Gestational caffeine exposure acts as a fetal thyroid-cytokine disruptor by activating caspase-3/BAX/Bcl-2/Cox2/NF-κB at ED 20
The objective of this examination was to explore the impact of gestational caffeine (1,3,7-trimethylxanthine) exposure on the maternofetal thyroid axis and fetal thyroid–cytokine communications during gestation. Pregnant rats (Rattus norvegicus) were intraperitoneally administered caffeine (120 or 150 mg kg−1) from gestation day (GD) 1 to 20. Both doses of caffeine resulted in maternal hyperthyroidism, whereas the elevation in the concentration of serum free triiodothyronine (FT3) and free thyroxine (FT4) was related to a depletion in the level of TSH at GD 20. Maternal body weight gain and food consumption were markedly increased, while fetal body weight was significantly reduced. These alterations caused fetal hypothyroidism and several pathological lesions in the fetal thyroid gland including a vacuolar colloid, destructive degeneration, atrophy and hyperplasia at embryonic day (ED) 20. The abnormalities in the fetal thyroid gland seemed to depend on the activation of caspase-3, Bcl-2, BAX, Cox2, and NF-κB mRNA expression. Both maternal caffeine doses caused a marked attenuation in the values of fetal serum GH, IGF-II, VEGF, TGF-β, TNF-α, IL-1β, IL-6, leptin and MCP-1, and a noticeable elevation in the value of fetal serum adiponectin at ED 20. Thus, gestational caffeine exposure might disrupt the fetal thyroid–cytokine axis.