VOLUME 69 : 2021

Placental immunolocalization of mTOR and downstream signaling targets in Filipino women with gestational diabetes mellitus

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Maria Ruth B. Pineda Cortel, Hazel Mae A. Piala, Brian Akhaphong, Therriz P. Mamerto,  Sharisse T. Diaz, Jemima G. Martinez, Jaynielle S. Quiaoit, Gersa May S. Rosales, Zianella V. Zamora, Rowen T. Yolo, Emilyn U. Alejandro Macalintal, Carinna Andrea Reyes, & Luis Maria B. Garcia

ARTICLE DOI: https://doi.org/10.53603/actamanil.67.2019.rkxa5859

The function of mechanistic target of rapamycin (mTOR) during pregnancy involves cellular nutrient transport in placenta from maternal to fetal environment. In pregnancies complicated by gestational diabetes mellitus (GDM), dysregulation of mTOR and its downstream targets were observed that can cause alteration in placental nutrient transport leading to abnormalities in fetal growth and development. This study aimed to determine the protein expression of mTOR, phosphorylation status p-mTOR and its downstream targets: p-4EBPI and p-S6 in syncytiotrophoblast and stromal cells between GDM and non-GDM placenta. Immunohistochemistry was performed with antibodies against mTOR, p-mTOR, p-4EBPI and p-S6 in 20 GDM and 36 non-GDM human term placenta. Results showed an increase in the net placental weight and fetal weight from GDM group compared to non-GDM group. This was associated with strong chromogen intensities of mTOR, p-mTOR, p-S6 in syncytiotrophoblast of GDM placenta and strong chromogen intensities of mTOR, p-mTOR, p-S6 and p-4EBP1 in stromal cells of GDM placenta. Expression levels of p-mTOR, p-4EBP1, and p-S6 in syncytiotrophoblast and stromal cells in GDM placenta were found to be positively correlated with fetal weight. Together, we conclude that the stronger expression of mTOR and its downstream targets in the placenta collected from GDM women suggest its involvement in the pathophysiology of GDM. Further studies to assess the effect of GDM on nutrient transport via mTOR pathway is warranted. Also, functional analysis focusing on molecular mechanisms and metabolomics related with GDM development may be performed.


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