Paternal knockout of Slc38a4 /SNAT4 causes placental hypoplasia associated with intrauterine growth restriction in mice

Significance Although it has been suggested that system A amino acid transporters are involved in mammalian placental or embryonic development, most studies in this field have relied on in vitro experiments using primary cells/cytoplasts from human placentas. The present study provides genetic evidence of the developmental roles of system A amino acid transporters and identifiesSlc38a4 /SNAT4 as being critical to embryonic and placental development in mice. In addition, a blood metabolome analysis provides unequivocal evidence thatSlc38a4 /SNAT4 plays a key role in the supply of amino acids to the fetus. These results provide insights into the link between genetic alterations and the nutritional environment of the fetus, which may affect its development to term.