Prolonged exposure to rosuvastatin from pre-puberty to adulthood impairs sperm quality in mice and leads to paternally mediated developmental toxicity.

Autor: de Mello TF; Laboratório de Reprodução e Toxicologia (Laretox), Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil; Programa de Pós-graduação em Biologia Celular e do Desenvolvimento, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: tai.mello.f@gmail.com., Goedert AB; Laboratório de Reprodução e Toxicologia (Laretox), Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: aabgoedert@gmail.com., de Souza JSS; Laboratório de Reprodução e Toxicologia (Laretox), Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: juliaschubert20@gmail.com., da Cruz JVR; Laboratório de Reprodução e Toxicologia (Laretox), Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: ramoss.cruzz.27@gmail.com., da Silva AS; Laboratório de Reprodução e Toxicologia (Laretox), Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil; Programa de Pós-graduação em Biologia Celular e do Desenvolvimento, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: silvaalicesantosa@gmail.com., Knorst JK; Laboratório de Reprodução e Toxicologia (Laretox), Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: knorst965@gmail.com., Muller YMR; Programa de Pós-graduação em Biologia Celular e do Desenvolvimento, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: yararauh@gmail.com., Silva FRMB; Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: mena.barreto@ufsc.br., Leite GAA; Laboratório de Reprodução e Toxicologia (Laretox), Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil; Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: gabriel.leite@ufsc.br.
Jazyk: angličtina
Zdroj: Reproductive toxicology (Elmsford, N.Y.) [Reprod Toxicol] 2024 Sep 12; Vol. 130, pp. 108717. Date of Electronic Publication: 2024 Sep 12.
DOI: 10.1016/j.reprotox.2024.108717
Abstrakt: Nowadays, changes in human lifestyle have increased dyslipidemia, reinforcing the necessity of using lipid-lowering drugs, such as statins, to control the lipid profile. Among the statins, rosuvastatin has shown greater efficacy in controlling dyslipidemia. Previous studies have shown adverse effects in adult men and pre-pubertal rodents after exposure to statins, such as reduced testosterone levels and delayed puberty. This study aimed to evaluate the reproductive parameters and fertility of male mice exposed to rosuvastatin from pre-puberty to sexual maturity by simulating human chronic exposure to rosuvastatin from pre-puberty to adulthood. This is the first study to evaluate male reproduction and developmental outcomes after prolonged rosuvastatin exposure since pre-puberty, mimicking the human exposure to relevant doses of the drug. Then, we hypothesize that prolonged exposure to rosuvastatin since pre-puberty may impair reproductive parameters in males and generate paternally mediated developmental toxicity. Male mice were divided into three experimental groups that received a 0.9 % saline solution, 1.5 or 5.5 mg/kg/day of rosuvastatin, by intragastric oral gavage, from postnatal day (PND) 23 to PND 80. Puberty onset was delayed and sperm quality was reduced in both rosuvastatin-treated groups. Furthermore, testicular interstitial tissue showed increased vascularization in a dose-dependent manner. After mating with non-treated females, the post-implantation loss rate increased in both rosuvastatin-exposed groups. There was an increase in the percentage of fetuses with opened eyelids in the offspring of males exposed to 1.5 mg/kg/day of the statin and a decrease in the craniocaudal distance of male offspring from males exposed to the higher dose. In summary, our hypothesis that rosuvastatin exposure would cause male reproductive toxicity and developmental impairment in the offspring of male mice was confirmed. This study raises concerns about the reproductive health of men who take this medication from infancy until adulthood in prolonged treatment.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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