Docosahexaenoic Acid and Lactoferrin Effects on the Brain and Placenta in a Rabbit Model of Intrauterine Growth Restriction 

Abstract

Intrauterine growth restriction (IUGR) is associated with suboptimal perinatal outcomes and neurodevelopment in the offspring. We hypothesize that prenatal supplementation with docosahexaenoic acid (DHA) or lactoferrin (Lf) would ameliorate these consequences. At 25 days of gestation, IUGR was surgically induced in pregnant rabbits, which were randomized as follows: no treatment, or DHA or Lf administration. DHA or Lf were administrated orally once per day. Five days later, animals were delivered obtaining controls, untreated IUGR, IUGR treated with DHA and IUGR treated with Lf, and the associated placentas. At postnatal day 1, a functional evaluation was performed and, thereafter, brains were obtained. Neuronal arborization in the prefrontal cortex and the density of pre-oligodendrocytes in the corpus callosum were then evaluated. Untreated IUGR pups presented a higher percentage of stillbirth, lower birth weight, and poorer neurobehavioral performance in comparison with control pups, and these are associated with structural changes in brain and placenta. Regarding treated IUGR animals, although no significant improvements were detected in perinatal data, functional and structural effects were observed in either the brain or the placenta. DHA and Lf supplements in a rabbit model of IUGR were related to neurodevelopmental improvements and an amelioration of the placental changes.

Lactoferrin/sialic acid prevents adverse effects of intrauterine growth restriction on neurite length: investigations in an in vitro rabbit neurosphere model

“…In previous in vivo experiments using the same rabbit model, IUGR animals did not present severe functional impairments at short-term (PND1) (Pla et al, 2020), but only at later time points (PND70) neurobehavioral and cognitive deficiencies could be evaluated and indeed memory and anxiety traits were detected in the IUGR animals (Illa et al, 2013(Illa et al, , 2018. In future, we need studies evaluating long-term effects of LF in GM along with cognitive functional studies, which could not be assessed at the short-term evaluation in our animal species (Illa et al, 2023).…”