Journal of Reproductive Immunology最新文献

Mendelian randomization reveals causal relationships between cytokines and male reproductive diseases

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-02-25 DOI: 10.1016/j.jri.2025.104465

Jie Ding

This study aims to explore the causal links between cytokines and four male reproductive disorders, namely abnormal spermatozoa (AS), male infertility, erectile dysfunction (ED), and hyperplasia of prostate (HP), employing a two-sample Mendelian randomization (MR) approach. Genetic associations with male reproductive diseases were derived from the IEU OpenGWAS project, with cytokine data from two GWASs focused on the human proteome and cytokines. Estimations were derived using inverse variance weighting, MR-Egger regression, weighted median, weighted model, and simple mode. Furthermore, the robustness of the findings was evaluated through Cochran’s Q-test, MR-Egger regression, and leave-one-out sensitivity analysis. Fifteen unique cytokines were identified as having causal relationships with the risk of four male reproductive disorders. Specifically, for AS, interleukin-22 (IL-22), IL-12, and macrophage migration inhibitory factor were negatively correlated with AS, while tumor necrosis factor β levels were positively correlated with AS. In the context of male infertility, IL-2 receptor antagonist levels, IL-34, and granulocyte-colony stimulating factor levels were positively linked to male infertility, whereas IL-21 showed a negative relationship. Regarding ED, IL-19, IL-1β, and eotaxin levels were negatively associated with ED risk, while macrophage inflammatory protein 1β (MIP-1β) levels and interferon gamma-induced protein 10 levels were positively associated. As for HP, stromal-cell-derived factor 1α levels and MIP-1α levels revealed negative associations with HP. In conclusion, this MR analysis revealed that several cytokines were causally associated with male reproductive diseases and could be valuable in offering new insights for further mechanistic and clinical investigations of cytokines-associated male reproductive diseases.

{"title":"Mendelian randomization reveals causal relationships between cytokines and male reproductive diseases","authors":"Jie Ding","doi":"10.1016/j.jri.2025.104465","DOIUrl":"10.1016/j.jri.2025.104465","url":null,"abstract":"<div><div>This study aims to explore the causal links between cytokines and four male reproductive disorders, namely abnormal spermatozoa (AS), male infertility, erectile dysfunction (ED), and hyperplasia of prostate (HP), employing a two-sample Mendelian randomization (MR) approach. Genetic associations with male reproductive diseases were derived from the IEU OpenGWAS project, with cytokine data from two GWASs focused on the human proteome and cytokines. Estimations were derived using inverse variance weighting, MR-Egger regression, weighted median, weighted model, and simple mode. Furthermore, the robustness of the findings was evaluated through Cochran’s Q-test, MR-Egger regression, and leave-one-out sensitivity analysis. Fifteen unique cytokines were identified as having causal relationships with the risk of four male reproductive disorders. Specifically, for AS, interleukin-22 (IL-22), IL-12, and macrophage migration inhibitory factor were negatively correlated with AS, while tumor necrosis factor β levels were positively correlated with AS. In the context of male infertility, IL-2 receptor antagonist levels, IL-34, and granulocyte-colony stimulating factor levels were positively linked to male infertility, whereas IL-21 showed a negative relationship. Regarding ED, IL-19, IL-1β, and eotaxin levels were negatively associated with ED risk, while macrophage inflammatory protein 1β (MIP-1β) levels and interferon gamma-induced protein 10 levels were positively associated. As for HP, stromal-cell-derived factor 1α levels and MIP-1α levels revealed negative associations with HP. In conclusion, this MR analysis revealed that several cytokines were causally associated with male reproductive diseases and could be valuable in offering new insights for further mechanistic and clinical investigations of cytokines-associated male reproductive diseases.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104465"},"PeriodicalIF":2.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512287","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}

引用次数: 0

The role of necroptosis in pathological pregnancies: Mechanisms and therapeutic opportunities

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-02-25 DOI: 10.1016/j.jri.2025.104460

