Browsing by Author "Matjila, Mushi"

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    Open Access
    The differential expression of Kiss1, MMP9 and angiogenic regulators across the feto-maternal interface of healthy human pregnancies: implications for trophoblast invasion and vessel development
    (Public Library of Science, 2013) Matjila, Mushi; Millar, Robert; van der Spuy, Zephne; Katz, Arieh
    Genes involved in invasion of trophoblast cells and angiogenesis are crucial in determining pregnancy outcome. We therefore studied expression profiles of these genes in both fetal and maternal tissues to enhance our understanding of feto-maternal dialogue. We investigated the expression of genes involved in trophoblast invasion, namely Kiss1, Kiss1 Receptor (Kiss1R) and MMP9 as well as the expression of angiogenic ligands Vascular Endothelial Growth Factor-A ( VEGF-A) and Prokineticin-1 ( PROK1 ) and their respective receptors (VEGFR1, VEGFR2 and PROK1R ) across the feto-maternal interface of healthy human pregnancies. The placenta, placental bed and decidua parietalis were sampled at elective caesarean delivery. Real-time RT-PCR was used to investigate transcription, while immunohistochemistry and western blot analyses were utilized to study protein expression. We found that the expression of Kiss1 (p<0.001), Kiss1R (p<0.05) and MMP9 (p<0.01) were higher in the placenta compared to the placental bed and decidua parietalis. In contrast, the expression of VEGF-A was highest in the placental bed ( p<0.001 ). While VEGFR1 expression was highest in the placenta (p<0.01), the expression of VEGFR2 was highest in the placental bed (p<0.001). Lastly, both PROK1 (p<0.001) and its receptor PROK1R (p<0.001) had highest expression in the placenta. Genes associated with trophoblast invasion were highly expressed in the placenta which could suggest that the influence on invasion capacity may largely be exercised at the fetal level. Furthermore, our findings on angiogenic gene expression profiles suggest that angiogenesis may be regulated by two distinct pathways with the PROK1/PROK1R system specifically mediating angiogenesis in the fetus and VEGFA/VEGFR2 ligand-receptor pair predominantly mediating maternal angiogenesis.
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    The effect of COVID-19 on maternal newborn and child health (MNCH) services in Bangladesh, Nigeria and South Africa: call for a contextualised pandemic response in LMICs
    (2021-03-15) Ahmed, Tanvir; Rahman, Ahmed E; Amole, Taiwo G; Galadanci, Hadiza; Matjila, Mushi; Soma-Pillay, Priya; Gillespie, Bronwen M; El Arifeen, Shams; Anumba, Dilly O C
    Global response to COVID-19 pandemic has inadvertently undermined the achievement of existing public health priorities and laregely overlooked local context. Recent evidence suggests that this will cause additional maternal and childhood mortality and morbidity especially in low- and middle-income countries (LMICs). Here we have explored the contextual factors influencing maternal, neonatal and children health (MNCH) care in Bangladesh, Nigeria and South Africa amidst the pandemic. Our findings suggest that between March and May 2020, there was a reduction in utilisation of basic essential MNCH services such as antenatal care, family planning and immunization due to: a) the implementation of lockdown which triggered fear of contracting the COVID-19 and deterred people from accessing basic MNCH care, and b) a shift of focus towards pandemic, causing the detriment to other health services, and c) resource constraints. Taken together these issues have resulted in compromised provision of basic general healthcare. Given the likelihood of recurrent waves of the pandemic globally, COVID-19 mitigation plans therefore should be integrated with standard care provision to enhance system resilience to cope with all health needs. This commentary suggests a four-point contextualised mitigation plan to safeguard MNCH care during the pandemic using the observed countries as exemplars for LMIC health system adaptations to maintain the trajectory of progress regarding sustainable development goals (SDGs).
