Fig. 10: Proposed model linking elevated DEPTOR expression to impaired trophoblast mTOR signaling and reduced amino acid transport in human fetal growth restriction. | Cell Death Discovery

Fig. 10: Proposed model linking elevated DEPTOR expression to impaired trophoblast mTOR signaling and reduced amino acid transport in human fetal growth restriction.

From: Normalization of trophoblast mTOR signaling rescues impaired function in primary human trophoblast cells isolated from pregnancies complicated by fetal growth restriction

Fig. 10: Proposed model linking elevated DEPTOR expression to impaired trophoblast mTOR signaling and reduced amino acid transport in human fetal growth restriction.

The findings of the present study support a model in which trophoblast DEPTOR expression is upregulated in human FGR, leading to inhibition of both mTORC1 and mTORC2 signaling pathways. Inhibition of mTORC1 increases the ubiquitination of specific System A (SNAT2) and L (LAT1) amino acid transporter isoforms via activation of Nedd4-2, resulting in decreased transporter abundance at the syncytiotrophoblast plasma membrane and reduced placental System A and L amino acid transport activity. Simultaneously, the inhibition of mTORC2 decreases Cdc42 expression, disrupting actin cytoskeletal dynamics required for amino acid transporter trafficking, further limiting fetal amino acid availability. Hypoxia, a hallmark of FGR, contributes to elevated DEPTOR expression in trophoblast cells, linking environmental stress to mTOR suppression. These molecular events converge to impair amino acid uptake from maternal circulation and restrict nutrient delivery to the fetus, contributing to reduced fetal growth. Red arrows indicate upregulation; blue arrows indicate downregulation; red dashed lines represent hypoxia-induced effects; red text highlights key outcomes in FGR trophoblast cells.

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