Lidan He , Shan Zheng , Feng Zhan , Na Lin

Necroptosis, a distinctive form of programmed cell death differs mechanistically from apoptosis pyroptosis, and autophagy, is characterized by the activation of receptor-interacting protein kinases (RIPK1/RIPK3) and their downstream effector, mixed lineage kinase domain-like protein (MLKL). This programmed cell death pathway serves as a crucial mediator of inflammatory responses and has been implicated in the pathogenesis of diverse pathological conditions. Recent evidence has implicated dysregulated necroptosis in the pathogenesis of severe pregnancy complications, including preeclampsia (PE), fetal growth restriction (FGR), recurrent spontaneous abortion (RSA), and gestational diabetes mellitus (GDM). In these disorders, necroptosis promotes placental dysfunction through multiple interconnected mechanisms: amplification of pro-inflammatory cytokine cascades, aberrant immune activation, disruption of plasma membrane integrity, and subsequent tissue injury.These pregnancy-related pathologies consistently demonstrate elevated necroptotic signatures, correlating with adverse maternal-fetal outcomes. This comprehensive review synthesizes current understanding of the molecular mechanisms underlying necroptosis, with particular emphasis on its pivotal role in the etiopathogenesis of pregnancy-related disorders. Furthermore, we critically evaluate the therapeutic potential of targeting the necroptotic signaling axis, providing novel perspectives for developing targeted interventions to improve clinical outcomes in complicated pregnancies.

{"title":"The role of necroptosis in pathological pregnancies: Mechanisms and therapeutic opportunities","authors":"Lidan He , Shan Zheng , Feng Zhan , Na Lin","doi":"10.1016/j.jri.2025.104460","DOIUrl":"10.1016/j.jri.2025.104460","url":null,"abstract":"<div><div>Necroptosis, a distinctive form of programmed cell death differs mechanistically from apoptosis pyroptosis, and autophagy, is characterized by the activation of receptor-interacting protein kinases (RIPK1/RIPK3) and their downstream effector, mixed lineage kinase domain-like protein (MLKL). This programmed cell death pathway serves as a crucial mediator of inflammatory responses and has been implicated in the pathogenesis of diverse pathological conditions. Recent evidence has implicated dysregulated necroptosis in the pathogenesis of severe pregnancy complications, including preeclampsia (PE), fetal growth restriction (FGR), recurrent spontaneous abortion (RSA), and gestational diabetes mellitus (GDM). In these disorders, necroptosis promotes placental dysfunction through multiple interconnected mechanisms: amplification of pro-inflammatory cytokine cascades, aberrant immune activation, disruption of plasma membrane integrity, and subsequent tissue injury.These pregnancy-related pathologies consistently demonstrate elevated necroptotic signatures, correlating with adverse maternal-fetal outcomes. This comprehensive review synthesizes current understanding of the molecular mechanisms underlying necroptosis, with particular emphasis on its pivotal role in the etiopathogenesis of pregnancy-related disorders. Furthermore, we critically evaluate the therapeutic potential of targeting the necroptotic signaling axis, providing novel perspectives for developing targeted interventions to improve clinical outcomes in complicated pregnancies.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104460"},"PeriodicalIF":2.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512288","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}

引用次数: 0

Endometriosis: A new perspective on epigenetics and oxidative stress

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-02-21 DOI: 10.1016/j.jri.2025.104462

Yu Guan , Yawen Chen , Rong Lin , Tinghui Mo , Shiyu Li , Ying Cao , Tailang Yin , Lianghui Diao , Yuye Li

As a complex chronic gynecological disorder characterized by multifaceted etiology involving genetics, environment, immunity and inflammation, endometriosis (EM) has long been a significant concern for women of reproductive age worldwide. This review aimed to comprehensively examine the interplay between epigenetics and oxidative stress (OS) in the pathogenesis of EM. Through the integration of cutting-edge research, the response of OS signals to epigenetic modifications was explored. The microbiome exerts an influence on this causal regulatory relationship, and these mechanisms collectively contribute to the pathophysiology of EM. Specifically, this article highlighted the roles of epigenetics and OS in EM and underscored the importance of the microbiome as a regulatory link. A discussion was also held on the future directions of biomarkers and precision medicine, including the application prospects of epigenetic and OS markers in the diagnosis and treatment decision-making of EM, and innovations in therapeutic strategies like targeting epigenetic modifications and antioxidant therapies. Moreover, this review emphasized the potential of multi-omics integrated analysis to deepen the understanding of the disease, guide future therapeutic strategies and promote personalized medicine.

