Downregulation of Placental Amino Acid Transporter Expression and mTORC1 Signaling Activity Contributes to Fetal Growth Retardation in Diabetic Rats

International Journal of Molecular Sciences
Jie XuHui Zhu

Abstract

Alterations in placental transport may contribute to abnormal fetal intrauterine growth in pregnancies complicated by diabetes, but it is not clear whether the placental amino acid transport system is altered in diabetic pregnancies. We therefore studied the changes in the expressions of placental amino acid transporters in a rat model of diabetes induced by streptozotocin, and tested the effects of hyperglycemia on trophoblast amino acid transporter in vitro. Our results showed that the expressions for key isoforms of system L amino acid transporters were significantly reduced in the placentas of streptozotocin-induced diabetic pregnant rats, which was associated with the decreased birthweight in the rats. A decreased placental efficiency and decreased placental mammalian target of rapamycin (mTOR) complex 1 (mTORC1) activity were also found in the rat model. In addition, hyperglycemia in vitro could inhibit amino acid transporter expression and mTORC1 activity in human trophoblast. Inhibition of mTORC1 activity led to reduced amino acid transporter expression in placental trophoblast. We concluded that reduced placental mTORC1 activity during pregnancy resulted in decreased placental amino acid transporter expression and, sub...Continue Reading

References

Oct 6, 2009·American Journal of Obstetrics and Gynecology·Juan A ArroyoHenry L Galan
Nov 17, 2011·World Journal of Diabetes·Anne Vambergue, Isabelle Fajardy
Apr 17, 2012·Cell·Mathieu Laplante, David M Sabatini
May 4, 2012·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Laura C KusinskiJocelyn D Glazier
Nov 15, 2012·The Journal of Clinical Endocrinology and Metabolism·Nina JanssonTheresa L Powell
Apr 20, 2014·Physiological Reports·Susanne LagerThomas Jansson
Apr 22, 2015·International Journal of Medical Sciences·Yoshio MatsudaShigeki Matsubara
Jun 19, 2015·International Journal of Molecular Sciences·Jie XuHui Zhu

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