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

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

Genome Dynamics of Campylobacter jejuni in Response to Bacteriophage Predation

Campylobacter jejuni is a leading cause of food-borne illness. Although a natural reservoir of the pathogen is domestic poultry, the degree of genomic diversity exhibited by the species limits the application of epidemiological methods to trace specific infection sources. Bacteriophage predation is a common burden placed upon C. jejuni populations in the avian gut, and we show that amongst C. jejuni that survive bacteriophage predation in broiler chickens are bacteriophage-resistant types that display clear evidence of genomic rearrangements. These rearrangements were identified as intra-genomic inversions between Mu-like prophage DNA sequences to invert genomic segments up to 590 kb in size, the equivalent of one-third of the genome. The resulting strains exhibit three clear phenotypes: resistance to infection by virulent bacteriophage, inefficient colonisation of the broiler chicken intestine, and the production of infectious bacteriophage CampMu. These genotypes were recovered from chickens in the presence of virulent bacteriophage but not in vitro. Reintroduction of these strains into chickens in the absence of bacteriophage results in further genomic rearrangements at the same locations, leading to reversion to bacteriophage sensitivity and colonisation proficiency. These findings indicate a previously unsuspected method by which C. jejuni can generate genomic diversity associated with selective phenotypes. Genomic instability of C. jejuni in the avian gut has been adopted as a mechanism to temporarily survive bacteriophage predation and subsequent competition for resources, and would suggest that C. jejuni exists in vivo as families of related meta-genomes generated to survive local environmental pressures

In Situ Coordinated Analysis of Carbonaceous Chondrite Organic Matter

Microanalytical studies of carbonaceous chondrites (CCs) have identified a vast array of isotopically, chemically and texturally distinct organic components. These components were synthesized and processed within a range of physical and chemical environments, including the interstellar medium, the solar nebula and within asteroids. The nature and abundance of these molecules can be used to unravel the geochemical and isotopic record of their origins as well as their subsequent evolutionary journey

Implementing Risk Management Decisions that Optimize Nutrient Value of Dairy Manure while Minimizing Related Risk

Nutrients present in manure are increasingly receiving attention for environmental, production, and financial reasons. Dairy producers continue to strive for better ways and educational opportunities to improve profits by evaluating fertilizer and value of manure to their operation and to protect the environment. These farming decisions which help producers stay economically viable also support and stimulate their local economy, which promotes a more vital rural community. Utilizing 22 dairy nutrient management surveys, 14 on-farm workshops, 10 small group on-farm assessment workshops, one video, and individual producer visits, producers were able to make informed decisions using tools and knowledge gained to control risks associated with manure nutrients during handling, storage, and application

Priorities and opportunities for palliative and end of life care in United Kingdom health policies: a national documentary analysis.

BACKGROUND: Access to high-quality palliative care is inadequate for most people living and dying with serious illness. Policies aimed at optimising delivery of palliative and end of life care are an important mechanism to improve quality of care for the dying. The extent to which palliative care is included in national health policies is unknown. We aimed to identify priorities and opportunities for palliative and end of life care in national health policies in the UK. METHODS: Documentary analysis consisting of 1) summative content analysis to describe the extent to which palliative and end of life care is referred to and/or prioritised in national health and social care policies, and 2) thematic analysis to explore health policy priorities that are opportunities to widen access to palliative and end of life care for people with serious illness. Relevant national policy documents were identified through web searches of key government and other organisations, and through expert consultation. Documents included were UK-wide or devolved (i.e. England, Scotland, Northern Ireland, Wales), health and social care government strategies published from 2010 onwards. RESULTS: Fifteen policy documents were included in the final analysis. Twelve referred to palliative or end of life care, but details about what should improve, or mechanisms to achieve this, were sparse. Policy priorities that are opportunities to widen palliative and end of life care access comprised three inter-related themes: (1) integrated care - conceptualised as reorganisation of services as a way to enable improvement; (2) personalised care - conceptualised as allowing people to shape and manage their own care; and (3) support for unpaid carers - conceptualised as enabling unpaid carers to live a more independent lifestyle and balance caring with their own needs. CONCLUSIONS: Although information on palliative and end of life care in UK health and social care policies was sparse, improving palliative care may provide an evidence-based approach to achieve the stated policy priorities of integrated care, personalised care, and support for unpaid carers. Aligning existing evidence of the benefits of palliative care with the three priorities identified may be an effective mechanism to both strengthen policy and improve care for people who are dying

Blood levels of adiponectin and IL-1Ra distinguish type 3c from type 2 diabetes: Implications for earlier pancreatic cancer detection in new-onset diabetes

BACKGROUND: Screening for pancreatic ductal adenocarcinoma (PDAC) in populations at high risk is recommended. Individuals with new-onset type 2 diabetes mellitus (NOD) are the largest high-risk group for PDAC. To facilitate screening, we sought biomarkers capable of stratifying NOD subjects into those with type 2 diabetes mellitus (T2DM) and those with the less prevalent PDAC-related diabetes (PDAC-DM), a form of type 3c DM commonly misdiagnosed as T2DM. METHODS: Using mass spectrometry- and immunoassay-based methodologies in a multi-stage analysis of independent sample sets (n=443 samples), blood levels of 264 proteins were considered using Ingenuity Pathway Analysis, literature review and targeted training and validation. FINDINGS: Of 30 candidate biomarkers evaluated in up to four independent patient sets, 12 showed statistically significant differences in levels between PDAC-DM and T2DM. The combination of adiponectin and interleukin-1 receptor antagonist (IL-1Ra) showed strong diagnostic potential, (AUC of 0.91; 95% CI: 0.84-0.99) for the distinction of T3cDM from T2DM. INTERPRETATION: Adiponectin and IL-1Ra warrant further consideration for use in screening for PDAC in individuals newly-diagnosed with T2DM. FUNDING: North West Cancer Research, UK, Cancer Research UK, Pancreatic Cancer Action, UK