RESUMO
Caffeine is commonly consumed by pregnant women to avoid fatigue or as a habit. However, it is not clearly determined its side effects to the conceptuses. This study evaluated placental morphofunctional alterations after maternal chronic caffeine intake and the effects on fetal growth. Female Swiss mice received, via gavage, caffeine doses (either 60, 120 or 240 mg/kg/day) seven days before mating until gestational days-(GD) 11.5 or 17.5. Fetal biometrical parameters were assessed, and placentae were either submitted to histomorphometrical or molecular evaluation of angiogenesis (placental growth factor-1[PlGF-1]), apoptosis (Caspase-3) and proliferation (Ki-67) markers (evaluated in Swiss dams) and to intravital microscopy (evaluated in C57BL/6 dams). Caffeine exposed fetuses exhibited intrauterine growth restriction in a sex-dependent manner, with greater commitment of female fetuses (P < 0.05). In addition, placentae from dams that received 120 mg/kg/day showed less irrigation by maternal blood and greater development of fetal vasculature, characterized by higher number of larger vessels (P < 0.05). Although no effects on apoptosis (Caspase-3) and angiogenesis (PlGF-1) were observed, dams treated with 60 mg/kg/day showed greater placental cell proliferation (Ki-67 staining) at GD 11.5 (P < 0.05). The group treated with 240 mg/kg/day exhibited only one pregnant dam for each gestational age, suggesting that this high caffeine consumption may compromise fertility. Taken together, even in the doses currently ingested by many pregnant women, caffeine has detrimental effects on placental vasculature and fetal development in mice. Therefore, our results strongly suggest that caffeine consumption in human pregnancies greater than the recommended doses should be avoided.
RESUMO
Intrauterine growth restriction (IUGR) compromises fetal development, leading to low birth weight, and predisposes to gastrointestinal disorders. Pigs that suffered IUGR present poor postnatal development, resulting in great economic losses to the industry. The small intestine may be involved with impaired development, but studies investigating this issue are still limited. Thus, the present study aimed to investigate small intestine morphofunctional alterations in IUGR pigs throughout the production phases (birth to 150 days). IUGR pigs presented lower body weight from birth to the finishing phase (P < 0.05). Although histomorphometrical parameters were not affected during the pre-weaning period, their commitment was observed specifically in the duodenum of the IUGR group at older ages (P < 0.05). The most detrimental effects on the small intestine, such as deeper duodenum crypts' depth, lower villus height:crypt depth ratio and absorptive area, increased apoptosis and lower proliferation of the duodenum epithelium were noticed at 70 days of age (P < 0.05). Additionally, IUGR pigs presented the lowest chymotrypsin and amylase activities at 70 and 150 days of age, respectively (P < 0.05). These findings may contribute to the elucidation of morphofunctional disorders of the small intestine in IUGR pigs throughout the different production phases, suggesting that poor postnatal development may be due to intestinal damage.
