RESUMEN
This study was conducted to evaluate the effects of ivermectin (IVM) with therapeutic dose (injected with 0.56 mg/kg b.wt.) either alone or combined with alpha lipoic acid (ALA) (50 mg/kg b.wt daily) on expression of testicular insulin-like growth factor binding protein-3 (IGFBP-3) and heat-shock protein A1 (HSPA1)) genes in the testes, as well as on male rat fertility parameters. Results revealed that expression levels of IGFBP-3 and HSPA1 were significantly increased in testis of the IVM-treated group relative to the control group. Furthermore, injection of ivermectin showed a significant decrease in serum testosterone level, sperm count, motility %, live sperm% and index weight of reproductive organs, and a significant increase in sperm abnormalities. Moreover, IVM induced oxidative stress and pathological alterations in the testes. Meanwhile, the administration of ALA with IVM prevented testicular damage and improved all previous parameters. We concluded that ivermectin has undesirable effects on male fertility and altered expression of IGFBP-3 and HSPA1 genes in the testes, while the administration of alpha lipoic acid can ameliorate the adverse effects of ivermectin.
Asunto(s)
Fertilidad/efectos de los fármacos , Proteínas HSP70 de Choque Térmico/metabolismo , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Ivermectina/farmacología , Testículo/efectos de los fármacos , Ácido Tióctico/farmacología , Animales , Proteínas HSP70 de Choque Térmico/genética , Infertilidad Masculina/genética , Infertilidad Masculina/metabolismo , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Testículo/metabolismoRESUMEN
MicroRNAs (miRNAs) are small endogenous molecules that are involved in a diverse of cellular process. However, little is known about their abundance in bovine oocytes and their surrounding cumulus cells during oocyte development. To elucidate this situation, we investigated the relative expression pattern of sets of miRNAs between bovine oocyte and the surrounding cumulus cells during in vitro maturation using miRNA polymerase chain reaction (PCR) array. Results revealed that a total of 47 and 51 miRNAs were highly abundant in immature and matured oocytes, respectively, compared with their surrounding cumulus cells. Furthermore, expression analysis of six miRNAs enriched in oocyte miR-205, miR-150, miR-122, miR-96, miR-146a and miR-146b-5p at different maturation times showed a dramatic decrease in abundance from 0 h to 22 h of maturation. The expression of the same miRNAs in preimplantation stage embryos was found to be highly abundant in early stages of embryo development and decreased after the 8-cell stage to the blastocyst stage following a typical maternal transcript profile. Similar results were obtained by localization of miR-205 in preimplantation stage embryos, in which signals were higher up to the 4-cell stage and reduced thereafter. miR-205 and miR-210 were localized in situ in ovarian follicles and revealed a spatio-temporal expression during follicular development. Interestingly, the presence or absence of oocytes or cumulus cells during maturation was found to affect the expression of miRNAs in each of the two cell types. Hence, our results showed the presence of distinct sets of miRNAs in oocytes or cumulus cells and the presence of their dynamic degradation during bovine oocyte maturation.