Theses and Dissertations from UMD

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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM

More information is available at Theses and Dissertations at University of Maryland Libraries.

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    Roles of Female Sex Hormones in Regulating Neisseria gonorrhoeae Colonization of the Human Cervix
    (2024) Di Benigno, Sofia; Song, Wenxia; Cell Biology & Molecular Genetics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Neisseria gonorrhoeae (GC) is a human-exclusive pathogen that infects the genital tract. Gonococcal infection may present with or without symptoms and can lead to a variety of serious sequelae if left untreated, especially in female patients. Despite this, there are few models that can effectively mimic GC infection in the female reproductive tract (FRT); of these, even fewer consider the impact of the menstrual cycle, an important feature of the FRT, on GC infection. I used the human cervical tissue explant model previously developed in our lab, which can recapitulate GC infection in vivo. Tissue explants were treated with the sex hormones estradiol and progesterone to mimic various stages of the menstrual cycle and examine its impact on GC infectivity. Estradiol was used to mimic the late proliferative phase, and a combination of estradiol and progesterone was used to mimic the middle of the secretory phase. The effects of hormones on GC infectivity were examined after 72 total hours of hormone treatment and 24 hours of inoculation with GC of strain MS11. My results show that treatment with estradiol and with a combination of estradiol and progesterone both increase the level of GC colonization on the endocervix, but not on the ectocervix, compared to controls that were not treated with hormones. However, the hormone treatment did not affect GC penetration of the cervical epithelium. Both hormone treatments increased the number of GC colonies on the endocervical epithelium, and a combination of estradiol and progesterone produced an additional population of large GC colonies, leading to an increase in the average colony size. These increases in colony number and size were not associated with an increase in the expression of carcinoembryonic antigen-related cell adhesion molecules (CEACAMs), which are the host receptors for GC Opa proteins. In contrast, treatment with estradiol induced a redistribution of CEACAMs from the luminal surface to the inside of epithelial cells. Additionally, estradiol altered the morphology of endocervical epithelial cells from columnar to cuboidal, but the integrity of cell-cell junctions was unchanged. The increase in colonization under high estradiol conditions was correlated with a decrease in levels of certain pro-inflammatory cytokines and chemokines, but this decrease was not sufficient to fully explain the increase in colonization. Next, I investigated the impact of cervical mucus on GC infectivity and interactions, as gel-forming mucin MUC5B but not MUC5AC increases with estradiol at the proliferation phase. Under both hormone treatment conditions, GC were able to establish close interaction with the luminal surface of the endocervical epithelial cells, displacing membrane-spanning mucin MUC1 in the membrane. Furthermore, GC were able to diffuse through an artificial mucin hydrogel and diffused more efficiently through a MUC5AC-dominant than a MUC5B-dominant hydrogel. Gel-forming mucins collected from cervical tissue explants enhanced GC aggregation in vitro, even at very low concentrations. However, mucins collected from estradiol-treated tissues showed less impact on GC aggregation than those collected from untreated tissues or tissues treated with both estradiol and progesterone. MUC5B and MUC5AC purified from cows and pigs also increase GC aggregation in vitro with GC aggregating more in a MUC5AC- than a MUC5B-dominant mucin mixture. Taken together, my research reveals for the first time that female sex hormones regulate GC colonization at the human cervix by changing the composition of the cervical mucus, providing a mechanism of hormonal regulation underlying the varying susceptibility of female patients to mucosal GC.
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    Neuroendocrine mechanisms underlying paternal experience-induced plasticity of the hippocampus
    (2016) Hyer, Molly Melissa; Glasper, Erica R; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Evidence suggests that males, like females, undergo altered structure and function of the hippocampus postpartum, a brain region that regulates certain aspects of emotion, learning, and memory. These behaviors are beneficial for successful parenting. In maternal rodents, offspring contact contributes to postpartum hippocampal plasticity in both mothers and offspring. Fathers do not undergo pregnancy, parturition, or lactation, therefore, the impact of offspring on hippocampal plasticity is less clear. California mouse (Peromyscus californicus) fathers are highly paternal, making this monogamous species a good model of paternal care. In this species, between postnatal days 15 and 21 paternal behavior becomes more active (i.e. increased pup retrievals) to care for pups that are beginning to explore outside of the nest. I observed reduced anxiety-like behavior in fathers specifically within this temporal window. Concomitant with attenuated anxiety-like behavior, I found that fathers maintain survival of adult born neurons in the dentate gyrus of the hippocampus. Enhanced hippocampal plasticity is not restricted to adult neurogenesis, as dendritic spine density in the dentate gyrus is increased in fathers at this same time – an effect that lasts until weaning. When permanently separated from their offspring, fathers show increased passive stress coping and reduced spine density in the DG. Taken together, these data suggest that the degree of active father-offspring interaction significantly alters hippocampal plasticity in the father. Estradiol and its receptors have been implicated in alterations to anxiety and adult neurogenesis in both males and females. I observed that estrogen receptor β (Erβ) mRNA expression was elevated in whole hippocampal homogenates at PND 16 in fathers. Similarly, circulating estradiol was elevated at both PND 2 and PND 16. After inhibition of Erβ with the drug tamoxifen, the number of surviving adult born neurons was suppressed in fathers alone. Taken together, these data suggest that in fathers, hippocampal plasticity occurs concomitantly with active father-offspring contact and that this plasticity, at least structural, is driven by activation of Erβ. Understanding paternal experience-induced plasticity and the mechanisms that drive it, may help to prevent deficits in paternal behavior that can disrupt offspring development and contribute to emotional dysregulation in fathers.