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BACKGROUND: Recurrent spontaneous abortion affects approximately 1–2% of reproductive-age women, with roughly half of RSA cases classified as unexplained recurrent spontaneous abortion (URSA). Genetic polymorphisms in eNOS gene have been shown to have significant implications across various disease processes. Nevertheless, the potential impact of eNOS gene polymorphisms on the susceptibility to URSA in Yunnan population has yet to be explored or documented. OBJECTIVE: This study aims to investigate the potential association between specific variations in the eNOS gene (VNTR 4b/a, - 786T > C, and + 894G > T) and the risk of URSA in Yunnan population. METHODS: A total of 243 URSA patients and 241 healthy females are involved in this study. We conducted amplification of the eNOS gene fragment and performed sanger sequencing to detect the specific eNOS gene polymorphisms, including VNTR 4b/a, - 786T > C, and + 894G > T. Using a multivariate logistic regression model, we evaluate the potential association between eNOS gene polymorphisms (VNTR 4b/a, - 786T > C, and + 894G > T) and the risk of URSA. Furthermore, serum NO levels were measured in URSA patients. RESULTS: The presence of VNTR 4a, - 786C, and + 894T alleles was found to be associated with an increased risk of URSA. Additionally, our study revealed a significant association between the G-C-4b haplotype of the investigated eNOS gene polymorphisms and a predisposition to URSA. Notably, these eNOS polymorphisms were shown to reduce serum NO levels in URSA patients. CONCLUSION: This study provides evidence supporting the association between eNOS gene polymorphisms, VNTR 4b/a, - 786T > C, and + 894G > T, and the occurrence of URSA in Yunnan Province, China. [ABSTRACT FROM AUTHOR]

Recurrent spontaneous abortion (RSA) is one of the most common complications during pregnancy and seriously affects women's physical and mental health. About 50% of RSA cases are of unknown etiology. Our previous study found that the decidual tissue of patients with unexplained recurrent spontaneous abortion (URSA) had low expression levels of serum and glucocorticoid-induced protein kinase (SGK) 1. Endometrial decidualization is a key link in the early stage of pregnancy and is crucial to the development and maintenance of pregnancy. Decidualization is the proliferation and differentiation of endometrial stromal cells into deciduals, which involves a complex physiological process such as ovarian steroid hormones (estrogen, progesterone, prolactin, etc.), growth factors, and intercellular signaling. The binding of estrogen and its receptor stimulates the synthesis of endometrial deciduating markers prolactin (PRL) and insulin-like growth factor binding protein 1 (IGFBP-1), which mediates the occurrence of decidualization. Among them, SGK1/ENaC is a signaling pathway closely related to decidualization. The purpose of this study was to further investigate the expression of SGK1 and decidualization-related molecules in the decidual tissue of URSA patients and to explore the potential mechanism of SGK1's protective effect in URSA patients and in mouse models. Decidual tissue samples from 30 URSA patients and 30 women who actively terminated pregnancy were collected, and a URSA mouse model was established and treated with dydrogesterone. Expression levels of SGK1 and its signaling pathway-related proteins (p-Nedd4-2, 14–3-3 protein and ENaC-a), estrogen and progesterone receptors (ERβ, PR), and decidualization markers (PRLR, IGFBP-1) were assessed. Our study found that SGK1, p-Nedd4-2, 14–3-3 proteins, and ENaC-a expression levels were reduced in the decidual tissue, the SGK1/ENaC signaling pathway was inhibited, and the expression levels of the decidualization markers PRLR and IGFBP-1 were downregulated in the URSA group compared with the controls. Additionally, the concentrations of E2, P, and PRL in the serum of mice were decreased in the URSA group compared with the controls. However, SGK1/ENaC pathway-related proteins, estrogen and progesterone and their receptors, and decidualization-related molecules were upregulated by dydrogesterone. These data suggest that estrogen and progesterone can induce decidualization by activating the SGK1/ENaC signaling pathway; disruption of this pathway can lead to the development of URSA. Dydrogesterone can increase the expression level of SGK1 protein in decidual tissue. