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Influence of the AT1 Receptor Antagonists Telmisartan and Losartan on Reproduction and Offspring After Paternal Exposure to Ionizing Radiation

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Abstract

This study evaluated the repercussions of paternal exposure to radiation on reproduction and offspring in rats, as well as whether treatment with the angiotensin II type 1 (AT1) receptor antagonists telmisartan and losartan has a mitigating effect. Rats were randomly divided into 6 groups: control, radiation, telmisartan, losartan, radiation + telmisartan, and radiation + losartan. A single 5 Gy dose of radiation was administered directly into the scrotum, followed by treatment with telmisartan (12 mg/kg/d) or losartan (34 mg/kg/2 times per day) for 60 days in the groups receiving these medications. The reproductive ability of the test animals was assessed before and after exposure to radiation via fertility tests. The resulting offspring were analyzed for the presence of external and internal anomalies. Ionizing radiation significantly affected the rates of fertility, pre- and postimplantation losses, and implantation. Telmisartan and losartan did not significantly prevent this radiation-induced damage. The frequency of fetal anomalies was similar in offspring produced before and after paternal radiation exposure. Moreover, irradiated rats that received treatments and were able to generate offspring did not produce fetuses with morphological changes; this may represent a possible radioprotective effect AT1 antagonists have on offspring development, although few fetuses survived and were evaluated for malformations. Although the study findings indicate that these medications have a positive effect, further studies with longer treatment periods (extending beyond 1 rat spermatogenic cycle) are needed to determine whether these drugs significantly improve reproductive rates after paternal exposure to radiation, which may also reflect an increase in the number of viable fetuses.

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Authors and Affiliations

  1. Department of Human Embryology, Marília Medical School, Avenida Monte Carmelo, 800, Fragata, CEP: 17.519-030 CP: 2003, Marília, São Paulo, Brazil

    Ana Paula Cavalim Vale, Guilherme dos Santos & Maria Angélica Spadella PhD

  2. Human Anatomy Laboratory, Marília Medical School, Marília, São Paulo, Brazil

    Teresa Prado da Silva PhD

  3. Department of Anatomy, Institute of Biomedical Sciences University of São Paulo, São Paulo, Brazil

    Naira Silva da Mansano PhD

  4. Laboratory of Pharmacology, Marília Medical School, Marília, São Paulo, Brazil

    Agnaldo Bruno Chies PhD

  5. Human Development and Technology, University of Marília, São Paulo, Brazil

    Eduardo Federighi Baisi Chagas PhD

Authors
  1. Ana Paula Cavalim Vale
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  2. Guilherme dos Santos
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  3. Teresa Prado da Silva PhD
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  4. Naira Silva da Mansano PhD
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  7. Maria Angélica Spadella PhD
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Correspondence to Maria Angélica Spadella PhD.

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Vale, A.P.C., dos Santos, G., da Silva, T.P. et al. Influence of the AT1 Receptor Antagonists Telmisartan and Losartan on Reproduction and Offspring After Paternal Exposure to Ionizing Radiation. Reprod. Sci. 26, 639–648 (2019). https://doi.org/10.1177/1933719118783251

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  • DOI: https://doi.org/10.1177/1933719118783251

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