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    Kisspeptin regulation of genes involved in cell invasion and angiogenesis in first trimester human trophoblast cells
    (Public Library of Science, 2014) Francis, Víctor A; Abera, Aron B; Matjila, Mushi; Millar, Robert P; Katz, Arieh A
    The precise regulation of extravillous trophoblast invasion of the uterine wall is a key process in successful pregnancies. Kisspeptin (KP) has been shown to inhibit cancer cell metastasis and placental trophoblast cell migration. In this study primary cultures of first trimester human trophoblast cells have been utilized in order to study the regulation of invasion and angiogenesis-related genes by KP. Trophoblast cells were isolated from first trimester placenta and their identity was confirmed by immunostaining for cytokeratin-7. Real-time quantitative RT-PCR demonstrated that primary trophoblast cells express higher levels of GPR54 (KP receptor) and KP mRNA than the trophoblast cell line HTR8Svneo. Furthermore, trophoblast cells also expressed higher GPR54 and KP protein levels. Treating primary trophoblast cells with KP induced ERK1/2 phosphorylation, while co-treating the cells with a KP antagonist almost completely blocked the activation of ERK1/2 and demonstrated that KP through its cognate GPR54 receptor can activate ERK1/2 in trophoblast cells. KP reduced the migratory capability of trophoblast cells in a scratch-migration assay. Real-time quantitative RT-PCR demonstrated that KP treatment reduced the expression of matrix metalloproteinase 1, 2, 3, 7, 9, 10, 14 and VEGF-A, and increased the expression of tissue inhibitors of metalloproteinases 1 and 3. These results suggest that KP can inhibit first trimester trophoblast cells invasion via inhibition of cell migration and down regulation of the metalloproteinase system and VEGF-A.
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    Role of obesity and gestational diabetes mellitus status on the expression of kisspeptin, inflammatory markers and other endocrine signals, and their correlation with foetal outcomes and placental structure
    (2022) Musa, Ezekiel; Levitt, Naomi S; Matjila, Mushi
    Background: Maternal obesity and gestational diabetes mellitus (GDM) are associated with short and long-term health risks for the mother and child. The placenta produces hormones, including steroids and cytokines, that influence maternal glucose control. Current literature links kisspeptins with glucose-stimulated insulin secretion, and low plasma kisspeptin concentrations have been associated with GDM and markers of insulin resistance. In addition, maternal obesity is characterized by low-grade inflammation and insulin resistance. However, little is known about the effect of maternal obesity and GDM and their interaction on placental kisspeptin and inflammatory marker (TNFα, IL-6) expression, the relationship between placental and circulatory kisspeptin and inflammatory markers with placental villous morphology and maternal and neonatal parameters. There is also a paucity of data on the effect of maternal obesity and GDM on other endocrine signals (leptin, placental lactogen family members), growth factors (IGF2, VEGF), and steroidogenic hormone enzyme gene expression in the placenta. Aim: This work aimed to examine the effect of maternal obesity and/or GDM on molecular expression (placental, maternal and cord serum) of kisspeptin and inflammatory markers (TNFα, IL-6) and placental morphology, and how these effects relate to maternal and neonatal clinical parameters. Additionally, the work aimed to investigate the effect of maternal obesity and/or GDM on leptin, placental lactogen family members, growth factors, and steroidogenic hormone enzymes gene expression in the placenta. Methods: This study included 4 groups of South African pregnant women: Non-GDM, Non-obese (n=14); Non-GDM, Obese (n=19); GDM, Non-obese (n=15); GDM-Obese (n=23). At delivery, the women's placental tissue was fixed and processed for immunohistochemistry and histological assessment as well as snap-frozen for RT-qPCR and Western Blot analysis. Maternal and cord blood were also collected for the measurement of placenta-derived factors by ELISA. Data were compared by two-way ANOVA with Bonferroni multiple comparisons tests. Results: Maternal obesity and GDM had no effect on placental kisspeptin gene and protein expression, immunostaining or circulatory levels. There was a significant negative correlation between placental kisspeptin gene expression and volume of villous syncytiotrophoblasts and theoretical diffusion capacity in non-obese women irrespective of their GDM status. There was a significant inverse correlation between plasma kisspeptin