OP01.02: Unravelling the role of gestational melatonin supplementation: implications for neurodevelopment in an intrauterine growth‐restricted rabbit model

To assess the neuroprotective potential of melatonin (MEL) in an in vivo rabbit model of intrauterine growth restriction (IUGR). In pregnant rabbits, IUGR was induced by ligation of one uteroplacental vessel, with the other serving as a control. Mothers received oral placebo (PLA) or melatonin (MEL) from day 25 to 30 of gestation. On gestation day 30, the offspring were delivered by Caesarean section. Oligodendrocyte quantification, neuronal arborization assessment and DAB staining of melatonin receptors were performed. Differences between groups were assessed using ANOVA tests and multiple comparisons. Sixteen adult female rabbits and 116 pups were included in the experiment. A significant decrease in body weight in pups and percentage of survival were observed in IUGR groups in comparison to CNTs (48.6 vs 41.7, p < 0.001; 95.8% vs 73.5%, p < 0.021). Regarding brain analysis, although not significant, the number of oligodendrocytes was decreased in the IUGR group compared to CNT, but this effect was reverted in the IUGR treated with MEL (37.3 vs 48.1, p = 0.048). We found in neuronal area soma a difference between CNT and IUGR (355003 vs 257024, p < 0.001), which was improved by MEL treatment (355003 vs 299001, p = 0.018). Besides, a decrease in the primary dendrites length was observed in IUGR compared to CNT (225902 vs 164786, p = 0.050), which was improved in the MEL-treated group (225902 vs 190406, p = 0.353). Although not significant, a reduction on the melatonin receptors was observed in IUGR in comparison to CNT (4.81 vs 1.57, p < 0.018), with trends to be increased after MEL administration (4.81 vs 5.52, p = 0.200). MEL appears to have a neuroprotective role by quantitively and morphologically improving brain cells in IUGR. These findings highlight the need for further investigation to elucidate the underlying mechanisms.