American Journal of Reproductive Immunology最新文献

Background

Maternal immune tolerance to the semi-allogeneic fetus is essential for successful pregnancy, while immune defense against pathogens must be preserved. Decidual macrophages (DMs) are critical regulators at the maternal–fetal interface, involved in trophoblast invasion, vascular remodeling, and immune modulation.

Methods

This review integrates findings from human studies, animal models, and in vitro experiments to explore how arginine metabolism regulates macrophage polarization and pregnancy outcomes.

Results

Arginine metabolism influences DM function via two major pathways: iNOS promotes M1 polarization and pro-inflammatory activity, while Arg-1 supports M2 polarization, tissue remodeling, and immune tolerance. Dysregulation of this balance is associated with pregnancy complications such as pre-eclampsia and fetal growth restriction. Pathogens like Helicobacter pylori and Mycobacterium tuberculosis exploit Arg-1 activity to evade host immunity. Clinical studies also suggest that L-arginine supplementation can improve placental function and fetal growth.

Conclusion

Arginine metabolism is a key modulator of macrophage polarization and immune balance in pregnancy. Targeting this pathway may offer novel therapeutic strategies to improve maternal and fetal outcomes.

Background

The relationship between the immune system and embryo implantation is intricate and not yet fully understood. Although a genetically normal (euploid) embryo is essential, successful implantation also relies on carefully regulated immune responses that promote tolerance and prevent rejection. The main objective of this study was to examine the paternal levels of the immunoregulatory factors HLA-G, transforming growth factor (TGF)-ß and interleukin (IL)-6 and to investigate possible correlations with other semen parameters, age and pregnancy outcome of the female partner.

Methods

Seminal plasma samples from 225 men were collected from 2022 to 2025, divided into four groups (live birth, biochemical pregnancy, abortion, no pregnancy) and determined for immunological profiling using commercial HLA-G, TGF-ß and IL-6 enzyme-linked immunosorbent assay (ELISA) kits.

Results

SHLA-G levels were significantly lower in the live birth group compared to biochemical pregnancies (p < 0.001) non-pregnancies (p < 0.001) and in abortions compared to non-pregnancies (p = 0.004). TGF-β levels were reduced in all pregnancy-related groups versus non-pregnancies (p < 0.001). IL-6 levels were lower in biochemical pregnancies compared to non-pregnancies (p = 0.017). Absolute HLA-G levels were lower in live births (p < 0.001) and were reduced in abortions (p = 0.004) compared to non-pregnancies. Absolute TGF-ß values were significantly lower in the live birth group (p < 0.001) compared to non-pregnancies. Absolute TGF-β and IL-6 levels were also decreased in biochemical pregnancies compared to non-pregnancies (p < 0.001 and p = 0.03, respectively).

Conclusion

Our findings show that seminal plasma levels of HLA-G, TGF-β and IL-6 differ significantly among pregnancy outcome groups in ART cycles, underlining a potential role of these immunological factors in influencing reproductive success. These results highlight the importance of seminal immunological profiling as a possible predictive tool for ART outcomes and warrant further investigation in larger cohorts.

Problem

This study aimed to evaluate the relationship between first-trimester white blood cell (WBC) levels and adverse obstetric and neonatal outcomes, and to identify a WBC threshold linked to poor prognosis.

Method of Study

We conducted a retrospective cohort study of healthy singleton pregnancies delivered between 2014 and 2023. Women with fever at the time of the first-trimester test, infection, or autoimmune diseases were excluded. Participants were categorized into eight groups based on WBC count (7500 to ≥15 000/µL). A high WBC group (≥14 000/µL, n = 258) was compared with a randomly selected control group (n = 516; WBC 7500–9999). Maternal and laboratory data were obtained from medical records. Outcomes included obstetric, perinatal, and neonatal complications. Statistical analyses used Chi-square, analysis of variance (ANOVA), and multivariate logistic regression to estimate adjusted odds ratios (aORs).

