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IDENTIFICATION AND CHARACTERIZATION OF ESTROGEN-MEDIATED EFFECTS ON FEMALE MEIOSIS: STUDIES OF BISPHENOL A AND ESTROGEN RECEPTORS

Susiarjo, Martha
http://rave.ohiolink.edu/etdc/view?acc_num=case1158685403

Abstract Details

2007, Doctor of Philosophy, Case Western Reserve University, Genetics.
The meiotic process in female mammals is unique: Oocytes initiate the prophase events of pairing, synapsis, and recombination during fetal development, arrest at late prophase around birth, and resume and complete the first meiotic division prior to ovulation, years or decades later. This process requires a complex coordination of genetic factors and is responsive to environmental influences. During the course of meiotic studies in our laboratory, we have uncovered estrogenic effects at different stages of oocyte development. Fetal exposure to the environmental estrogen bisphenol A (BPA) impairs synapsis and recombination in the developing oocyte. These prophase defects are correlated with increased aneuploidy in oocytes and embryos from adult females exposed in utero. To study the mechanism of action of BPA, we have analyzed mice lacking the two known estrogen receptors (ERs), ER alpha and ER beta. The phenotype of ER beta null females is identical to BPA-exposed females, suggesting that BPA acts by disrupting ER beta-mediated effects in the developing ovary. Our data implicate a role of ER beta-mediated estrogen action at the onset of oocyte development, at a time when the oocyte is not yet enclosed in the primordial follicle. Lack of ER beta in the developing fetal ovary profoundly compromises the genetic quality of oocytes. Additionally, ER beta mediates estrogen action during the late stage of oocyte growth, as our preliminary data demonstrate that absence or reduced levels of ER beta increases the level of aneuploidy by disrupting metaphase events. In summary, this thesis presents evidence that estrogen plays critical roles during the early and late stages of oocyte development, and demonstrates that exposure to estrogenic substances during the fetal or postnatal development can profoundly affect the genetic quality of the oocyte.
Patricia Hunt (Advisor)
128 p.
Biology, Genetics
OOCYTES; BPA; ER¿¿¿¿; Meiotic; ESTROGEN; Follicle; Aneuploidy

Recommended Citations

Citations

  • Susiarjo, M. (2007). IDENTIFICATION AND CHARACTERIZATION OF ESTROGEN-MEDIATED EFFECTS ON FEMALE MEIOSIS: STUDIES OF BISPHENOL A AND ESTROGEN RECEPTORS [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1158685403

    APA Style (7th edition)

  • Susiarjo, Martha. IDENTIFICATION AND CHARACTERIZATION OF ESTROGEN-MEDIATED EFFECTS ON FEMALE MEIOSIS: STUDIES OF BISPHENOL A AND ESTROGEN RECEPTORS. 2007. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1158685403.

    MLA Style (8th edition)

  • Susiarjo, Martha. "IDENTIFICATION AND CHARACTERIZATION OF ESTROGEN-MEDIATED EFFECTS ON FEMALE MEIOSIS: STUDIES OF BISPHENOL A AND ESTROGEN RECEPTORS." Doctoral dissertation, Case Western Reserve University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=case1158685403

    Chicago Manual of Style (17th edition)

case1158685403
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© 2006, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.