Human forkhead box protein 3 gene variants associated with altered susceptibility to idiopathic recurrent pregnancy loss: A retrospective case‐control study

Bahia, Wael; Zitouni, Hédia; Kanabekova, Perizat; Bauyrzhanova, Zhansaya; Shaimardanova, M.; Finan, Ramzi R.; Aimagambetova, Gulzhanat; Almawi, Wassim Y.

doi:10.1111/aji.13551

Cited by 5 publications

(5 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, this feature of FOXP3 may serve as a mechanism of maternal tolerance to semi-allograft embryos. This hypothesis proposing the role of Treg in RPL pathogenesis is supported by recent research findings, which suggest that FOXP3 gene variants and haplotypes could be associated with RPL [33,132].…”

Section: Immune Factorssupporting

confidence: 65%

See 1 more Smart Citation

Recurrent Pregnancy Loss Etiology, Risk Factors, Diagnosis, and Management. Fresh Look into a Full Box

Turesheva,

Aimagambetova,

Ukybassova

et al. 2023

JCM

Self Cite

View full text Add to dashboard Cite

Recurrent pregnancy loss is a complex health challenge with no universally accepted definition. Inconsistency in definitions involves not only the number of spontaneous abortions (two or three) that are accepted for recurrent pregnancy loss but the types of pregnancy and gestational age at miscarriage. Due to the heterogeneity of definitions and criteria applied by international guidelines for recurrent pregnancy loss, the true incidence of recurrent miscarriage, which is reported to range from 1% to 5%, is difficult to estimate. Moreover, the exact etiology of recurrent pregnancy loss remains questionable; thus, it is considered a polyetiological and multifactorial condition with many modifiable and non-modifiable factors involved. Even after thoroughly evaluating recurrent pregnancy loss etiology and risk factors, up to 75% of cases remain unexplained. This review aimed to summarize and critically analyze accumulated knowledge on the etiology, risk factors, relevant diagnostic options, and management approach to recurrent pregnancy loss. The relevance of various factors and their proposed roles in recurrent pregnancy loss pathogenesis remains a matter of discussion. The diagnostic approach and the management largely depend on the etiology and risk factors taken into consideration by a healthcare professional as a cause of recurrent miscarriage for a particular woman or couple. Underestimation of social and health consequences of recurrent pregnancy loss leads to compromised reproductive health and psychological well-being of women after miscarriage. Studies on etiology and risk factors for recurrent pregnancy loss, especially idiopathic, should be continued. The existing international guidelines require updates to assist clinical practice.

show abstract

Section: Immune Factorssupporting

confidence: 65%

“…Recently the role of forkhead 3 box protein (FOXP3) in RPL was proposed [ 33 , 131 , 132 ]. FOXP3 is a nuclear transcription factor required to induce immunosuppressive activity [ 131 , 133 ].…”

Section: Resultsmentioning

confidence: 99%

Recurrent Pregnancy Loss Etiology, Risk Factors, Diagnosis, and Management. Fresh Look into a Full Box

Turesheva,

Aimagambetova,

Ukybassova

et al. 2023

JCM

Self Cite

View full text Add to dashboard Cite

show abstract

“…Indeed, many researchers have reported that women with URPL have lower Tregs levels than normal patients ( 24 , 25 ). Up to now, numerous results generally suggest that lower Tregs level is associated with a higher risk of miscarriage in women with URPL ( 12 , 13 , 26 ). However, our study revealed for the first time that either lower or higher Tregs levels increase the risk of miscarriage in women with URPL.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of regulatory T cells in patients with unexplained recurrent pregnancy loss: friend or foe?

Liu,

Li,

Huang

et al. 2024

Front. Med.

View full text Add to dashboard Cite

BackgroundThis study aimed to investigate the role of regulatory T cells in patients with unexplained recurrent pregnancy loss (URPL).MethodsWe retrospectively analyzed 136 women who had experienced two or more miscarriages before 24 weeks of gestation for no obvious reason from May 2018 to October 2021. The basic clinical data of the patients and expression of lymphocyte subsets such as regulatory T cells (Tregs) and natural killer cells (NKs) by flow cytometry were collected to explore the risk factors of pregnancy outcome in URPL patients.ResultsA total of 136 URPL patients were enrolled in this study. Eventually, 50 patients attained clinical pregnancy. The median age was 31.8 ± 4.6 years in patients with clinical pregnancy. The univariate and multivariate logistic regression analyses indicated that Tregs was associated with the pregnancy outcomes of patients with URPL (odds ratio 0.63, 95% confidence interval 0.50–0.80). More importantly, a U-shaped association was found between Tregs and pregnancy outcome (p < 0.001), with either higher or lower Tregs levels adversely affecting pregnancy outcome.ConclusionTregs levels that are either too high or too low can harm pregnancy outcomes. It was expected to be a very promising quantitative biomarker for predicting pregnancy outcomes in URPL patients.