protein and BMI and maternal systolic blood pressure in GDM women regardless of obesity. Cord serum kisspeptin concentration correlated negatively with BMI. Maternal obesity reduced placental Leptin and KISS1R gene expression in the absence of GDM. Overall, placental TNFα protein abundance by immunostaining was significantly higher in women with obesity irrespective of GDM status. TNFα staining of terminal villi syncytiotrophoblast was increased in women with obesity, while IL-6 staining of terminal villi stroma and foetal vessels was reduced in obese women, significantly so in GDM women. There was a positive correlation between the expression of placental TNFα gene and IL6 protein and maternal diastolic blood pressure in obese non-GDM and GDM women, respectively. In obese non-GDM women, maternal serum TNFα and IL-6 concentrations correlated negatively with placenta weight, foetoplacental ratio and volume of intervillous space, and theoretical and specific diffusion capacity, respectively. Women with obesity showed fewer terminal villi with fewer syncytiotrophoblast, foetal vessels and stroma dependent on GDM diagnosis while GDM influenced intervillous space volume by increasing it in obese groups. Maternal obesity also affected the surface areas for maternal-foetal exchange; the surface area of maternal blood space and foetal capillary were reduced in women with obesity regardless of GDM status. Again, the physiological diffusion gradients for oxygen transfer at the maternal-foetal interface were significantly reduced by maternal obesity. Conclusion: This study shows neither maternal obesity nor GDM influences kisspeptin levels, although maternal obesity in the absence of GDM seems to downregulate KISS1R, which may impact the kisspeptin-KISS1R signalling pathway. GDM rather than obesity may have a greater effect on TNF-α mediated maternal circulatory and placental inflammation. This study suggests that placental inflammation and insulin resistance may have a relationship with hypertension. In obese women alone, maternal inflammatory cytokines seem to be associated with altered placental structure and function. Indeed, maternal obesity was shown to compromise placental maturation and decrease the surface area and diffusion capacity required for maternal-foetal nutrient and oxygen exchange. These observations are likely to contribute novel insights into the interplay between metabolic dysfunction, obesity, and inflammation in the pathophysiology of GDM and placental dysfunction.
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    Stevens Johnson Syndrome and toxic epidermal necrolysis: maternal and foetal outcomes in twenty-two consecutive pregnant HIV infected women
    (Public Library of Science, 2015) Knight, Lauren; Todd, Gail; Muloiwa, Rudzani; Matjila, Mushi; Lehloenya, Rannakoe J
    Introduction Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) form a spectrum of a rare and life-threatening cutaneous drug reaction. SJS/TEN in pregnancy poses largely unknown risk factors and outcomes for both the mother and foetus compared to the general population. METHODS: We conducted a study of consecutive pregnant women admitted to single tertiary referral centre in South Africa with SJS/TEN over a 3 year period. They were all managed by the same medical team using the same protocols. We evaluated their underlying illnesses, offending drugs and the course of pregnancy and outcomes to determine factors influencing maternal and foetal outcomes. RESULTS: We identified twenty-two women who developed SJS/TEN while pregnant, all of them HIV-infected. Their median age was 29 years. The majority 16/22 (73%) had SJS, the milder variant of the disease affecting < 10% body surface area. Nevirapine was the offending drug in 21/22 (95%) cases. All 22 of the mothers survived with 3/22 (14%) developing postpartum sepsis. Pregnancy outcomes were known in 18/22 women and 9/18 (50%) babies were delivered by caesarean section. There were 2 foetal deaths at 21 and 31 weeks respectively and both were associated with post-partum sepsis. Postnatal complications occurred in 5 cases, 3 involving the respiratory system and the other two being low birth weight deliveries. Eight placentae and one foetus were sent for histology and none showed macroscopic or microscopic features of SJS/TEN. On follow-up, only 12/20 children were tested for HIV at 6 weeks post-delivery and none of them were HIV-infected. All had received prophylactic ARVs including nevirapine. CONCLUSIONS: TEN, the severe form of the disease, was associated with poorer foetal outcomes. SJS/TEN-associated mortality is not increased in HIV-infected pregnant women. Maternal SJS/TEN does not seem to commonly manifest in the foetus.