The use of oxytocin in experimental models of the human female genital tract with implications for HIV susceptibility

Simple item page
dc.contributor.authorPlesniarski, Andrew
dc.contributor.examiningcommitteeWylie, John (Medical Microbiology and Infectious Diseases)
dc.contributor.examiningcommitteeTriggs-Raine, Barbara (Biochemistry and Medical Genetics)
dc.contributor.examiningcommitteeLin, Rongtuan (McGill University)
dc.contributor.supervisorSu, Ruey-Chyi
dc.contributor.supervisorBall, Terry
dc.date.accessioned2024-11-20T20:21:16Z
dc.date.available2024-11-20T20:21:16Z
dc.date.issued2024-11-18
dc.date.submitted2024-11-18T20:34:46Zen_US
dc.degree.disciplineMedical Microbiology and Infectious Diseases
dc.degree.levelDoctor of Philosophy (Ph.D.)
dc.description.abstractIntroduction: Oxytocin has been implicated in reductions in inflammation at skin and gut epithelia, as well as improved wound healing outcomes in small animal models and clinical trials of skin wounds. Susceptibility to HIV infection at the female genital tract (FGT) has been associated with increased levels of inflammation and breakdown of the epithelial barrier. I sought to investigate whether oxytocin could 1) reduce inflammation and improve wound healing of FGT epithelial cells and 2) reduce susceptibility to vaginal HIV infection in a humanized mouse model. Methods: VK2/E6E7 (Vk2), Ect1/E6E7 (Ect1), and End1/E6E7 (End1) cell lines were used to model vaginal, ectocervical, and endocervical cells, respectively. Inflammation was assessed by the levels of pro-inflammatory cytokine/chemokine transcripts and secreted protein. The effect of oxytocin on wound healing was assessed using scratch assay models. Immunologically humanized mice treated longitudinally with oxytocin vaginal gel were challenged with HIV-1 and followed for ≥ 63 days. Cervicovaginal lavage, blood samples, and lymphatic tissues were collected for analysis. Additional analysis of oxytocin receptor (OXTR) expression of the FGT cell lines was performed using qPCR, Western blot, confocal microscopy, mass spectrometry, and calcium flux. Results: Media formulations for FGT epithelia were found to contain oxytocin. After correction of this factor using alternative culture media, it was found that oxytocin modulated pro-inflammatory cytokine transcript and protein levels in Ect1 and End1 cells and inhibited wound healing in Vk2 and End1 cells. OXTR validation in Vk2, Ect1, and End1 cells revealed non-significant mRNA protein levels, with oxytocin also failing to elicit calcium flux. Intravaginal administration of oxytocin gel had no effect on leukocyte activation or regulation of pro-inflammatory cytokine/chemokine expression in our humanized mice. Control mice did not succumb to HIV-1 infection, preventing conclusions on susceptibility. Conclusions: Oxytocin was found to alter pro-inflammatory cytokine expression and reduce wound healing in FGT epithelial cells in vitro, despite the absence of detectable OXTR expression. Additionally, FGT media formulations were found to confound previous oxytocin studies due to inherent oxytocin levels. Vaginal oxytocin gel did not affect leukocyte activation or cytokine levels in humanized mice, with further work on HIV-1 susceptibility needed.
dc.description.noteFebruary 2025
dc.identifier.urihttp://hdl.handle.net/1993/38674
dc.language.isoeng
dc.subjectHIV
dc.subjectOxytocin
dc.subjectFemale Genital Tract
dc.titleThe use of oxytocin in experimental models of the human female genital tract with implications for HIV susceptibility
local.subject.manitobano
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Andrew Plesniarski PhD Thesis for MSpace Nov. 18. 2024 Final.pdf
Size:
8.46 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
770 B
Format:
Item-specific license agreed to upon submission
Description:
Download
Collections
FGS - Electronic Theses and Practica