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression and sources of high mobility group box 1 (HMGB1) protein in the maternal-fetal interface of patients with unexplained recurrent spontaneous abortion (URSA), and further to verify the role of HMGB1 in the etiology of URSA. Methods: 55 women at early pregnancy with URSA and 55 women undergoing selective termination of normal early pregnancy as control were included. The abortion tissues including villi and decidua were collected. The expression of HMGB1, CD45, CK7, and vimentin in abortion tissues was detected, and the localization and sources of HMGB1 were analyzed. Results: Infiltrating immune cells and expression of HMGB1 were significantly increased in villi and decidua in URSA group compared with those in the control group. In the URSA group, HMGB1 was colocalized with the CD45-labeled immune cells, and it was more obvious in decidua than in villi; in addition, HMGB1 was colocalized with the vimentin-labeled decidual stromal cells, but not with the CK7- labeled villous epithelial cells. Conclusion: High expression of HMGB1 in the maternal-fetal interface in URSA patients was actively secreted by the infiltrating immune cells, and decidual stromal cells may passively release HMGB1 during necrosis. [ABSTRACT FROM AUTHOR]

Background: Our previous study has identified an association of a single nucleotide polymorphism (SNP) in the miR-423 gene with recurrent spontaneous abortion (RSA). The presence of additional RSA-linked SNPs in the miR-423 gene remains unclear., Methods: We evaluated polymorphisms in the coding region of miR-423 in Han Chinese women with unexplained RSA (URSA)., Results: Significant differences were observed in the genotype and allele distribution of miR-423 rs8067576 between patients with RSA and control subjects. A robust association was found between an elevated RSA incidence and the presence of A/T heterozygosity in miR-423 rs8067576, with an odds ratio (OR) of 1.76 (95% confidence interval [CI]: 1.26 to 2.47, p = 0.000292). The rare allele T in the pre-miR-423 sequence was shown to cause a discernible structural change and a reduced ΔG value. Compared with the A allele, the rare T allele promoted cell proliferation. Furthermore, compared with the T allele, the A allele in the rs8067576 polymorphism exhibited a greater ability to inhibit the translation of proliferation-associated 2 group 4 (Pa2g4), which is the functional target of miR-423. The T allele in the rs8067576 polymorphism was also found to be more susceptible to the inhibition of cell proliferation induced by mifepristone., Conclusions: The rs8067576 A > T polymorphism in the miR-423 gene may serve as a genetic susceptibility locus for RSA. This polymorphism appears to contribute to an increased risk of acquiring URSA in humans by destroying mature miR-423., (© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Study design: Randomized trial. Objective: This study was designed to investigate the effects of different doses of estrogen on the expression of estrogen receptor (ER) in endometrial tissue and ovarian function in patients with unexplained recurrent spontaneous abortion (URSA). Methods: Eighty-eight patients with URSA in our outpatient department were randomly divided into three groups. They were treated with estradiol valerate (EV); standard dose of 4 mg/d (31 cases), high dose of 6 mg/d (27 cases) and 9 mg/d (30 cases). Progesterone was detected in the luteal phase, ovarian ovulation during follow-up treatment and the next month after drug withdrawal. ER expression in intima of EV 4 mg group, EV 6 mg group, and EV 9 mg group was detected by immunohistochemistry and PCR was performed before and 3 months after the treatment. Results: Anovulation of 88 URSA patients during hormone treatment was found as follows: 5 cases in the EV 4 mg group, 18 cases in the EV 6 mg group, 25 cases in the EV 9 mg group; Anovulation in the next month after drug withdrawal: 1 case in EV 4 mg group, 8 cases in EV 6 mg group, and 16 cases in EV 9 mg group. After stratified and grouped analysis, the expression of intimal ER in the EV 4 mg group, EV 6 mg, and EV 9 mg groups was significantly increased compared to before treatment in the 3 groups after treatment compared to before treatment (p <.05). There was no significant difference in ER expression between the three groups before and after treatment (p >.05). Conclusion: The higher the therapeutic dose of estrogen, the stronger the inhibition of ovarian ovulation, and the standard dose of estrogen has obvious advantages in increasing the expression of ER in intima. Limitation: 1) Insufficient sample size; 2) We need to increase the sampling time point to further observe the difference of estrogen in time effect, so as to obtain a more accurate action time of estrogen; 3) The longer-term effects of different doses of estrogen on intima were not studied, such as whether there are adverse pregnancy outcomes such as preterm birth, placental implantation, or premature exfoliation. [ABSTRACT FROM AUTHOR]

