Journey to the Center of the Fetal Brain: Environmental Exposures and Autophagy

Abstract

Fetal brain development is known to be affected by adverse environmental exposures during pregnancy, including infection, inflammation, hypoxia, alcohol, starvation, and toxins. These exposures are thought to alter autophagy activity in the fetal brain, leading to adverse perinatal outcomes, such as cognitive and sensorimotor deficits. This review introduces the physiologic autophagy pathways in the fetal brain. Next, methods to detect and monitor fetal brain autophagy activity are outlined. An additional discussion explores possible mechanisms by which environmental exposures during pregnancy alter fetal brain autophagy activity. In the final section, a correlation of fetal autophagy activity with the observed postnatal phenotype is attempted. Our main purpose is to provide the current understanding or a lack thereof mechanisms on autophagy, underlying the fetal brain injury exposed to environmental insults.

Maternal folic acid impacts DNA methylation profile in male rat offspring implicated in neurodevelopment and learning/memory abilities

“…These three transcription factors coordinate with their downstream target genes to promote self-renewal and pluripotency of stem cells, thereby impacting embryonic development and neurodevelopment. Autophagy, a self-degradative process that acts as a pro-survival or pro-death mechanism depending on different physiological or pathological conditions [ 20 ], is important for embryonic development, neural proliferation, and differentiation during brain development [ 21 , 22 ]. Tight junctions are essential for establishing the selectively permeable barrier between neighboring cells, tight junctions formed between brain capillary endothelial cells help to create a blood-brain barrier that acts to protect the brain from harmful substances and maintain brain homeostasis, and modified tight junction protein expression and disrupted blood-brain barrier structure are observed in cerebral pathologies [ 23 , 24 ].…”

Metabolic adaptations to hypoxia in the neonatal mouse forebrain can occur independently of the transporters SLC7A5 and SLC3A2

“…Another potentially linked mechanism may be through alterations in autophagy, which is thought to be important for the maintenance of ATP production under conditions of hypoxia 35 . Autophagy is an important process in the developing brain and is strictly controlled, but may be influenced by environmental exposures 43 . Although autophagy in response to cellular stress may represent an adaptive mechanism which helps to maintain cellular homeostasis, its role in hypoxia–ischaemia is controversial 43 , with some studies suggesting that it may contribute to neuronal injury while 2 , 44 others propose a protective role.…”

“…Autophagy is an important process in the developing brain and is strictly controlled, but may be influenced by environmental exposures 43 . Although autophagy in response to cellular stress may represent an adaptive mechanism which helps to maintain cellular homeostasis, its role in hypoxia–ischaemia is controversial 43 , with some studies suggesting that it may contribute to neuronal injury while 2 , 44 others propose a protective role. Also of note is the role of SLC7A5 in transporting thyroid hormone across the plasma membrane 45 , 46 .…”

Maternal Folic Acid Impacts DNA Methylation Profile in Male Rat Offspring Associated With Neurodevelopment and Learning/Memory Abilities

“…These three transcription factors coordinate with their downstream target genes promotes self-renewal and pluripotency of stem cells, thereby impacting embryonic development and neurodevelopment. Autophagy, a self-degradative process that acts as a pro-survival or pro-death mechanism depending on different physiological or pathological conditions [19], is important for embryonic development, neural proliferation and differentiation during brain development [20,21]. Tight junctions are essential for establishing the selectively permeable barrier between neighboring cells, tight junctions formed between brain capillary endothelial cells help creating blood-brain barrier that act to protect the brain from harmful substances and maintain brain homeostasis, modi ed tight junction protein expression and disrupted blood-brain barrier structure are observed in cerebral pathologies [22,23].…”