Task Progress:
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Aim 1: Acute exposure to low dose HZE particles induces uterine oxidative stress and alters pregnancy outcomes. Three-month-old female mice (C57BL/6J from Jackson Labs) were exposed to low dose (0 and 50 cGy; n=8/treatment) iron (LET = 179 KeV/µm) at an energy of 600 MeV/u. Two groups were irradiated at the highest dose for each of the two charged particles, one fed AIN-93M chow and the other fed the same chow supplemented with 150 mg/kg chow of the antioxidant alpha lipoic acid. Uteri were collected at 6 h, 1 wk, and 8 wks after irradiation. At 6 h and 1 wk time point, mice were sacrificed without knowing the stage of the estrous cycle. At 8 wks time-point, mice were sacrificed at the metestrus stage of the cycle to avoid cycle-stage related variations in reproductive hormones. To understand the effects of charged particles radiation on the uterus, average uterine weight at 6 h, 1wk, and 8wks after IR were analyzed. Average uterine weight remained unchanged among the treatment at 6 h, 1 wk, and 8 wks after radiation suggesting that charged particle exposure does not effect on uterine mass. To understand the acute effects of charged particles radiation on the uterus, uterine histomorphology was analyzed using H&E stained slides. At 6 h and 1 wks, uterine morphology was normal among the treatment, but it was quite abnormal at 8 wks after radiation. Most importantly, the luminal epithelial layer had decreased the number of epithelial cells, and many of them had an abnormal shape. Furthermore, the number of uterine glands were significantly decreased, and the number of cystic glands was decreased in 50 cGy irradiated mice compared to control. To delineate the primary mechanism involved in the damage of uterine lumen, the DNA double-strand breaks in the luminal epithelial were analyzed using gH2AX immunostaining. Histone 2Ax protein gets phosphorylated in response to DNA double-strand breaks. Percentage of gH2AX was significantly higher in 50 cGy treated mice compared to control. The mice supplemented with alpha lipoic acid along with 50 cGy had similar uterine morphology and gH2AX immunostaining as seen for 50 cGy iron alone.
Aim 2: Exposure to charged particles causes uterine cancer. Three-month-old female mice of two strains, one thought to be sensitive to radiation-induced tumors (B6C3F1) and one thought to be less sensitive to radiation-induced tumors (C57BL/6J) were exposed to low dose (0 and 50 cGy; n=15/treatment) iron (LET = 179 keV/µm) and aged to 18 months. Uteri were collected at 15 months after irradiation. These tissues were fixed with 4% PFA or 10% Formalin for histomorphology and immunohistochemistry analysis. At 15 months after radiation, average uterine weight was significantly decreased in 50 cGy treated mice (108.8±31.6 mg) compare to control (198±50.8 mg) in both strains of mice.
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Bibliography Type:
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Description: (Last Updated: 06/22/2020)
Show Cumulative Bibliography Listing
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Abstracts for Journals and Proceedings
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Mishra B, Ortiz L, Luderer U. "Space radiation causes premature ovarian failure and epithelial ovarian tumors in mice." 2016 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 8-11, 2016. 2016 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 8-11, 2016. , Feb-2016
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Abstracts for Journals and Proceedings
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Mishra B., Ripperdan R, Ortiz L, Luderer U. "Charged iron particles, components of space radiation, cause premature ovarian failure and epithelial ovarian tumors in mice." Systems Biology of Reproduction SSR 49th Annual Meeting, San Diego, CA, July 16-20, 2016. Systems Biology of Reproduction SSR 49th Annual Meeting, San Diego, CA, July 16-20, 2016. , Jul-2016
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Articles in Peer-reviewed Journals
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Mishra B, Ortiz L, Luderer U. "Charged iron particles, components of space radiation, destroy ovarian follicles." Human Reproduction. 2016 Aug;31(8):1816-26. http://dx.doi.org/10.1093/humrep/dew126 ; PubMed PMID: 27251203; PubMed Central PMCID: PMC4974665 , Aug-2016
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Articles in Peer-reviewed Journals
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Mishra B, Ripperdan R, Ortiz L, Luderer U. "Very low doses of heavy oxygen ion radiation induce premature ovarian failure." Reproduction. 2017 Aug;154(2):123-33. https://doi.org/10.1530/REP-17-0101 ; PMID: 28528322; PMCID: PMC5598766 , Aug-2017
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Articles in Peer-reviewed Journals
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Mishra B, Lawson GW, Ripperdan R, Ortiz L, Luderer U. "Charged-iron-particles found in galactic cosmic rays are potent inducers of epithelial ovarian tumors." Radiat Res. 2018 Aug;190(2):142-50. https://doi.org/10.1667/RR15028.1 ; PMID: 29781764; PMCID: PMC6112765. , Aug-2018
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Awards
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Mishra B. "Systems Biology of Reproduction SSR 49th Annual Meeting, Larry Ewing Memorial Trainee Travel Fund Award, July 2016." Jul-2016
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Awards
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Mishra B. "School of Medicine, University of California Irvine Travel award, July 2016." Jul-2016
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Awards
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Mishra B. "University of California Irvine Postdoctoral Scholar Symposium Poster competition: Second place, September 2016." Sep-2016
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