The role of follistatin and granulocyte-colony stimulating factor in HIV-associated pre-eclampsia

Mdlalose, S.P.; Moodley, Jagidesa; Naicker, Thajasvarie

doi:10.1016/j.preghy.2019.12.012

Cited by 6 publications

(3 citation statements)

References 68 publications

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“…These findings suggest that Fst may play a crucial role in facilitating uterine receptivity ( 31 ). A decreased FST level was also observed in serum and placenta of women with preeclampsia (PE) ( 32 – 34 ), resulting in impaired trophoblast function through upregulating GDF11 levels in trophoblasts. The dysregulation of the FST-GDF11-Smad2/3 axis may be critical to trophoblast function, which adds more evidence to the essential role of FST on trophoblast during pregnancy ( 35 ).…”

Section: Introductionmentioning

confidence: 99%

Low follistatin level is a causal risk factor for spontaneous abortion: a two-sample mendelian randomization study

Gong,

Yang,

Liu

et al. 2024

Front. Endocrinol.

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BackgroundRecurrent pregnancy loss is a distressing event during pregnancy, and understanding its causal factors is crucial. Follistatin, a glycoprotein involved in folliculogenesis and embryogenesis, has been implicated as a potential contributor to the risk of spontaneous abortion. However, establishing a causal relationship requires rigorous investigation using robust methods.MethodsIn this study, we utilized mendelian randomization (MR), a powerful genetic epidemiological approach, to examine the causal relationship between follistatin levels and spontaneous abortion. We obtained instrumental variables strongly associated with follistatin levels from large-scale genome-wide association from the IEU database. The inverse variance weighting (IVW) method was taken as gold standard. We also performed sensitivity test to evaluate the robustness of our result.ResultsMR analysis revealed a significant causal relationship between low follistatin levels and spontaneous abortion (p = 0.03). Sensitivity analyses, including pleiotropy test, heterogeneity test, and leave-one-out analysis, all supported the robustness of our findings.ConclusionOur study provides compelling evidence supporting the causal relationship between low follistatin levels and increased risk of spontaneous abortion. These findings underscore the importance of follistatin in the etiology of spontaneous abortion and suggest potential preventive interventions. Modulating follistatin levels or relevant pathways could hold promise for reducing the incidence of spontaneous abortion and improving reproductive outcomes. The utilization of MRs strengthens the validity of our results by mitigating confounding and reverse causality biases. Further research is needed to elucidate the underlying molecular mechanisms and explore therapeutic strategies targeting follistatin levels.

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Section: Introductionmentioning

confidence: 99%

Low follistatin level is a causal risk factor for spontaneous abortion: a two-sample mendelian randomization study

Gong,

Yang,

Liu

et al. 2024

Front. Endocrinol.

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“…While Human Immunodeficiency Virus (HIV) infection, haemorrhage, and hypertensive disorders in pregnancy (HDP) are the main factors contributing to maternal mortality in South Africa [2]. Preeclampsia (PE) is a common and potentially fatal HDP, affecting 3-8% of all pregnancies worldwide [3]. It is diagnosed by a new onset high blood pressure of ≥140/90 mmHg with/without proteinuria (> 300 mg/d) and/or evidence of maternal organ dysfunction at or after 20 weeks of gestation [4].…”

Section: Introductionmentioning

confidence: 99%

Loss of regulation of complement C5 activation in HIV associated Preeclampsia

Govender¹,

Mduluza²,

Nandlal

et al. 2022

Preprint

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Objective: Maternal mortality remains a global health concern in developing countries that are also affected by HIV infection. Complement components are anaphylatoxin that mediate several growth factors necessary during pregnancy. An extensive stimulation of the complement system contributes to the pathogenesis of preeclampsia; hence its inhibition facilitates a successful pregnancy. The study evaluated the expression of complement components C2 and C5a in HIV and the association with preeclampsia. Materials and Methods: Serum samples were collected from 76 pregnant women of which 38 were preeclamptic and 38 normotensive pregnant. The participants were further stratified according to HIV infection status. Bio-Plex multiplex immunoassay method was used to quantify serum concentration of C5a and C2 complement components. Results: The C2 complement concentration was not significantly different between preeclamptic and normotensive pregnant women, irrespective of HIV status as well as pregnancy type. However, based on preeclamptic vs normotensive pregnancy type, the expression of C5a was significantly different ( p = 0.05). The C5a levels were downregulated in preeclampsia compared to normotensive women, irrespective of HIV status. Both C2 and C5a concentrations did not differ across all study groups. Conclusion: This novel study reports a loss of regulation of complement activation shown by the downregulation of C5a in preeclamptic compared to normotensive pregnant women, regardless of HIV status. Complement dysregulation affects the host innate defence, and as a consequence, intensifies placental and fetal injury. Moreover, HIV status did not influence the expression of both C5a and C2, irrespective of pregnancy type, this may be attributed to Highly Active Antiretroviral Therapy.

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“…Imbalance of two circulating factors associated with PE, follistatin and granulocyte-colony stimulating factor, could serve as a possible biomarker for PE in women with HIV. 32 The placenta plays a key role in vertical transmission from mother to fetus, and infections are important causes of morbidity and mortality, particularly for the fetus. Infections include Toxoplasma gondii, syphilis, Listeria monocytogenes, malaria, parvovirus B19, Zika virus, rubella virus, human cytomegalovirus (HCMV), and herpes simplex virus (HSV).…”

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confidence: 99%

Immune Regulation, Maternal Infection, Vaccination, and Pregnancy Outcome

PrabhuDas

Piper

Jean‐Philippe

et al. 2021

Journal of Women's Health

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About 12.5% of all maternal deaths in the United States are due to infectious causes. This proportion, although stable during the past three decades, represents an increase in infectious causes of mortality, as the overall mortality rate in U.S. pregnant women had increased steadily during that same period. During healthy pregnancies, a delicate immunological balance-in which a mother's immune system tolerates the semi-allogeneic fetus yet maintains immune competency against infectious agents-is achieved and maintained. This immunological paradigm, however, results in increased susceptibility to infectious diseases during pregnancy, particularly in later stages and during the early postpartum period. The inflammatory process induced by these infectious insults, as well as some noninfectious insults, occurring during pregnancy can disrupt this carefully achieved balance and, in turn, lead to a state of rampant inflammation, immune activation, and dysregulation with deleterious health outcomes for the mother and fetus. Elucidating mechanisms contributing to the disruption of this immunologic homeostasis, and its disruption by infectious pathogens, might offer opportunities for interventions to reduce maternal and fetal morbidity and mortality.

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The role of follistatin and granulocyte-colony stimulating factor in HIV-associated pre-eclampsia

Cited by 6 publications

References 68 publications

Low follistatin level is a causal risk factor for spontaneous abortion: a two-sample mendelian randomization study

Low follistatin level is a causal risk factor for spontaneous abortion: a two-sample mendelian randomization study

Loss of regulation of complement C5 activation in HIV associated Preeclampsia

Immune Regulation, Maternal Infection, Vaccination, and Pregnancy Outcome

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