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Abstract
With the decreasing fertility rate in women over the past decades, there’s a pressing demand for investigating the factors affecting female reproduction. Both endogenous factors like genetic mutations and endocrine factors, and exogenous factors like viral infection and environmental exposures, can contribute to infertility and impaired fecundity in women. In this dissertation, we used different mouse models to investigate the contributing factors in female fertility. In Chapter 2, the functions of endogenous factors lysosome and lysosomal ion channels in the corpus luteum (CL) during early pregnancy were studied. By deleting the ATPase H+ Transporting V0 Subunit D2 gene (Atp6v0d2) in Mcoln1-/- mouse model (Atp6v0d2-/-Mcoln1-/-), the impaired female fertility and deficiencies of CL histology and progesterone (P4) steroidogenesis in Mcoln1-/- were partially rescued in Atp6v0d2-/-Mcoln1-/- mice, suggesting the restored lysosomal transmembrane potential in Atp6v0d2-/-Mcoln1-/- CL and the lysosomal impacts on female fertility. In Chapter 3, the regulation of endogenous factor—P4, in uterine fluid absorption during early pregnancy were studied in the P4-deficient mouse model (RhoAf/fPgrCre/+) and control mice with the combination of exogenous P4 and P4 receptor-antagonist (RU486) treatments. By intraluminally injecting the fluorescent dye Alexa Fluor 488 Hydrazide (AH) into preimplantation uteri in the above mouse models, we found bulk absorption in uterine luminal epithelium (LE) is the major way of uterine fluid absorption on day 0.5 post-coitum (D0.5), which decreased from D0.5 to D3.5. P4-deficiency and RU486 treatment in mice decreased bulk absorption in LE in preimplantation uterine fluid absorption, while the autofluorescence dots on apical LE, most likely indicating endocytosis, had little regulation by P4 during preimplantation. In Chapter 4, we investigated the effects of exogenous factor, influenza A virus (IAV) infection, in cycling female mice. Infection with mouse-adapted H3N2 IAV (x31) decreased mouse body weights and caused lung injury, which is associated with arrested female estrous cycles and increased ovarian follicles in early developmental stages, while the histology and cellular activities in infected ovaries and uteri were comparable to uninfected counterparts. This dissertation advances our knowledge of contributing factors involved in female reproduction.