American Journal of Reproductive Immunology最新文献

{"title":"Chronic Endometritis, Uterine Natural Killer Level and Celiac Disease Predisposition in Idiopathic Recurrent Pregnancy Loss","authors":"Inversetti Annalisa,&nbsp;Zambella Enrica,&nbsp;Serena Caterina,&nbsp;Ciliberto Federica,&nbsp;Bertoli Francesca,&nbsp;Morenghi Emanuela,&nbsp;Di Simone Nicoletta,&nbsp;Mecacci Federico","doi":"10.1111/aji.70323","DOIUrl":"10.1111/aji.70323","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Both chronic endometritis (CE) and high levels of uterine Natural Killer (uNK) have been associated to recurrent pregnancy loss (RPL), but a clear causality has not yet been defined. In addition, an increased prevalence of celiac disease (CD) genetic predisposition, defined by HLA-DQ2/DQ8 high risk, has been reported in RPL patients, despite negative serological screening for CD. Recent evidence suggested that HLA-mediated immune mechanisms may contribute to endometrial inflammation. The two main aims of this multicenter retrospective cohort study were to assess the prevalence of CE and high uNK cells level in idiopathic RPL patients with and without HLA-DQ2/DQ8 haplotypes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with at least two prior first trimester miscarriages and negative standard diagnostic work-up for RPL and CD underwent HLA-DQ2/DQ8 genotyping and endometrial biopsy. CE was defined as &gt;5.15 CD 138 positive plasma cells per 10 mm² (1/high-power field). Increased uNK levels were defined as &gt;4.5%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this study, a total of 197 idiopathic RPL patients were included: 92 were HLA-DQ2/DQ8-high risk and 105 were HLA-DQ2/DQ8-low risk. While the prevalence of CE was not significantly different, increased uNK density was significantly more frequent in HLA-DQ2/DQ8 high-risk patients compared to HLA-DQ2/DQ8 low-risk patients (50% vs. 29.7%, <i>p</i> = 0.017). In multiple regression analysis, HLA-DQ2/DQ8 risk was independently associated with high uNK cell levels (aOR 2.25, 95%CI 1.01–5.02, <i>p</i> = 0.049).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings suggest that HLA-mediated immune mechanisms may increase uNK cell levels, potentially impairing embryo implantation. However, a causal relationship cannot be established.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Absence of Receptor Mediated Functional Progesterone Withdrawal in the Decidua During Labor-like Inflammatory Conditions","authors":"Jessica Selim,&nbsp;Tilu Thomas,&nbsp;Rheanna Urrabaz-Garza,&nbsp;Glenmarie Angelica S. Perias,&nbsp;Lauren S. Richardson,&nbsp;Ourlad Alzeus Gaddi Tantengco,&nbsp;Ramkumar Menon","doi":"10.1111/aji.70319","DOIUrl":"10.1111/aji.70319","url":null,"abstract":"<div>\u0000 \u0000 <p><b>Problem</b>: Preterm birth and dysregulated labor remain the leading causes of neonatal morbidity, yet the mechanisms governing progesterone (P4) signaling and inflammatory regulation within the decidua parietalis at the feto-maternal interface are poorly understood. In particular, the roles of progesterone receptor membrane components PGRMC1 and PGRMC2 in maintaining decidual immune homeostasis during pregnancy and labor remain undefined.</p>\u0000 <p><b>Methods</b>: of Study:Human decidua parietalis cells were cultured under pregnancy- and labor-like conditions, with and without immune cell co-culture. Expression of PGRMC1, PGRMC2, and PR-A/B and their interaction with P4 were assessed. Labor-associated inflammation was modeled using lipopolysaccharide (LPS). SiRNA targeted knockdown of PGRMC2 was performed to evaluate effects on progesterone receptor expression, cell-cycle progression, progesterone metabolism (AKR1C1/2) and inflammatory cytokine production.</p>\u0000 <p><b>Results</b>: PGRMC1, PGRMC2, and PR-A/B expression remained stable across gestational conditions, and P4 robustly interacted with PGRMCs. LPS-induced inflammation was not suppressed by P4 despite preserved receptor expression. PGRMC2 knockdown did not alter progesterone receptor expression, cell-cycle progression, or progesterone metabolism; however, it significantly increased baseline and stimulus-induced IL-6 and TNF levels. Under labor-like inflammatory conditions, loss of PGRMC2 markedly amplified cytokine production.</p>\u0000 <p><b>Conclusions</b>: These findings identify PGRMC2 as an important regulator of decidual immune homeostasis; however, the translational relevance of this role remains limited, as neither our pregnancy nor labor models produced a physiologically meaningful downregulation of PGRMC2 expression. Instead, our data support a model in which parturition-associated changes in decidua are driven primarily by inflammatory cues rather than by loss of progesterone receptor signaling, demonstrating tissue-specific progesterone signaling.