Results

Among 3895 pregnancies, higher first-trimester WBC counts were associated with increased pre-pregnancy BMI, nulliparity, and in vitro fertilization conception. Groups with elevated WBC counts showed significantly higher risks of preeclampsia, gestational diabetes (GDM), and preterm birth (PTB) before 34 and 36 weeks. Neonatal outcomes, including lower birth weight, higher rates of gestational age (SGA) and neonatal intensive unit (NICU) admission, were also more frequent in higher WBC groups. In a nested case–control analysis, WBC ≥14 000 was independently associated with increased risks of preeclampsia (aOR 3.54), PTB before 34 weeks (aOR 5.65) and 36 weeks (aOR 6.96), SGA (aOR 6.41), and NICU admission (aOR 2.11).

Conclusion

High first-trimester WBC counts (≥14 000/µL) are significantly associated with PTB, preeclampsia, SGA, and NICU admission and may serve as an early clinical predictor.

Problem

This study aimed to investigate whether Lacticaseibacillus rhamnosus GG intake during pregnancy influences maternal cytokine levels and lymphocyte subpopulations.

Method

Pregnant women were categorized into three groups: those with a history of spontaneous preterm delivery (PTD) (n = 40), those with a history of preeclampsia (n = 40), and nulliparous or parous women without a history of PTD or preeclampsia (n = 40). Participants were randomized to receive either L. rhamnosus GG or a placebo. Maternal blood samples were collected at baseline before gestational week 19 (visit 1) and around gestational weeks 25 and 35 (visits 2 and 3).

The primary outcome was the change in tumor necrosis factor-alpha (TNF-α) levels in monocytes after stimulation of maternal blood with Escherichia coli lipopolysaccharide (LPS). Secondary outcomes included lymphocyte subpopulation analysis and changes in TNF-α, interleukin (IL)-10, and IL-12 levels after stimulation with E. coli LPS, Lactobacillus paracasei, or Pseudomonas aeruginosa.

Results

In the intention-to-treat analysis, no significant differences in TNF-α levels were observed. However, a sensitivity analysis excluding participants with fever or recent antibiotic use (n = 27) revealed a significant decrease in TNF-α levels in the intervention group at visit 2 compared to an increase in the placebo group (mean difference −11785 cells/mL, 95% CI: −22459 to −1287, p = 0.03). Secondary analyses showed lower total lymphocyte, T-cell, IL-10, and IL-12 levels at visit 2 and higher IL-10 and IL-12 levels at visit 3 in the intervention group.

Conclusions

Although L. rhamnosus GG did not significantly affect TNF-α levels, its influence on lymphocyte and cytokine levels warrants further investigation through larger trials.

Objective

We aimed to examine the expression levels of thrombomodulin (THBD) and C-X-C motif ligand 6 (CXCL6/GCP-2) in the serum and placental tissues of pregnant women with preeclampsia (PE) and assess their clinical significance.

Methods

In this cross-sectional study, a cohort comprising 96 pregnant women diagnosed with preeclampsia (PE) and 119 healthy pregnant counterparts was selected from Jiangxi Maternal and Child Health Hospital, encompassing January 2024 to December 2024. The levels of THBD and CXCL6 in serum and placental tissues were assessed. The Mann‒Whitney U test was used to compare the differences between two groups, and the Spearman test was used to evaluate the risk factors for PE via correlation analysis.

Results

Serum THBD and CXCL6 levels were significantly elevated in the PE group compared to controls (p < 0.001), with a positive correlation between the two markers (r = 0.41, p < 0.001). Immunohistochemical analysis demonstrated reduced THBD and CXCL6 expression in placental syncytiotrophoblasts (p < 0.05), alongside diminished THBD immunoreactivity in vascular endothelial cells (p < 0.05). Multivariate logistic regression identified CXCL6, uric acid (UA), and lactate dehydrogenase (LDH) as independent risk factors for PE, while albumin (Alb) emerged as a protective factor (p < 0.05).

Conclusions

In pregnant women with PE, the serum levels of THBD and CXCL6 are increased, whereas their expression in placental tissue is decreased. CXCL6 emerges as an independent risk factor for PE, with expression patterns independent of gestational age confounding, while THBD shows PE-specific gestational age-related effects that provide additional insights into disease pathophysiology. These findings indicate that the inflammatory response and insufficient trophoblast invasion may play important roles in the pathogenesis of PE, providing a new theoretical basis for the early diagnosis and targeted intervention of PE.

