn oil), 20 µg/kg/day, or 200 µg/kg/day bisphenol A.  In experiment B, C57 mice were dosed with a vehicle control (corn oil) or 0.1 µg/kg/day diethylstilbestrol.  At 8 weeks of age, endometriosis was induced in each strain via both a surgical induction and an injection technique.  At 12 weeks, the endometriotic implants were counted and weighed to determine which mice had a greater susceptibility to the condition.  Our next objective will be to analyze peritoneal fluid from the treated mice to identify key immune functions (for example, the release of certain cytokines) that may have been programmed by developmental xenoestrogen exposure

Lath Structured Monazite from Haughton Dome, Canada Reveals Shock-Induced Tetragonal High Pressure Polymorph of REEPO4

Shock deformed monazite, mono-clinic rare earth element (REE) phosphate, from the Haughton Dome impact structure, Nunavut, Canada, contain lath-structured lamellae. Microstructural phase heritage indicate the former presence of a previously unreported, shock-produced, tetragonal-structured, high pressure polymorph of REEPO4. This study presents an electron backscatter diffraction (EBSD) and transmission electron microscopy (TEM) study of shock deformed monazite from the historic sample DIG-9, a shock stage III, biotite sillimanite gneiss sample from near the central uplift of the Haughton Dome (7522'20"N, 8940'50"W), in which shock features in monazite were first described

Field trial evaluations of a novel persistent barrier teat dip for preventing mastitis during the dry period and as a potential substitute for dry cow antibiotic therapy

Dipping of cows at dry off and cows and heifers 10 day prepartum until calving with a persistent barrier teat dip product (developed and patented at ISU) in 2 natural exposure field trials resulted in a significantly lower IMI (particularly major environmental pathogens) at calving compared to controls. Dipping and/or dry therapy resulted in significantly lower new IMI in the early dry period compared to controls, with no difference in new IMI between treatments. Dipping of cows with a new persistent barrier teat dip provides the first cost effective, novel dry cow mastitis prevention tool focused at high susceptibility times and all causative organisms, and also can be a potential substitute for dry cow antibiotic therapy for prevention of new early dry period IMI. This also results in lowering the potential risks of antibiotic contamination of milk