Original Article Influence of the AT1 Receptor Antagonists Telmisartan and Losartan on Reproduction and Offspring After Paternal Exposure to Ionizing Radiation Ana Paula Cavalim Vale 1 , Guilherme dos Santos 1 , Teresa Prado da Silva, PhD 2 , Naira da Silva Mansano, PhD 3 , Agnaldo Bruno Chies, PhD 4 , Eduardo Federighi Baisi Chagas, PhD 5 , and Maria Ange ´ lica Spadella, PhD 6 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 þ telmisartan, and radiation þ 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 implan- tation. 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. Keywords ionizing radiation, oxidative stress, male reproductive system, fetal development, radiation-induced abnormalities Introduction Radiation therapy is one of the main sources of human expo- sure to ionizing radiation. Although it may boost survival in patients with cancer by healing or controlling tumors, this ther- apy modality can also damage healthy tissues and leave long- term sequelae. 1-3 Ionizing radiation causes damage to living tissues through a series of primary and secondary molecular events. The direct effects can occur from the interaction between radiation and essential macromolecules such as DNA, which is the main target of radiation because of its role in controlling cellular functions. Ionizing radiation also leads indirectly to tissue inju- ries through the radiolysis of water, generating free radicals such as superoxide anions, hydrogen peroxide, and hydroxyl radicals. These free radicals react with cellular macromole- cules such as DNA, RNA, and proteins, causing cellular dys- function or death from oxidative stress. 4-7 Oxidative stress caused by radiation is an important factor in the etiology of male infertility. 1,7-9 In the testis of humans as well as other animal species, radiation particularly affects the 1 Marı ´lia Medical School, Marı ´lia, Sa ˜o Paulo, Brazil 2 Human Anatomy Laboratory, Marı ´lia Medical School, Marı ´lia, Sa ˜o Paulo, Brazil 3 Department of Anatomy, Institute of Biomedical Sciences, University of Sa ˜o Paulo, Sa ˜o Paulo, Brazil 4 Laboratory of Pharmacology, Marı ´lia Medical School, Marı ´lia, Sa ˜o Paulo, Brazil 5 Human Development and Technology, University of Marı ´lia, Sa ˜o Paulo, Brazil 6 Human Embryology Laboratory, Marı ´lia Medical School, Marı ´lia, Sa ˜o Paulo, Brazil Corresponding Author: Maria Ange ´lica Spadella, Department of Human Embryology, Marı ´lia Medical School, Avenida Monte Carmelo, 800, Fragata, CEP: 17.519-030 CP: 2003, Marı ´lia, Sa ˜o Paulo, Brazil. Email: maspadella@gmail.com Reproductive Sciences 2019, Vol. 26(5) 639-648 ª The Author(s) 2018 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/1933719118783251 journals.sagepub.com/home/rsx