The placenta‐brain‐axis

Abstract

All mammalian species depend on the placenta, a transient organ, for exchange of gases, nutrients, and waste between the mother and conceptus. Besides serving as a conduit for such exchanges, the placenta produces hormones and other factors that influence maternal physiology and fetal development. To meet all of these adaptations, the placenta has evolved to become the most structurally diverse organ within all mammalian taxa. However, commonalities exist as to how placental responses promote survival against in utero threats and can alter the trajectory of fetal development, in particular the brain. Increasing evidence suggests that reactions of the placenta to various in utero stressors may lead to long‐standing health outcomes, otherwise considered developmental origin of health and disease effects. Besides transferring nutrients and gases, the placenta produces neurotransmitters, including serotonin, dopamine, norepinephrine/epinephrine, that may circulate and influence brain development. Neurobehavioral disorders, such as autism spectrum disorders, likely trace their origins back to placental disturbances. This intimate relationship between the placenta and brain has led to coinage of the term, the placenta‐brain‐axis. This axis will be the focus herein, including how conceptus sex might influence it, and technologies employed to parse out the effects of placental‐specific transcript expression changes on later neurobehavioral disorders. Ultimately, the placenta might provide a historical record of in utero threats the fetus confronted and a roadmap to understand how placenta responses to such encounters impacts the placental‐brain‐axis. Improved early diagnostic and preventative approaches may thereby be designed to mitigate such placental disruptions.

Dynamics of Tryptophan Metabolic Pathways in Human Placenta and Placental-Derived Cells: Effect of Gestation Age and Trophoblast Differentiation

“…Recently, the importance of gut microbiome metabolism of TRP for gut–brain axis has been described ( Kaur et al, 2019 ; Gao et al, 2020 ). Similarly, placental metabolism of TRP might form a crucial component of the placenta–brain axis ( Rosenfeld, 2020a , b ). Considering the large spectrum of TRP metabolites and their roles in pregnancy, it is important to elucidate and understand the shifts in enzyme/transporter expression/activity occurring during gestation.…”

Evidence for the placenta-brain axis: multi-omic kernel aggregation predicts intellectual and social impairment in children born extremely preterm

“…The placenta is involved in hormone and neurotransmitter production and transfer of nutrients to the fetus, thus having direct influence on brain development. This intimate connection between the placenta and the brain is termed the placenta-brain axis [6,7]. Epidemiological and animal studies have linked genomic and epigenomic alterations in the placenta with neurodevelopmental disorders and normal neurobehavioral development [8][9][10].…”

“…For example, the Markers of Autism Risk in Babies: Learning Early Signs (MARBLES) study has identified a differentially methylated region containing a putative fetal brain enhancer in placentas from children diagnosed with ASD (N = 24) compared to placentas from typically developing (N = 23) children [11]. The study of molecular interactions within and between the transcriptome and epigenome that represent the placenta-brain axis may advance our understanding of fetal mechanisms involved in aberrant neurodevelopment [6].…”

Evidence for the Placenta-Brain Axis: Multi-Omic Kernel Aggregation Predicts Intellectual and Social Impairment in Children Born Extremely Preterm

“…The placenta is involved in hormone and neurotransmitter production and transfer of nutrients to the fetus, thus having direct influence on brain development. This connection between the placenta and the brain is termed the placenta-brain axis [6]. Epidemiological and animal studies have linked genomic and epigenomic alterations in the placenta with neurodevelopmental disorders and normal neurobehavioral development [7][8][9].…”

“…However, identifying genomic signatures of risk for neurodevelopmental disorders such as ASD in placenta is a challenging. Further study of molecular interactions representing the placenta-brain axis may advance our understanding of fetal mechanisms involved in aberrant neurodevelopment [6].…”