</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148981989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcifediol Suppressed Placental Inflammation and Improved Pregnancy Outcomes by Targeting JAK/STAT Signaling Pathway in Preeclampsia","authors":"Mengxue Wu,&nbsp;Jing Cai,&nbsp;Jian Shen,&nbsp;Yu Zhen","doi":"10.1111/aji.70306","DOIUrl":"10.1111/aji.70306","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Preeclampsia (PE) is a pregnancy-specific syndrome, which has been recognized as a leading cause of maternal and neonatal morbidity and mortality worldwide. Calcifediol (25-hydroxy Vitamin D3) was reported to be closely associated with pregnancy outcomes such as preeclampsia, gestational hypertension, and gestational diabetes. Nevertheless, the specific role of calcifediol remains obscure in PE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The pregnant rats were treated with L-NAME (50 mg/kg/day) to establish PE models. Histopathological injury of placental tissues was observed by HE staining. Systolic blood pressure, proteinuria, and urine volume were measured to evaluate the symptoms of PE. The neonatal birth rate, pup's body length and weight were determined to assess pregnancy outcomes. The placental cytokines and serum sFlt-1/PIGF ratio were detected by ELISA analysis. The protein levels were measured by Western blotting analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Calcifediol treatment alleviated the histopathological injury placental tissues of PE rats. In addition, calcifediol improves PE symptoms by attenuating hypertension, proteinuria and urine volume. Besides, calcifediol ameliorated pregnancy outcomes by enhancing live birth rate, neonatal birth length, and neonatal birth weight. Moreover, calcifediol restrained pro-inflammatory cytokines in placental tissues and facilitated serum sFlt-1/PIGF balance in PE rats. Mechanistically, calcifediol is closely associated with the inactivation of JAK/STAT signaling, as evidenced by the reduction of the phosphorylated JAK1, STAT1, and STAT3 proteins in placental tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Calcifediol elicits significant therapeutic effects in L-NAME-induced PE rat models by ameliorating PE symptoms and pregnancy outcomes, attenuating inflammatory responses and alleviating histopathological damage.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation-Targeted Endometriosis Research Needs Pain, Mood, and Fertility-Priority Outcomes","authors":"Yi-Hsin Chiang,&nbsp;Lien-Chung Wei","doi":"10.1111/aji.70320","DOIUrl":"10.1111/aji.70320","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulatory Effects of Tokishakuyakusan on Progesterone Withdrawal–Induced Uterine Inflammation in Pregnant Mice","authors":"Takeshi Nagamatsu,&nbsp;Manami Yanagisawa,&nbsp;Yohei Tokita,&nbsp;Keisuke Nakajima,&nbsp;Tomohiro Otani,&nbsp;Ayumi Taguchi,&nbsp;Mari Ichinose,&nbsp;Keiich Kumasawa,&nbsp;Takayuki Iriyama","doi":"10.1111/aji.70318","DOIUrl":"10.1111/aji.70318","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Tokishakuyakusan (TSS) is a traditional Japanese Kampo medicine widely used to support pregnancy; however, its molecular mechanisms remain poorly understood. This study aimed to elucidate the progesterone-related immunomodulatory mechanisms underlying the pregnancy-supportive effects of TSS using a mouse model of progesterone withdrawal induced by mifepristone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Pregnant mice were fed either a control diet or a diet containing 1% TSS from mating until late gestation. On day 15 postcoitus, all mice received low-dose mifepristone to induce functional progesterone withdrawal. Cytokine and chemokine profiles in serum, corpus uteri, and placenta were analyzed using multiplex assays, and uterine expression of progesterone-responsive and inflammatory genes were evaluated by real-time RT-PCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Mifepristone administration induced a systemic proinflammatory response, characterized by increased serum levels of G-CSF, IL-6, KC, and MCP-1. TSS administration increased G-CSF without affecting fetal number, fetal weight, or placental weight. In the corpus uteri, TSS significantly suppressed IL-6 protein expression, whereas placental cytokine profiles were largely unaffected. Furthermore, TSS significantly increased uterine mRNA expression of the progesterone-responsive anti-inflammatory molecules secretory leukocyte peptidase inhibitor (SLPI) and progranulin (PGRN).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings suggest that TSS mitigates inflammation associated with progesterone withdrawal by suppressing uterine IL-6 and increasing the expression of progesterone-responsive anti-inflammatory molecules such as SLPI and PGRN. These findings suggest that TSS may modulate progesterone-responsive anti-inflammatory pathways through increased expression of SLPI and PGRN while suppressing uterine IL-6.