Unexplained recurrent spontaneous abortion (URSA) is believed to be associated with impaired immunosuppression at the maternal-fetal interface, but the detailed molecular mechanism remains unclear. The ATP-adenosine metabolic pathway regulated by CD39/CD73 has recently been recognized to be important in immunosuppression. This study aimed to investigate the regulation of decidual natural killer (dNK) cells and fetal extravillous trophoblast (EVT) cells by CD39 and CD73 in URSA, as well as the possible regulatory mechanism of CD39/CD73 via the TGF-β-mTOR-HIF-1α pathway using clinical samples and cell models. Fewer CD39+ and CD73+ cells were found in the URSA decidual and villous tissue, respectively. Inhibition of CD39 on dNK cells transformed the cells to an activated state with increased toxicity and decreased apoptosis, and changed their cytokine secretion, leading to impaired invasion and proliferation of the co-cultured HTR8/SVneo cells. Similarly, inhibition of CD73 on HTR8/SVneo cells decreased the adenosine concentration in the cell culture media, increased the proportion of CD107a+ dNK cells, and decreased the invasion and proliferation capabilities of the HTR8/SVneo cells. In addition, transforming growth factor-β (TGF-β) triggered phosphorylation of mammalian target of rapamycin (mTOR) and Smad2/Smad3, which subsequently activated hypoxia-inducible factor-1α (HIF-1α) to induce the CD73 expression on the HTR8/SVneo cells. In summary, reduced numbers of CD39+ and CD73+ cells at the maternal-fetal interface, which may be due to downregulated TGF-β-mTOR-HIF-1α pathway, results in reduced ATP-adenosine metabolism and increased dNK cytotoxicity, and potentially contributes to URSA occurrences.

Unexplained recurrent spontaneous abortion (URSA) is believed to be associated with impaired immunosuppression at the maternal-fetal interface, but the detailed molecular mechanism remains unclear. The ATP-adenosine metabolic pathway regulated by CD39/CD73 has recently been recognized to be important in immunosuppression. This study aimed to investigate the regulation of decidual natural killer (dNK) cells and fetal extravillous trophoblast (EVT) cells by CD39 and CD73 in URSA, as well as the possible regulatory mechanism of CD39/CD73 via the TGF-β-mTOR-HIF-1α pathway using clinical samples and cell models. Fewer CD39+ and CD73+ cells were found in the URSA decidual and villous tissue, respectively. Inhibition of CD39 on dNK cells transformed the cells to an activated state with increased toxicity and decreased apoptosis, and changed their cytokine secretion, leading to impaired invasion and proliferation of the co-cultured HTR8/SVneo cells. Similarly, inhibition of CD73 on HTR8/SVneo cells decreased the adenosine concentration in the cell culture media, increased the proportion of CD107a+ dNK cells, and decreased the invasion and proliferation capabilities of the HTR8/SVneo cells. In addition, transforming growth factor-β (TGF-β) triggered phosphorylation of mammalian target of rapamycin (mTOR) and Smad2/Smad3, which subsequently activated hypoxia-inducible factor-1α (HIF-1α) to induce the CD73 expression on the HTR8/SVneo cells. In summary, reduced numbers of CD39+ and CD73+ cells at the maternal-fetal interface, which may be due to downregulated TGF-β-mTOR-HIF-1α pathway, results in reduced ATP-adenosine metabolism and increased dNK cytotoxicity, and potentially contributes to URSA occurrences. [ABSTRACT FROM AUTHOR]

The occurrence of unexplained recurrent spontaneous abortion (URSA) is closely related to immune system disorders, however, the underlying mechanisms remain unclear. The purpose of this study was to investigate the expression of GRIM-19 in URSA and the possible pathogenesis of URSA according to macrophage polarization. Here, we showed that GRIM-19 was downregulated in the uterine decidual macrophages of patients with URSA and that GRIM-19 downregulation was accompanied by increased M1 macrophage polarization. Furthermore, the expression levels of glycolytic enzymes were substantially enhanced in the uterine decidual macrophages of URSA patients, and glycolysis in THP-1-derived macrophages was further enhanced by the downregulation of GRIM-19. Additionally, the increase of M1 macrophages resulting from the loss of GRIM-19 was significantly reversed in cells treated with 2-deoxy-D-glucose (2-DG, an inhibitor of glycolysis). To provide more direct evidence, GRIM-19 deficiency was shown to promote macrophage polarization to the M1 phenotype in GRIM-19+/- mouse uteri. Overall, our study provides evidence that GRIM-19 deficiency may play a role in regulating macrophage polarization in URSA, and that glycolysis may participate in this process., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In this study, we aimed to investigate the expression of OX40, OX40L, PD-1 and PD-L1 in patients with unexplained recurrent spontaneous abortion (URSA) compared to normal pregnancies (NP). A total of 50 patients who were diagnosed with URSA