RESUMO
Carbamazepine (CBZ) is used in the control of seizure and affective disorders, causing hypothyroidism. Thyroid hormones regulate the Sertoli cell proliferation and differentiation. Clinical aspects must be considered since epileptic fertile women need to continuously use CBZ during pregnancy and lactation. This study aimed to evaluate the effects of CBZ on testis development of rat offspring from dams treated during pregnancy/lactation. Rat dams received CBZ (20 mg kg-1 day-1 ) or vehicle by intra-peritoneal route during gestation and lactation. Progenies were euthanised at 4, 14, 41, 63 and 93-days post-partum (dpp) for the evaluation of T3, T4 and TSH plasma total levels. Testicular cross sections were submitted to anti-Ki67, anti-PCNA, anti-p27kip1 and anti-transferrin immunolabelling for the evaluation of Sertoli cells. There was a significant reduction in p27kip1 -positive Sertoli cell numerical densities and an increase in TSH level at 14 dpp. CBZ exposure affected the volume density of transferrin-positive immunolabelling at 63 dpp. These results suggest that CBZ may cause a dysregulation of the controller system of thyroid hormones homeostasis leading to an increase in the proliferation rate at the neonatal phase and a differentiation delay of the Sertoli cell, culminating in an altered function at late puberty. The occurrence of hypothyroidism cannot be completely discarded.
Assuntos
Carbamazepina , Hormônios Tireóideos , Animais , Carbamazepina/toxicidade , Diferenciação Celular , Proliferação de Células , Feminino , Lactação , Masculino , Gravidez , Ratos , Células de SertoliRESUMO
BACKGROUND: In the coming decades, diabetes mellitus might affect 628 million individuals. Its final impact on male fertility and reproductive outcomes should be considered since the number of adolescents and young adults presenting diabetes is rising. Resveratrol (RES), a polyphenol, is a biological modulator with multitarget and multi-action characteristics. OBJECTIVES: to evaluate if RES is effective against the male reproductive damage caused by type 1 diabetes (DM1), focusing on sperm DNA integrity and reproductive outcome. MATERIALS AND METHODS: At 30 dpp (days postpartum), male rats were divided into 7 groups: Sham control (SC); RES vehicle (RV); RES (R); STZ-diabetic (D; induced at 30dpp with 65 mg/kg of streptozotocin); STZ-diabetic + insulin (DI); STZ-diabetic + RES (DR); STZ-diabetic + insulin +RES (DIR). DR, DIR, and R groups received 150mg RES/kg b.w./day by gavage (from 33 to 110dpp). DI and DIR received insulin (from day 5 after DM1 induction until 110dpp). Blood glucose was monitored in different time points. Animals were mated with healthy females. Euthanasia occurred at 110 dpp. RESULTS: DM1 increased lipid peroxidation (testis and epididymis) and sperm DNA fragmentation, alterations of chromatin structure, reduced mitochondrial mass and acrosome integrity, causing a decline in fertility and pregnancy rates. RES improved the parameters. DISCUSSION: RES, as an adjuvant, activates specific reactions against hyperglycemia, the main trigger of most complications of diabetes, by controlling oxidative stress, probably as a result of SIRT1 activation. We present here more evidences showing its valuable role in diminishing diabetes seriousness to male reproduction, not only to spermatogenesis in the first instance, but also to sperm overall quality and fertility outcomes, regardless of insulin treatment. CONCLUSION: RES attenuated lipid peroxidation and sperm DNA damage in DM1-induced animals, which positively reflected on male fertility. Our results show RES potential against DM1 complications in male reproduction.