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    The role of trophoblast cell receptor expression in HIV-1 passage across the placenta in pre-eclampsia: an observational study
    (Wiley, 2016-10-03) Dorsamy, V.; Vallen, C.; Haffejee, Firoza; Moodley, J.; Naicker, T.
    Objective To compare expression of markers of HIV and associated receptors (p24, CD4, CCR5 and ICAM-2) in placentae and umbilical cords of HIV-associated and pre-eclamptic pregnancies to elucidate any association between these conditions in mother-to-child transmission. Design Cross-sectional immunohistochemical analysis of target receptor expression. Setting Laboratory-based study of primigravidae attending a district hospital in South Africa. Population or sample Retrospectively collected placental tissue (stratified into four groups according to HIV status of normotensive and pre-eclamptic participants (n = 20/group). Method Immunohistochemistry utilising CD4 (1:1), p24 (1:10), CCR5 (1:80) and ICAM-2 (1:100) antibodies was performed using light microscopy for image acquisition and analysis. Main outcome measures Evaluate the expression of receptors on syncytiotrophoblast involved in in utero transmission of HIV. Results Syncytiotrophoblast was immunopositive for CD4 and CCR5 antibody with greater expression of CCR5 in HIV-positive versus HIV-negative groups (F1,159 = 6.979, P = 0.009) and normotensive versus pre-eclamptic groups (F1,159 = 8.803, P = 0.003). p24 was present in both placentae and umbilical cords of babies that were HIV-negative at 6 weeks. ICAM-2 immunostaining was observed in the syncytiotrophoblast across study groups and was significantly higher in the HIV-negative pre-eclamptic group (v2 (3) = 45.3; P < 0.001). Conclusion Concurrent CD4 and CCR5 receptor expression demonstrates possible in utero viral entry routes across the placental barrier. ICAM-2 expression may influence HIV passage across the placenta or restoration of risk of pre-eclampsia in HAART-treated mothers. HIV was found in fetal circulation regardless of antiretroviral treatment. Further confirmatory ultrastructural and molecular work is warranted.
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    Placental leptin mRNA expression and serum leptin levels in pre-eclampsia associated with HIV infection
    (Taylor and Fancis Online, 2016-10-03) Haffejee, Firoza; Naicker, Thajasvarie; Singh, Moganavelli; Kharsany, Ayesha B.M.; Adhikari, Miriam; Singh, Ravesh; Maharaj, Niren; Moodley, Jagidesa
    Leptin, primarily produced by adipocytes, is implicated in the development of pre-eclampsia. This study examines placental leptin production and serum leptin levels in HIV infected and uninfected normoten-sive and pre-eclamptic pregnancies. Placental leptin production was analysed by RT-PCR and serum lep-tin levels by ELISA in normotensive (n ¼ 90) and pre-eclamptic (n ¼ 90) pregnancies which were further stratified by HIV status. Placental leptin production was higher in pre-eclampsia compared to normoten-sive pregnancies irrespective of HIV status (p ¼ .04). Serum leptin was non-significantly raised in HIV uninfected (p ¼ .42) but lower in HIV-infected (p ¼ .03) pre-eclampsia. The latter had lower BMI (p ¼ .007) and triceps skin-fold thickness (p < .001) than the HIV uninfected groups with a significant correlation between serum leptin and triceps skin-fold thickness (p < .001), indicative of less adipose tissue in HIV-infected women with consequently lower serum leptin. Thus, serum leptin levels are not indicative of increased placental production when pre-eclampsia is associated with HIV infection.
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    Endoglin in HIV-associated preeclamptic placentae
    (Informa Healthcare, 2015) Govender, Nalini; Naicker, Thajasvarie; Moodley, Jagidesa
    Objective: To examine the placental immunoexpression of endoglin (Eng), in HIV-negative and HIV-positive normotensive (N and N+) and preeclamptic (P and P+) pregnancies at term, using immunohistochemistry and immunoelectron microscopy. Results: Strong Eng immunoreactivity was observed within endothelial cells, syncytio-and cyto-trophoblast cell populations. All extravillous trophoblast cells were immuno-positive for Eng. Subcellularly, gold particles were immunolocalised within the endoplasmic reticulum, and mitochondria. Immunoexpression of Eng differed signifi-cantly between exchange (p = 0.02) and conducting villi (p50.001). A higher Eng immunoexpression was observed in both villi types of the preeclamptic compared to normotensive groups. Irrespective of pregnancy type (normotensive versus PE), there was no significant effect of HIV status on Eng immunoexpression within the exchange and conducting villi. Conclusion: The immunostaining of Eng within the endothelial cells, syncytio-, cyto- and extravillous trophoblast cell populations of HIV-associated preeclamptic placentae is novel. Endoglin and its soluble component remains an area for dynamic placental exploration in preeclampsia development.