and 41 NP were recruited to this study. Real-time polymerase chain reaction (RT-PCR) was used to determine the expression of OX40, OX40L, PD-1 and PD-L1 in decidual tissues; Immunohistochemistry (IHC) was conducted to characterize the distribution of the involved genes in decidual tissues; Double immunofluorescence staining was used to prove the localization of the involved genes in decidual tissues. The concentrations of OX40L and PD-L1 in plasma were measured with enzyme-linked immunosorbent assay (ELISA). The expression of OX40L in the decidua of URSA patients was significantly increased compared to that in the NP group, while the expression of PD-L1 in the URSA group was decreased compared to that in the NP group. Both proteins are localized in the decidual stroma as analyzed by double immunofluorescence staining. The staining results were confirmed at the mRNA level of decidual tissues, while the mRNA level of peripheral blood showed no significant difference. In conclusion, the results suggest that decidual stromal cells may promote the interaction with OX40 on T cells by upregulating the expression of OX40L and reduce the interaction with PD-1 on T cells by downregulating the expression of PD-L1 in URSA patients, which may interfere with the immune tolerance of the maternal-fetal interface, leading to poor pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Deployment of small cells over the existing cellular network is an effective solution to improve the system coverage and throughput of fifth generation (5G) mobile communication networks. The arrival of the 5G mobile networks have demonstrated the importance of advanced scheduling techniques to manage the limited frequency spectrum available while achieving 5G transmission requirements. Cellular networks of the future necessitate the formulation of efficient resource allocation schemes that mitigate the interference between the different cells. In this research work, we formulate an optimization problem for heterogenous networks (HetNets) for resource allocation to maximize the system throughput among the cell center users (CCUs) and cell edge users (CEUs). We solve the optimization problem by effective utilization of the weight factors distribution for resource allocation. A novel Utility-based Resource Scheduling Algorithm (URSA) optimizes the resource sharing among the users with better delay budget of each application. The designed URSA ameliorates fairness along with reduced cross layer interference for real and non-real time applications. Performance of the URSA has been evaluated and compared most relevant state of art algorithms using the matlab based simulators. Furthermore, simulation results validate the superiority of the proposed scheduling scheme against conventional techniques in terms of throughput, fairness, and spectral efficiency. [ABSTRACT FROM AUTHOR]

The pigment and structural color of insects play crucial roles in body protection, ecological adaptation, and signal communication. Epidermal melanization is a common and main coloring pattern, which results in broad phenotypic diversity. Melanin is one of the compounds contributing to dark brown-black pigmentation, which is synthesized from dopamine and tyrosine by the melanin metabolism pathway. The Ursa mutant of the silkworm Bombyx mori is a body-color mutant characterized by excessive melanin pigmentation in the larval epidermis. However, the exact gene responsible for this phenotype remains unclear. Here, we performed positional cloning of the gene responsible for Ursa , which was mapped to an 83-kb region on chromosome 14. The genomic region contains a protein-coding gene encoding a transcription factor, which was designated BmSoxD. The mutation site was determined by analysis of nucleotide sequences of the genomic region corresponding to BmSoxD , which identified a 449-bp transposable sequence similar to that of the B. mori transposon Helitron inserted into the sixth intron. BmSoxD was dramatically overexpressed in the epidermis of Ursa at the end of the molting stage compared with that of wild-type B. mori. Overexpression of BmSoxD led to upregulation of genes involved in the melanin metabolism pathway, whereas knocking down BmSoxD via small interfering RNAs blocked melanin pigment production in the larval epidermis. These data indicate that the mutation in BmSoxD is responsible for the Ursa mutant phenotype. We propose that the transposable sequence insertion causes abnormal overexpression of BmSoxD at the molting stage in the Ursa mutant, resulting in excessive melanin synthesis and its accumulation in epidermal cells. [Display omitted] • BmSoxD is the candidate gene of the Ursa mutant. • BmSoxD is dramatically overexpressed in the Ursa epidermis. • BmSoxD regulates melanin synthesis in the epidermis. [ABSTRACT FROM AUTHOR]