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Investigation of Factors Affecting Fertility: Chromosome Segregation Errors and Environmental Toxins

Jackson, Jodi Michelle
http://rave.ohiolink.edu/etdc/view?acc_num=case1181332723

Abstract Details

2007, Doctor of Philosophy, Case Western Reserve University, Genetics.
If a species cannot propagate, it cannot survive. Human fertility is thought to be declining, with a myriad of possible causes. The objective of this dissertation was to investigate two factors that affect fertility: chromosome segregation errors and environmental toxins. Aneuploidy affects 10-30% of human conceptions and is the leading genetic cause of pregnancy loss and mental retardation. Accordingly, the etiology of chromosome segregation errors has long been studied. Conversely, while examples of environmental toxins impacting fertility can be found throughout the literature, this field is only recently becoming a major focus of research. The studies done for this dissertation were done independently from one another and are presented here separately. The observation of hermaphroditic mice on the inbred strain A/HeJ prompted the investigation of the YA/HeJ chromosome. The YA/HeJ chromosome was transferred to the C57BL/6J background and the hermaphroditism trait segregated with it, indicating the two are linked. We found the YA/HeJ chromosome to be prone to missegregation, however, we did not find evidence that segregation errors cause the disturbances in sexual differentiation. Interestingly, we frequently observed a gap between YA/HeJ sister chromatids, indicating inappropriate centromere function. The mouse Y centromere is near the sex-determining genes and we hypothesize that a mutation(s) in this region affects both the YA/HeJ centromere (causing the gaps) and gene expression (causing the hermaphrodites). The YA/HeJ chromosome serves as a model to study centromere structure and function and, ultimately, what makes a chromosome prone to segregation error. After our laboratory relocated from Case Western Reserve University in Cleveland, Ohio, to Washington State University in Pullman, Washington, we experienced a significant decline in the reproductive fitness of our mouse colony. Pregnancy rates, egg and embryo quality, fetal development and pup survival were all negatively impacted. After investigating numerous environmental variables, we determined it was the facility-wide use of a quaternary ammonium disinfectant that was negatively affecting our mouse breeding colony. By eliminating the disinfectant from the facility and increasing the stringency of the automated cage washer, we were able to greatly improve the breeding performance of the mouse colony.
Patricia Hunt (Advisor)
111 p.
Biology, Genetics
CHROMOSOME; Centromere; YA/HeJ; C57BL/6J-YA/HeJ; BALB/cWt; Hermaphroditism; Disinfectants

Recommended Citations

Citations

  • Jackson, J. M. (2007). Investigation of Factors Affecting Fertility: Chromosome Segregation Errors and Environmental Toxins [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1181332723

    APA Style (7th edition)

  • Jackson, Jodi. Investigation of Factors Affecting Fertility: Chromosome Segregation Errors and Environmental Toxins. 2007. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1181332723.

    MLA Style (8th edition)

  • Jackson, Jodi. "Investigation of Factors Affecting Fertility: Chromosome Segregation Errors and Environmental Toxins." Doctoral dissertation, Case Western Reserve University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=case1181332723

    Chicago Manual of Style (17th edition)

case1181332723
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© 2007, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.