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

被引:5
作者
Cavalim Vale, Ana Paula [1 ]
dos Santos, Guilherme [1 ]
da Silva, Teresa Prado [2 ]
Mansano, Naira da Silva [3 ]
Chies, Agnaldo Bruno [4 ]
Baisi Chagas, Eduardo Federighi [5 ]
Spadella, Maria Angelica [6 ]
机构
[1] Marilia Med Sch, Marilia, SP, Brazil
[2] Marilia Med Sch, Human Anat Lab, Marilia, SP, Brazil
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Sao Paulo, SP, Brazil
[4] Marilia Med Sch, Lab Pharmacol, Marilia, SP, Brazil
[5] Univ Marilia, Human Dev & Technol, Marilia, SP, Brazil
[6] Marilia Med Sch, Human Embryol Lab, Marilia, SP, Brazil
基金
巴西圣保罗研究基金会;
关键词
ionizing radiation; oxidative stress; male reproductive system; fetal development; radiation-induced abnormalities; ANGIOTENSIN-CONVERTING ENZYME; SYSTEM; SPERMATOGENESIS; EXPRESSION; TOXICITY; CANCER; TESTES; MICE;
D O I
10.1177/1933719118783251
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
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.
引用
收藏
页码:639 / 648
页数:10
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