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13544994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Common Therapies for Threatened Preterm Labor on the Placental Inflammatory Response","authors":"Jessica Weng,&nbsp;Francisco Cortina,&nbsp;Suyun Ling,&nbsp;Sylvie Girard","doi":"10.1111/aji.70316","DOIUrl":"10.1111/aji.70316","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Patients with threatened preterm labor (PTL) are treated with antibiotics, corticosteroids, and magnesium sulfate to mitigate infection, promote fetal lung maturation, provide fetal neuroprotection and overall minimize the impact of prematurity on the neonate. However, the effect of these drugs on the placental inflammatory profile is unknown even though these are given systemically and reach the placenta. We evaluated their action in an <i>ex vivo</i> model of placental inflammation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Placental explants from uncomplicated pregnancies were exposed to lipopolysaccharide (LPS) ± azithromycin, betamethasone, and/or magnesium sulfate. Production (lysate) and secretion (supernatant) of pro- and anti-inflammatory cytokines were assessed by ELISA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both pro- and anti-inflammatory cytokines were increased by LPS versus untreated. Azithromycin, or magnesium sulfate did not alter the inflammatory profile by themselves nor when added at the same time or 24 h after LPS. Betamethasone decreased both pro- and anti-inflammatory cytokines only when administered at the same time as LPS, without any effects if delayed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Therapeutic interventions classically used for preterm labor (PTL) do not impact the placental inflammatory profile by themselves or in the context of an <i>ex vivo</i> placental explants model of LPS-induced inflammation, except for betamethasone when administered concurrently with LPS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feto–Maternal Microchimerism and the Brain: Mechanisms, Neurological Implications, and Translational Perspectives","authors":"Nosarieme O. Abey","doi":"10.1111/aji.70317","DOIUrl":"10.1111/aji.70317","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Microchimerism in the brain is a common phenomenon, where in cells cross between mother and fetus during pregnancy, and persist for decades. It has been studied primarily within reproductive immunology and transplantation medicine. The relevance of microchimerism to central nervous system biology, neurological disease, and experimental chimeric modelling has received comparatively little systematic attention. This review sought evidence across the biology of feto–maternal microchimerism, its association with neurological disease, and the emerging field of experimental chimeric brain modelling, to extrapolate a cohesive mechanistic framework.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>Research articles in reproductive immunology, neurodevelopment, and neurodegeneration were gathered to assess the potential roles of fetal microchimeric cells (FMc) in brain health and disease. By combining natural microchimerism with experimental chimeric models, a framework for understanding how nonself cells influence the maternal brain was extrapolated and critical mechanisms identified. Searches were conducted across PubMed/MEDLINE, Scopus, and Google Scholar using a dual-concept Boolean.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The literature reviews show that microchimeric cells cross the blood-brain barrier (BBB), adopt neural and glial phenotypes in the maternal brain parenchyma, and exhibit injury-responsive recruitment in preclinical models. Reciprocally, maternal microchimeric cells (MMc) are present in the offspring brain, where they have been found adopting neural and immune-lineage phenotypes in experimental models. These findings raise the possibility that bidirectional microchimerism influences susceptibility to neurological disease, modulates neuroimmune signaling, and contributes to endogenous repair, although causal mechanisms remain unresolved. Experimental chimeric brain models have extended these principles into therapeutic contexts. Establishing the functional mechanism and directionality requires more prospective longitudinal cohort studies and transcriptional profiling at single-cell resolution in microchimeric brain-resident populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"Interleukin-6 Downregulates T Helper 17 Cytokines via Indoleamine 2,3-Dioxygenase 1 at the Maternal-Fetal Interface\"","authors":"","doi":"10.1111/aji.70304","DOIUrl":"https://doi.org/10.1111/aji.70304","url":null,"abstract":"<p>X. Tang, S. Dao, J. Luo, et al., “Interleukin-6 Downregulates T Helper 17 Cytokines via Indoleamine 2,3-Dioxygenase 1 at the Maternal-Fetal Interface,” <i>American Journal of Reproductive Immunology</i> 96, no. 1 (2026): e70289, https://doi.org/10.1111/aji.70289.</p><p>Description of error</p><p>We apologize for these errors.