{"title":"Endometriosis: A new perspective on epigenetics and oxidative stress","authors":"Yu Guan , Yawen Chen , Rong Lin , Tinghui Mo , Shiyu Li , Ying Cao , Tailang Yin , Lianghui Diao , Yuye Li","doi":"10.1016/j.jri.2025.104462","DOIUrl":"10.1016/j.jri.2025.104462","url":null,"abstract":"<div><div>As a complex chronic gynecological disorder characterized by multifaceted etiology involving genetics, environment, immunity and inflammation, endometriosis (EM) has long been a significant concern for women of reproductive age worldwide. This review aimed to comprehensively examine the interplay between epigenetics and oxidative stress (OS) in the pathogenesis of EM. Through the integration of cutting-edge research, the response of OS signals to epigenetic modifications was explored. The microbiome exerts an influence on this causal regulatory relationship, and these mechanisms collectively contribute to the pathophysiology of EM. Specifically, this article highlighted the roles of epigenetics and OS in EM and underscored the importance of the microbiome as a regulatory link. A discussion was also held on the future directions of biomarkers and precision medicine, including the application prospects of epigenetic and OS markers in the diagnosis and treatment decision-making of EM, and innovations in therapeutic strategies like targeting epigenetic modifications and antioxidant therapies. Moreover, this review emphasized the potential of multi-omics integrated analysis to deepen the understanding of the disease, guide future therapeutic strategies and promote personalized medicine.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104462"},"PeriodicalIF":2.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487601","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}

引用次数: 0

Chebulagic acid inhibits lipopolysaccharide-induced endometritis by regulating mitogen-activated protein kinase/nuclear factor-κB signaling

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-02-21 DOI: 10.1016/j.jri.2025.104464

Xinyu Liu , Zhiguo Gong , Ying Yang , Jinzhong Dong , Lanxin Zhang , Zhengyi Li , Feifan Zhao , Jianbing Zhang , Ruifeng Gao

This study investigates the potential protective effects of chebulagic acid (CA) against endometritis and its underlying molecular mechanisms. Network pharmacology analysis identified 19 potential targets of CA related to endometritis, mainly associated with the mitogen-activated protein kinase (MAPK) signaling pathways. Molecular docking analysis further indicated that MAPK14 and MAPK3 are critical targets of CA, suggesting its potential role in modulating inflammatory responses. In vitro experiments demonstrated that CA at concentrations of 12.5, 25, and 50 µg/mL significantly inhibited the secretion of proinflammatory cytokines interleukin (IL)-1β and IL-6 in lipopolysaccharide (LPS)-stimulated bovine endometrial epithelial cells (bEECs), without affecting cell viability. In vivo, CA treatment mitigated uterine inflammation in an LPS-induced mouse model of endometritis by downregulating high-mobility group box protein 1 (HMGB1) expression and inhibiting the phosphorylation of key signaling molecules, including p65, extracellular signal-regulated kinase (ERK), and p38. These findings suggest that CA exerts significant anti-inflammatory effects in endometritis by modulating the MAPK/NF-κB signaling pathway. Given its potential to suppress excessive inflammatory responses, CA may serve as a promising candidate for the development of novel therapeutic strategies for endometritis.

{"title":"Chebulagic acid inhibits lipopolysaccharide-induced endometritis by regulating mitogen-activated protein kinase/nuclear factor-κB signaling","authors":"Xinyu Liu , Zhiguo Gong , Ying Yang , Jinzhong Dong , Lanxin Zhang , Zhengyi Li , Feifan Zhao , Jianbing Zhang , Ruifeng Gao","doi":"10.1016/j.jri.2025.104464","DOIUrl":"10.1016/j.jri.2025.104464","url":null,"abstract":"<div><div>This study investigates the potential protective effects of chebulagic acid (CA) against endometritis and its underlying molecular mechanisms. Network pharmacology analysis identified 19 potential targets of CA related to endometritis, mainly associated with the mitogen-activated protein kinase (MAPK) signaling pathways. Molecular docking analysis further indicated that MAPK14 and MAPK3 are critical targets of CA, suggesting its potential role in modulating inflammatory responses. <em>In vitro</em> experiments demonstrated that CA at concentrations of 12.5, 25, and 50 µg/mL significantly inhibited the secretion of proinflammatory cytokines interleukin (IL)-1β and IL-6 in lipopolysaccharide (LPS)-stimulated bovine endometrial epithelial cells (bEECs), without affecting cell viability. <em>In vivo</em>, CA treatment mitigated uterine inflammation in an LPS-induced mouse model of endometritis by downregulating high-mobility group box protein 1 (HMGB1) expression and inhibiting the phosphorylation of key signaling molecules, including p65, extracellular signal-regulated kinase (ERK), and p38. These findings suggest that CA exerts significant anti-inflammatory effects in endometritis by modulating the MAPK/NF-κB signaling pathway. Given its potential to suppress excessive inflammatory responses, CA may serve as a promising candidate for the development of novel therapeutic strategies for endometritis.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104464"},"PeriodicalIF":2.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479410","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}

引用次数: 0

Do progesterone receptor membrane components (PGRMC)s play a role in the chorions refractoriness to epithelial-to-mesenchymal transition (EMT)?