show abstract

“…Nevertheless, the precise pathophysiological mechanisms behind PCOS have yet to be fully elucidated. Genetic differences have been identified as a contributing factor to the pathophysiology of PCOS in many investigations [3,4]. Furthermore, it has been shown that there is a correlation between insulin resistance and the pathophysiology of PCOS [5,6].…”

Section: Introductionmentioning

confidence: 99%

Ghrelin Alleviates Inflammation, Insulin Resistance, and Reproductive Abnormalities in Mice with Polycystic Ovary Syndrome via the TLR4-NF-κB Signaling Pathway

Liu,

Wang,

Zhao

et al. 2024

Discovery Medicine

View full text Add to dashboard Cite

Background: Polycystic ovary syndrome (PCOS) commonly impacts fertile females with potentially severe effects on fertility and metabolism. Blood ghrelin levels are lower in PCOS patients, and exogenous supplements have been proposed for their potential to trigger anti-inflammatory effects at the cellular level. This study aimed to investigate whether pretreatment with ghrelin reduced inflammation, insulin resistance, and reproductive abnormalities in PCOS and the underlying mechanism of this disorder. Methods: Ghrelin supplementation was first tested in an inflammation model using human ovarian granulosa cells (KGN cells) that were built by treated with Lipolyaccharide. KGN cells were pretreated with ghrelin and exposed to lipopolysaccharide (LPS). Inflammatory gene expression and cytokine production were analyzed by Enzyme-linked immunosorbent assay (ELISA). Based on these results, the PCOS mice model was built with Dehydroepiandrosterone (DHEA) and a high-fat diet. The mRNA and protein expressions of inflammatory factors including Toll-like receptor 4 (TLR4), nuclear factor kappa-B-p65 (NF-κB-p65), Phospho-NF-κB-p65 (p-NF-κB-p65) and myeloid differentiation factor 88 (MYD88) related to the TLR4/NF-κB signaling pathway were evaluated in KGN cells and mouse ovarian tissues using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) and western blot, respectively. Lipid metabolism was quantified via an automated biochemical analyzer. Results: The mRNA and protein expressions of interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) in ghrelin pretreated KGN cells were lower than the LPS group (p < 0.05). Protein expression was reduced for TLR4, NF-κB-p65, and MYD88 within KGN cells of ghrelin groups compared to the LPS group (p < 0.05). Ghrelin treatment restored the estrous cycle and slowed weight gain and abdominal fat weight of PCOS mice (p < 0.05). Ghrelin treatment decreased the serum concentrations of testosterone, luteinizing hormone, insulin, IL-6, IL-1β, and TNF-α compared to the PCOS group (p < 0.05). Estradiol concentrations of mice treated with ghrelin were higher than the PCOS group (p < 0.05). The concentrations of low and high-density lipoprotein, triglyceride, and cholesterol in mice treated with ghrelin were lower than in the PCOS mice (p < 0.05). Inflammatory gene expression for IL-6, IL-1β, TNF-α, TLR4, NF-κB-p65, and MYD88 decreased in the ovarian tissues of ghrelin-treated mice compared to the PCOS group (p < 0.05), along with reduced protein expression of TLR4, p-NF-κB-p65, and MYD88 (p < 0.05). Conclusions: In the present study, ghrelin treatment effectively reduced inflammation in vitro, and attenuated insulin resistance and reproductive abnormalities in PCOS mice through the TLR4/NF-κB signaling pathway, highlighting potential therapeutic avenues for future PCOS treatments and research directions.

show abstract

Human forkhead box protein 3 gene variants associated with altered susceptibility to idiopathic recurrent pregnancy loss: A retrospective case‐control study

Cited by 5 publications

References 47 publications

Recurrent Pregnancy Loss Etiology, Risk Factors, Diagnosis, and Management. Fresh Look into a Full Box

Recurrent Pregnancy Loss Etiology, Risk Factors, Diagnosis, and Management. Fresh Look into a Full Box

Overexpression of regulatory T cells in patients with unexplained recurrent pregnancy loss: friend or foe?

Ghrelin Alleviates Inflammation, Insulin Resistance, and Reproductive Abnormalities in Mice with Polycystic Ovary Syndrome via the TLR4-NF-κB Signaling Pathway

Contact Info

Product

Resources

About