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Year:: 2018
Contributor:: Clark, Haley (Creator); Brayboy, Lynae (advisor); Freiman, Richard (reader); Brown University (sponsor)
Genre:: theses
Subject:: mitophagy; transgenerational; mitochondria; Nitrogen mustards
Extent:: 30 p.
DOI: https://doi.org/10.26300/ckgx-8270

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Abstract:: Nitrogen Mustard (NM) is an alkylating chemical warfare agent that poses an international threat in the possession of ISIS. Other alkylating agents and chemotherapeutic derivatives of NM have been shown to result in decreased ovarian reserve and sometimes ovarian failure. Alkylating agents have also been shown to result in mitochondrial dysfunction associated with ROS dependent oxidative stress. Mitochondrial inheritance is entirely maternal, so mothers exposed to NM face the risk of passing down damaged mitochondria in their oocytes to their children, as oocytes do not allow for the destruction of damaged oocytes through mitophagy. Therefore, the objective of this study is to investigate the effects of NM on ovarian and oocyte mitochondria, as well as the transgenerational transmission of these effects, in order to characterize the occupational risks facing female soldiers, veterans, and their future children. Ovaries and oocytes of mice treated with 0.1mg/kg NM were observed for oxidative stress, morphology of mitochondrial, abundance of mitophagy proteins, and ATP production. Mice were also mated to F1 and F2 generations to determine reproductive and molecular transgenerational outcomes of NM-exposure. NM was correlated to an increase in oxidative stress that is transmitted to F1 generation, decreased mitochondrial volume and increased abundance of unidentified electron dense structures in ovaries, potential initiation of mitophagy in ovaries, and lower birth weight of pups born to NM-exposed mothers. Further investigation is needed so that female soldiers, veterans, and cancer patients may be adequately counseled about their long-term risks, as well as those facing their future children.
Notes:: Senior thesis (AB)--Brown University, 2018; Concentration: Biology, Physiology, and Biotechnology

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Rights: In Copyright
Restrictions on Use: Collection is open for research.

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Clark, Haley, "Transgenerational Effects of Nitrogen Mustard Exposure, and Reproductive Outcomes" (2018). Biology and Medicine Theses and Dissertations, Molecular Pharmacology, Physiology, and Biotechnology Theses and Dissertations. Brown Digital Repository. Brown University Library. https://doi.org/10.26300/ckgx-8270

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Theses and Dissertations for the Molecular Pharmacology, Physiology, and Biotechnology department.
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Transgenerational Effects of Nitrogen Mustard Exposure, and Reproductive Outcomes