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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: REPRODUCTIVE SCIENCES; v. 26, n. 5, p. 639-648, MAY 2019.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 15/20740-4 - Action of AT1 receptor antagonists in the mitigation of structural and functional damage in reproductive tissue of rats exposed to ionizing radiation
• Grantee: Maria Angélica Spadella Santos
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/11531-8 - Evaluation of the skeletal and visceral development of the offspring of male rats irradiated and treated with inhibitors of the renin-angiotensin system
• Grantee: Guilherme dos Santos
• Support Opportunities: Scholarships in Brazil - Scientific Initiation