Does Antenatal Lactoferrin Protect Hippocampal Development in Ovine Fetuses with Growth Restriction?

Area of Science:

• Neuroscience
• Developmental Biology
• Pharmacology

Background:

• Early-onset fetal growth restriction (FGR) is linked to impaired fetal brain development, particularly in the hippocampus.
• Lactoferrin, known for anti-inflammatory and antioxidant properties, may offer neuroprotection.
• The effects of antenatal lactoferrin on FGR-induced brain alterations require further investigation.

Purpose of the Study:

• To determine if antenatal lactoferrin administration improves hippocampal structure in fetal sheep with FGR.
• To assess lactoferrin's impact on neuronal growth and neuroinflammation in the fetal hippocampus.
• To evaluate lactoferrin's influence on brain-derived neurotrophic factor (BDNF) levels and microglial activity.

Main Methods:

• Early-onset FGR was induced in ovine fetuses via single umbilical artery ligation.
• Lactoferrin was administered orally to ewes from 95 to 127 days gestational age (dGA).
• Hippocampal structure, neuronal morphology, BDNF levels, and microglial cell counts were analyzed at 127 dGA.

Main Results:

• Lactoferrin significantly increased neuronal abundance and altered neuronal morphology but did not change overall hippocampal structure.
• Hippocampal BDNF levels were elevated following lactoferrin exposure.
• Lactoferrin reduced microglial cell counts in the CA3 region, indicating region-specific anti-inflammatory effects.

Conclusions:

• Antenatal lactoferrin exhibits anti-inflammatory effects in the fetal brain and boosts BDNF levels.
• While beneficial for neurotrophic support and reducing inflammation, prolonged lactoferrin exposure may have complex effects on fetal brain development and hematological parameters.