Purpose

Several studies have evaluated a wide range of immunomodulatory therapies for treatment of unexplained recurrent pregnancy loss (RPL) and granulocyte colony stimulating factor (G-CSF) is a new addition. We aimed to perform a cumulative meta-analysis to update and reevaluate the efficacy of the use of G-CSF to reduce the risk of first trimester miscarriages in women with a history of RPL.

Methods

We searched electronic databases until September 26, 2024. We screened 309 citations and included six randomized control trials (RCTs) and four observational cohort studies. A total of 800 women were included in the analysis for the primary outcome; 426 (53%) women had treatment with G-CSF and 374 (47%) women had placebo or no treatment.

Results

Women who were administered GCSF in early pregnancy had a statistically significant reduction in miscarriage compared to those who had placebo or no treatment, odds ratio [95% CI] = 0.4 [0.3; 0.7]. A subsequent significant increase in live birth was also found in women who had GCSF, odds ratio [95% CI] = 2.3 [1.4; 3.6].

Conclusion

Among women with a history of recurrent pregnancy loss, administration of granulocyte colony stimulating factor resulted in statistically significant reduction in first trimester miscarriage and subsequent improvement in live birth.

Background

Gestational diabetes mellitus (GDM) is a pregnancy-associated metabolic disorder characterized by transient hyperglycemia resulting from impaired insulin sensitivity and β-cell dysfunction. Increasing evidence suggests that inflammatory pathways, particularly the NLRP3 inflammasome and nuclear factor kappa B (NF-κB), play crucial roles in initiating and perpetuating insulin resistance and glucose intolerance during GDM.

Methods

This review comprehensively examines the current literature on the molecular mechanisms linking the NLRP3/NF-κB signaling axis to the development of GDM. Relevant studies were identified through database searches focusing on inflammation-mediated insulin resistance, cytokine regulation, and therapeutic interventions targeting these pathways.

Results

Findings indicate that activation of the NLRP3 inflammasome and NF-κB pathway enhances the production of proinflammatory cytokines, such as IL-1β and TNF-α, which contribute to pancreatic β-cell dysfunction and insulin resistance. Experimental models demonstrate that inhibition of these signaling cascades mitigates inflammation, improves insulin sensitivity, and normalizes glucose metabolism, suggesting their critical involvement in GDM pathogenesis.

Conclusion

The NLRP3/NF-κB axis plays a pivotal role in mediating inflammation and insulin resistance in GDM. Targeting this pathway may offer a promising therapeutic strategy for preventing or managing GDM. However, further research is needed to fully elucidate its molecular interactions and validate potential pharmacological interventions.

Background

This study aimed to characterize the endometrial microbiota in patients with chronic endometritis (CE) after doxycycline treatment and to compare microbial profiles and pregnancy outcomes between treated CE patients and those without CE.

Methods

Fifty-two women undergoing frozen–thawed embryo transfer were enrolled. Based on histopathological findings before oocyte retrieval, patients were categorized into the CE treatment group or the non-CE group. CE patients received doxycycline (100 mg twice daily for 14 days). Endometrial tissue was collected 1 day before endometrial transformation and analyzed by 16S rRNA gene sequencing of the V3–V4 region using QIIME2. Clinical and microbiological outcomes were compared between the groups.

Results

The two groups showed no significant differences in age, body mass index, endometrial thickness, number of embryos transferred, or transfer protocol (p > 0.05). Infertility duration was significantly longer in the CE group (p < 0.05). Alpha-diversity analysis revealed lower microbial richness and diversity in the CE group (p < 0.05). Firmicutes abundance was significantly reduced (p = 0.0214), whereas Bacteroidetes and Planctomycetes were increased (p < 0.05). At the genus level, Lactobacillus remained dominant but was markedly decreased in the CE group (p = 0.0157), while Ralstonia and Methylobacterium were enriched (p < 0.05). The clinical pregnancy rate and biochemical pregnancy rate showed no significant differences between the groups (p > 0.05), but the live birth rate was significantly lower in the CE group (p = 0.036).

Conclusion

Despite histological resolution following doxycycline therapy, CE patients exhibited persistent dysbiosis characterized by decreased Lactobacillus and increased opportunistic taxa, which may impair endometrial receptivity and pregnancy outcomes. These findings suggest that antibiotic therapy alone may not fully restore microbial balance in CE, warranting further investigation into microbiota-targeted interventions to improve reproductive success.