Placental Insulin-Like Growth Factor-1 Receptor, Protein Kinase B and Mammalian Target of Rapamycin are Downregulated in HIV-1 Positive Women on Antiretroviral Drugs

Winifrida B. Kidima, Department of Zoology and Wildlife Conservation, College of Natural and Applied Sciences University of Dar es Salaam, PO Box 35064, Dar es Salaam, TanzaniaFollow
Gatambwa D. Mukandala, Department of Zoology and Wildlife Conservation, College of Natural and Applied Sciences University of Dar es Salaam, PO Box 35064, Dar es Salaam, TanzaniaFollow
Osiana Leonard, Department of Zoology and Wildlife Conservation, College of Natural and Applied Sciences University of Dar es Salaam, PO Box 35064, Dar es Salaam, TanzaniaFollow
Daniel Nkungu, Mwananyamala Referral Hospital, Departments of Obstetrics and Gynecology, PO Box 61665, Dar es Salaam, TanzaniaFollow

Section

Biological Sciences

Abstract

HIV-1 and ARV drugs uptake during pregnancy may change placental phenotype during pregnancy affecting fetal growth. We investigated the influence of maternal HIV-1 and ARV drugs on expression of placental genes important for fetus growth. A total 51 HIV-1 positives and 46 HIV-1 negative pregnant women were studied. Placental gene expression changes of insulin-like growth factor receptor 1 (IGF-1) R, mammalian target of rapamycin (mTOR), protein kinase B (AKT-1), sodium-coupled neutral amino acid transporters (Slc38a1, Slca38a2, Slc38a4), inhibin A, adrenomedullin and 11 beta-Hydroxysteroid dehydrogenase type (HSD)-2 were assessed by RT-qPCR. There was a significant decrease in mRNA expression of placental IGF-1R, mTOR, and AKT-1 in HIV-1 positive placentas compared to controls (p < 0.0001). There was also significant upregulation of an antiangiogenic molecule, inhibin A and downregulation of angiogenic molecule adrenomedullin in HIV-1 positive placenta (all p < 0.0001). However, the mRNA expression of placental Slc38a1 and Slca38a2 was higher in both HIV-1 positive and negative women delivering LBW babies compared to controls (p < 0.0001). The placental mRNA expression of 11 β-HSD-2 increased by 17 folds in HIV-1 negative and by 3.8 folds in HIV-1 positive women delivering LBW babies. IGF-1-P13-AKT-1-mTOR signaling pathway is dysregulated in placenta of HIV-1 positive women on ARV drugs. Higher mRNA expression levels of inhibin A and lower levels of adrenomedullin occur in placenta of HIV-1 positive women delivering LBW babies. ARV drugs and HIV-1 may be involved in the disruption of vascular tone of the placenta and therefore placental perfusion. Keywords: Pregnant women, HIV-1, ARV drugs, Placental IGF-1-AKT-1-mTOR signaling, inhibin A, adrenomedullin, amino acid transporters.

Recommended Citation

Kidima, Winifrida B.; Mukandala, Gatambwa D.; Leonard, Osiana; and Nkungu, Daniel (2021) "Placental Insulin-Like Growth Factor-1 Receptor, Protein Kinase B and Mammalian Target of Rapamycin are Downregulated in HIV-1 Positive Women on Antiretroviral Drugs," Tanzania Journal of Science: Vol. 47: Iss. 5, Article 15.
Available at:https://doi.org/10.4314/tjs.v47i5.16