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-02-21 DOI: 10.1016/j.jri.2025.104463

B. Bush , L.S. Richardson , E. Radnaa , F. Behnia , J. Jacob , R.C.V. Lintao , R. Menon

Fetal membrane inflammation is one of the drivers of adverse pregnancy outcomes. One of the reported pathways of inflammation is epithelial-mesenchymal transition (EMT) of amniotic epithelial cells. EMT is resisted during gestation via signaling initiated by the binding of progesterone (P4) to progesterone receptor membrane components (PGRMC1/PGRMC2). The vulnerability of chorionic trophoblast cells (CTCs) to transition has not been studied. Here, we examined CTCs EMT in response to the stressors and the role of PGRMC1/PGRMC2. CTCs were treated with the autophagy inhibitor bafilomycin (Baf), transforming growth factor beta (TGF-β, EMT-inducer), and lipopolysaccharide (LPS) to simulate cellular stressors associated with an adverse pregnancy environment. The primary endpoints included morphological evidence of EMT, N-cadherin-to-E-cadherin ratio, vimentin/cytokeratin staining, pro-inflammatory cytokine and P4 production. PGRMC1/PGRMC2 knock-out (KO) CTCs were prepared using CRISPR/Cas9, and experiments were repeated to test the influence of the P4–PGRMC axis. Wild-type CTCs were resistant to cellular transitions, changes in P4 production, and shifts in the inflammatory status under normal, LPS, or TGF-β conditions. Autophagy inhibition tended to cause CTCs to transition (morphological changes; high N-cadherin-to-E-cadherin ratio [p < 0.05], no change in vimentin/cytokeratin), though a complete transition was not evident. Further, neither PGRMC1/PGRMC2 played a role in CTC cellular transitions, as their KO did not cause any major changes. Chorion cells resist EMT to minimize inflammation and to maintain their barrier functions regardless of the presence of PGRMC1/ PGRMC2. Cellular stressors or infectious antigens are likely to impact the amnion, where membrane weakening can be initiated.

{"title":"Do progesterone receptor membrane components (PGRMC)s play a role in the chorions refractoriness to epithelial-to-mesenchymal transition (EMT)?","authors":"B. Bush , L.S. Richardson , E. Radnaa , F. Behnia , J. Jacob , R.C.V. Lintao , R. Menon","doi":"10.1016/j.jri.2025.104463","DOIUrl":"10.1016/j.jri.2025.104463","url":null,"abstract":"<div><div>Fetal membrane inflammation is one of the drivers of adverse pregnancy outcomes. One of the reported pathways of inflammation is epithelial-mesenchymal transition (EMT) of amniotic epithelial cells. EMT is resisted during gestation via signaling initiated by the binding of progesterone (P4) to progesterone receptor membrane components (PGRMC1/PGRMC2). The vulnerability of chorionic trophoblast cells (CTCs) to transition has not been studied. Here, we examined CTCs EMT in response to the stressors and the role of PGRMC1/PGRMC2. CTCs were treated with the autophagy inhibitor bafilomycin (Baf), transforming growth factor beta (TGF-β, EMT-inducer), and lipopolysaccharide (LPS) to simulate cellular stressors associated with an adverse pregnancy environment. The primary endpoints included morphological evidence of EMT, N-cadherin-to-E-cadherin ratio, vimentin/cytokeratin staining, pro-inflammatory cytokine and P4 production. PGRMC1/PGRMC2 knock-out (KO) CTCs were prepared using CRISPR/Cas9, and experiments were repeated to test the influence of the P4–PGRMC axis. Wild-type CTCs were resistant to cellular transitions, changes in P4 production, and shifts in the inflammatory status under normal, LPS, or TGF-β conditions. Autophagy inhibition tended to cause CTCs to transition (morphological changes; high N-cadherin-to-E-cadherin ratio [p < 0.05], no change in vimentin/cytokeratin), though a complete transition was not evident. Further, neither PGRMC1/PGRMC2 played a role in CTC cellular transitions, as their KO did not cause any major changes. Chorion cells resist EMT to minimize inflammation and to maintain their barrier functions regardless of the presence of PGRMC1/ PGRMC2. Cellular stressors or infectious antigens are likely to impact the amnion, where membrane weakening can be initiated.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104463"},"PeriodicalIF":2.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474503","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}

