Medicine and Health Sciences Commons^™

Role Of Decorin At The Fetal-Maternal Interface, Chidambra D. Halari

Electronic Thesis and Dissertation Repository

The human placenta is an invasive tumor-like structure, this invasion being physiological. A subset of placental trophoblast called extra-villous trophoblast invades the uterine decidua and remodels uterine arteries into low-resistance, high-flow tubes to permit adequate flow of maternal blood to nourish the fetus. A poor extra-villous trophoblast invasion and uterine arterial remodeling can lead to fetal growth restriction and a serious pregnancy-associated maternal disease preeclampsia. Decorin, a leucine-rich proteoglycan produced by uterine decidual cells restrains multiple trophoblast functions: self-renewal and differentiation of trophoblast stem cells, migration, invasion, proliferation and endovascular differentiation. Additionally, decidual overproduction of decorin was associated with preeclampsia, …

The Effect Of Mtor Inhibitor Rapamycin On A Dietary Drosophila Melanogaster Model Of Calcium Oxalate Nephrolithiasis, Michael T. Pignanelli

Electronic Thesis and Dissertation Repository

Impaired cellular tolerance of reactive oxygen species (ROS) has been suggested as a common mechanistic link associated with aging in both metabolic syndrome and nephrolithiasis. The mechanistic (mammalian) target of rapamycin (mTOR) activity is characteristic of metabolic syndrome. When nutrients are abundant, mTOR is active. Conversely, fasting inhibits mTOR. Metabolic syndrome is correlated with an increased risk of self-reported or imaging findings of nephrolithiasis. At the individual level, patients with a higher BMI have an increased prevalence of recurrent symptomatic nephrolithiasis, 24-hour urinary excretion of oxalate, sodium, uric acid, calcium, and phosphorous as well as lower pH. Calcium oxalate crystals …

Nutrient Sensing Pathways Mediating Igfbp1 Phosphorylation In Fgr, Shapnil Bhuiyan

Electronic Thesis and Dissertation Repository

Impairment of fetal oxygen levels and nutrient delivery contributes to fetal growth restriction (FGR), which affects 20% of pregnancies. Such cellular stress induces hepatic Insulin-like Growth Factor Binding Protein 1 (IGFBP1) phosphorylation, which sequesters Insulin-like Growth Factor 1 (IGF-I) and markedly reduces fetal growth signaling. IGFBP1 hyperphosphoryaltion in hypoxia is mediated through the mTOR signaling pathway and through the Amino Acid Response (AAR) pathway during amino acid deprivation. Hypoxia stimulates upstream mTORC1 regulators, AMPK and REDD1 which are well-established upstream regulators of one of the two mTOR complexes, mTORC1. The molecular mechanisms by which upstream mTORC1-driven processes regulate IGFBP1 phosphorylation …

Potential Role Of Extracellular Atp Released By Bacteria In Bladder Infection And Contractility, Behnam Abbasian

Electronic Thesis and Dissertation Repository

Urgency urinary incontinence (UUI), the result of conditions such as overactive bladder (OAB), could potentially be influenced by both commensal and urinary tract infection-associated bacteria. The sensing of bladder filling involves interplay between various parts of the nervous system eventually resulting in contraction of the detrusor muscle during micturition. Here we model host responses to various urogenital bacteria, firstly by using urothelial bladder cell lines and then with myofibroblast contraction assays. To measure responses, we examined calcium influx, gene expression and alpha smooth muscle actin deposition assays. We found that organisms such as Escherichia coli IA2 and Gardnerella vaginalis ATCC …

Carbohydrates And Fungal Toxin Exposure Influence The Vaginal Microbiota, Metabolome, And Reproductive Health Of Women, Stephanie L. Collins

Electronic Thesis and Dissertation Repository

The reproductive health of women is influenced by microorganisms and their metabolites, namely those representing the vaginal microbiota and those producing toxins that are ingested. To manipulate the vaginal microbiota toward a health-associated, Lactobacillusdominant state, an approach adopting prebiotic lactulose was taken. Using batch culture, lactulose supported Lactobacillus maintenance and positively altered metabolites, while not disrupting indigenous L. crispatus epithelial adherence. The vagina also harbours abundant glycogen, but initial assumptions that lactobacilli utilize it were incorrect. I have now shown that glycogen selectively stimulates organisms associated with dysbiosis and L. iners in a self-limiting manner. Other compounds such as environmental …

Non-Invasive Determination Of Pre-Clinical Markers Of Cardiovascular Diseases In Low Birth Weight And Maternal Western Diet Guinea Pig Offspring Exposed To A Postnatal Western Diet, Jacky Chiu

Electronic Thesis and Dissertation Repository

Low birth weight (LBW), and maternal Western Diet (WD) consumption have both been independently implicated to increase the risk of developing cardiovascular diseases (CVDs) in later life. These fetal programmed risks are also believed to exacerbate the effects of a postnatal WD pattern. Therefore, resulting in the development of pre-clinical markers of CVDs, such as insulin resistance (IR), coronary circulation disruptions. This thesis aimed to elucidate the roles of sub-optimal in utero growth through placental insufficiency, or chronic maternal WD consumption, and postnatal WD consumption on the long-term programming of CVDs in a guinea pig model. Early pre-clinical markers of …

Characterizing The Human Vaginal Microbiome Using High-Throughput Sequencing, Jean Megan E. Macklaim

Electronic Thesis and Dissertation Repository

The human vaginal microbiome undoubtedly has a significant role in reproductive health and for protection from infectious organisms. Recent efforts to characterize the bacterial species of the vagina using molecular techniques have uncovered an unexpected diversity. Using high-throughput sequencing I sought to describe the structure and function of the vaginal microbiome under different physiological states including healthy, bacterial vaginosis (BV), post-menopausal vaginal atrophy, and acute vulvovaginal candidiasis (VVC).

Partial 16S rRNA gene sequencing revealed that healthy, asymptomatic women most often have vaginal biotas dominated by Lactobacillus iners or L. crispatus. In contrast, BV is a heterogeneous, highly diversified condition …

Maternal And Fetal Plasma Protein Changes In Fetal Growth Restriction, Maxim D. Seferovic

Electronic Thesis and Dissertation Repository

Fetal Growth Restriction (FGR) is caused by impaired maternal-fetal exchange of oxygen and nutrients causing fetal hypoxia and starvation. A functional failure of the placenta is the underlying cause, however the pathophysiology remains unknown. The fetus adapts by limiting growth, reducing demand for metabolic substrates. Monitoring the fetal size is the primary clinical method of FGR detection, though it does not distinguish a constitutionally small fetus from a pathological. Proteomic profiling of fetal and maternal plasma was therefore undertaken for discovery of biomarkers and pathological mechanisms. As a model of hepatic secreted fetal plasma proteins, HepG2 cell secretion changes in …