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70304","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148856698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Placental Extracellular Vesicles in Preeclampsia: Molecular Cargo, Pathophysiological Roles, and Emerging Diagnostic and Therapeutic Frontiers","authors":"Marhaen Hardjo,&nbsp;Alfi Sophian","doi":"10.1111/aji.70315","DOIUrl":"https://doi.org/10.1111/aji.70315","url":null,"abstract":"<div>\u0000 \u0000 <p>Preeclampsia (PE) affects 2%–8% of pregnancies globally and remains a leading cause of maternal and perinatal mortality. A central clinical gap is the absence of analytically and clinically validated non-invasive biomarkers capable of predicting PE before symptom onset. Current clinical tools, including angiogenic markers (sFlt-1/PlGF ratio) and first-trimester risk algorithms, have limitations that underscore the need for complementary approaches. Placental extracellular vesicles (EVs)—small particles released predominantly by syncytiotrophoblast cells—are implicated across PE pathophysiology. Circulating total small EV (sEV) concentrations, typically 30–150 nm and isolated by differential centrifugation or size-exclusion chromatography, are measurably elevated in maternal circulation from the first trimester in women who develop PE; this operational, size- and isolation-based definition does not by itself establish placental origin, which requires placental-attribution markers (e.g., PLAP, syncytins) discussed in Section 2. Their molecular cargo, encompassing microRNAs (miR-210, miR-15a-5p, miR-520a-5p, miR-146a-5p, miR-93-5p), anti-angiogenic proteins (sFlt-1, sEng), and hypoxia markers (HIF-1α), reflects placental pathophysiology. Recent evidence has expanded the known pathophysiological reach of placental EVs: beyond endothelial dysfunction and angiogenic imbalance, they are now implicated in blood-brain barrier disruption via claudin-5 (CLDN5) downregulation, supporting a plausible mechanistic link to neurological complications of PE. Proteomic profiling of EV fractions identifies molecularly distinct PE subtypes, enabling investigational subtype discrimination beyond current clinical criteria. Recent in vivo proof-of-concept evidence in a rat model demonstrates that amniotic fluid-derived EV-associated miR-146a-5p ameliorates PE phenotypes, opening a preclinical therapeutic avenue. This narrative review synthesises evidence from a structured PubMed/MEDLINE and Scopus search covering 2017–March 2025 on placental EV biogenesis, cargo heterogeneity, immune modulation, organ-specific pathological consequences, and translational potential as first-trimester liquid biopsy candidates. Methodological standardization challenges and future research priorities are discussed.</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148856697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Gestational Maternal SARS-CoV-2 Infection on Neonatal Inflammatory Biomarkers","authors":"Bushra Amreen,&nbsp;Floriana Milazzo,&nbsp;Frederieke Gigase,&nbsp;Darwin D'souza,&nbsp;Natalie Samper,&nbsp;Joseph Thomas Martin,&nbsp;Seunghee Kim-Schulze,&nbsp;Whitney Lieb,&nbsp;Lot D. de Witte,&nbsp;Veerle Bergink,&nbsp;Jia Chen,&nbsp;Corina Lesseur,&nbsp;Anna-Sophie Rommel","doi":"10.1111/aji.70313","DOIUrl":"10.1111/aji.70313","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Since the beginning of the pandemic, millions of pregnant women have been exposed to SARS-CoV-2, eliciting concerns about maternal and fetal sequelae. Yet, the impact of SARS-CoV-2 on the child's immune response remains largely unexplored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Herein, we leverage 833 mother-infant dyads from a New York City-based pregnancy cohort to explore prospective associations between maternal gestational SARS-CoV-2 infection and inflammatory biomarkers in newborns. Of the mothers, 100 were infected with SARS-CoV-2 during pregnancy, as confirmed through self-report, antibody and/or PCR test results. We obtained 92 inflammatory biomarker levels in neonatal dried blood spots (DBS) using the Olink Target 96 Inflammation panel. An empirical Bayes method was used to fit linear regression models to assess the effects of maternal infection during pregnancy on neonatal inflammatory markers at birth. We also conducted stratified analyses by timing of infection in early (&lt;20 weeks) versus late (≥20 weeks) gestation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Higher levels of 22 inflammatory biomarkers, including CD5, TNFSF14, CD8a, TGF-α, and CD244, were observed in neonates prenatally exposed to SARS-CoV-2 compared to unexposed neonates (<i>p_adj</i> &lt; 0.05). Early-gestation infection was associated with increased levels of eight inflammatory biomarkers, including TNFSF14, TGF-α and decreased IL-18 levels, while late-gestation infection was linked to elevations in 12 biomarkers, including CD5, CD6, PD-L1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results indicate that maternal SARS-CoV-2 infection during pregnancy influences inflammatory biomarkers in newborns, with the timing of infection playing a critical role in determining these immune profiles. Thus, this study emphasizes the need for further research and long-term follow-up to examine future health consequences for the child.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}