Administração de cafeína durante a gestação altera parâmetros testiculares na prole de camundongos C57/BL6 na vida adulta

Abstract

Active metabolites of caffeine present toxicity, may cause deleterious effects on many organs in the fetal period by maternal consumption. This study aimed to evaluate the role of caffeine administration during pregnancy on several parameters of adult male testis in C57BL/6 mice. Pregnant C57BL/6 female mice were divided into two groups (n = 10): Control group (C), dams were injected with the vehicle only (saline 0.9 % NaCl); Caffeine group (CF), dams received daily a subcutaneous injection of 20 mg/kg of caffeine/day (1 mg/mL saline). Pups had free access to standard chow since weaning to 3 months of age, when they were killed. Treatment of dams with caffeine did not produce any visible signs of maternal toxicity. At adulthood CF group presented a reduction in the food consumption (C = 4.36 ± 0.14, CF = 3.79 ± 0.05/g, p<0.05) and body weight gain (C = 25.73 ± 0.14, CF = 21.08 ± 0.41/ g, p=0.0001). Several alterations were seen in testis structure sighted by morphometry: testicular weight (C = 0.078 ± 0.003, CF = 0.063 ± 0.002/g, p=0.002), tubular diameter (C = 455.4 ± 2.7, CF = 393.5 ± 3.1/µm, p=0.0001), tubular lumen (C = 310.6 ± 2.5, CF = 254.8 ± 2.9/µm², p=0.0001) and epithelial height (C = 144.8 ± 0.9; CF = 138.7 ± 1.3/µm, p=0.0005). Chemioluminesense was performed to evaluate testosterone serum levels, which was decreased (C = 6.6 ± 2.8, CF = 0.5 ± 0.2/ng/ml, p=0.04). Western blotting showed an increase in the protein expression of leptin s receptor (C = 0.81 ± 0.04, CF = 1.28 ± 0.15/µg, p=0.02), luteinizing hormone receptor (C = 0.92 ± 0.05, CF = 0.74 ± 0.05/µg, p=0.01), aromatase (C = 0.32 ± 0.03, CF = 0.48 ± 0.05/µg, p=0.03) and apoptose proteins (C = 0.27 ± 0.02; CF = 0.42 ± 0.03/µg, p=0.002), while follicle stimulant hormone receptor (C = 0.76 ± 0.06, CF = 0.56 ± 0.04/µg, p=0.02), steroidogenesis protein receptor (C = 1.009 ± 0.065, CF = 0.584 ± 0.060/µg, p=0.0007), vascular-endotelial growth factor (C = 0.33 ± 0.08, CF = 0.05 ± 0.01/µg, p=0.009), androgen receptor (C = 0.97 ± 0.11, CF = 0.59 ± 0.07/µg, p=0.02) and proliferating cell nuclear antigen (C = 0.93 ± 0.11; CF = 0.48 ± 0.07/µg, p=0.01) were reduced by maternal caffeine treatment. This study suggests that caffeine consumption during pregnancy appears to be detrimental to fertility in male offspring, by testicular programming, which generates disturbances in testicular function.