What lessons have we learnt about the impact of maternal cigarette smoking from animal models?

Maternal first- or second-hand tobacco smoking during pregnancy is still common albeit that the detrimental effects to the unborn child are well known. Maternal tobacco cigarette smoking can affect multiple organ systems in the offspring, rendering them at increased risk of various conditions throughout life (eg. intrauterine underdevelopment, asthma, substance abuse, diabetes). However, this review will only focus on its impact on the brain and the related molecular changes in the offspring based on evidence from animal studies. Although epidemiological studies have identified the associations between maternal cigarette smoke exposure (SE) and brain disorders, animal models can help identify the underlying mechanisms and test interventions. Human studies have found that maternal SE is closely linked to small brain size and changes in brain structure and associated with a high risk of cognitive defects. Animal models suggest that this may be due to increased brain oxidative stress and inflammation during the neonatal period, leading to increased brain cell apoptosis in adulthood. There is a distinct gender bias of such impacts, where male offspring are more affected than females. Female offspring seem to have developed the adaptation by increasing endogenous antioxidant levels. Indeed, animal studies have shown that using antioxidant supplementation during pregnancy can improve neurological outcomes in male offspring, however, the efficacy in humans is yet to be confirmed. Furthermore, some animal studies suggested nicotine as the key player in intrauterine underdevelopment due to maternal SE, while human clinical trials using nicotine replacement therapy do not support this mechanism. This review will discuss the possible reasons.