引用次数: 0

A narrative review on MicroRNA's role in diagnosis and therapy of equine endometritis

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-02-19 DOI: 10.1016/j.jri.2025.104459

Sana Asif , Muhammad Wasif Gulzar

Endometritis is a significant cause of infertility in mare. Some infectious agents disrupt the endometrium's innate immune system, resulting in a prolonged systemic inflammatory response that circulates via the blood or cellular degeneration, which ultimately leads to endometritis from bacterial endotoxins. Numerous biological processes use various small, non-coding RNA molecules called MicroRNAs. MicroRNAs (miRNAs) regulate gene expression after transcription by blocking transcription and translation. This manuscript examines patho-morphological discoveries in equine endometritis, the expression and effects of eca-miR-17, eca-miR-223, eca-miR-200a, eca-miR-155, and eca-miR-205, and the therapeutic function of miRNA in endometritis. MiRNAs play a crucial role in controlling inflammatory disorders by modulating cytokine signaling pathways. This review emphasizes the demand for cutting-edge genetic technologies and the development of novel pharmaceutical preparations to improve our understanding of the genes encoding by these miRNAs. It also focuses on the efficacy of miRNAs for control, early diagnosis, and prevention of endometritis.

子宫内膜炎是导致母马不孕的一个重要原因。一些感染性病原体会破坏子宫内膜的先天免疫系统，导致长时间的全身炎症反应，经血液循环或细胞变性，最终导致细菌内毒素引起的子宫内膜炎。许多生物过程都会用到各种称为 MicroRNA 的非编码 RNA 小分子。微RNA（miRNA）通过阻断转录和翻译来调节转录后的基因表达。本手稿研究了马子宫内膜炎的病理形态学发现，eca-miR-17、eca-miR-223、eca-miR-200a、eca-miR-155 和 eca-miR-205 的表达和作用，以及 miRNA 在子宫内膜炎中的治疗功能。MiRNA 通过调节细胞因子信号通路在控制炎症性疾病中发挥着至关重要的作用。本综述强调了对尖端基因技术和新型药物制剂开发的需求，以增进我们对这些 miRNA 编码基因的了解。本综述还重点探讨了 miRNA 在控制、早期诊断和预防子宫内膜炎方面的功效。

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引用次数: 0

Assessing the impact and risk of immunomodulatory compounds on pregnancy

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-02-16 DOI: 10.1016/j.jri.2025.104453

Joanne Kwak-Kim , Curtis C. Maier , Caren M. Villano , Christopher J. Bowman , Frank R. Brennan , Dinesh Stanislaus , Aimee Hillegas , John Krayer , Rodney A. Prell , Tracey L. Papenfuss , Annick Cauvin , Joshua Gamse , Anna Dahlman , Brian Enright , Lawrence Leshin , Gautham K. Rao , Whitney Helms , Claudette L. Fuller , Xiuhua Yang , Connie Chen , Shermaine Mitchell-Ryan

There have been remarkable advancements in understanding the complex and dynamic immune biological processes engaged during all stages of pregnancy. Exquisite control of immune processes is critical to successful outcome in all stages of pregnancy from ovulation to birth. There are many immunomodulatory therapeutics that may offer beneficial treatment options for a variety of diseases (e.g., inflammation/autoimmunity, cancer) to patients that are or desire to become pregnant. It is important to understand the potential for these immunomodulatory therapeutics to alter the critical immune processes in pregnancy to inform clinical risk relative to successful pregnancy. The Health and Environmental Sciences Institute-Developmental and Reproductive Toxicology/Immuno-safety Technical Committee (HESI DART/ITC) conducted a survey on approaches to assess adverse pregnancy outcomes with immunomodulators. HESI DART/ITC also organized a workshop for an extended discussion on immune mechanisms during pregnancy, the adequacy of current tools/methodologies to identify concerns for potential pregnancy hazards from immunomodulatory therapies, ways to identify and address scientific gaps, and global regulatory considerations across various immunomodulatory modalities and indications. In this manuscript we summarize learnings from these efforts to characterize risk within this patient population, promote more informed treatment decisions, and enable safer pharmacological interventions during pregnancy.

{"title":"Assessing the impact and risk of immunomodulatory compounds on pregnancy","authors":"Joanne Kwak-Kim , Curtis C. Maier , Caren M. Villano , Christopher J. Bowman , Frank R. Brennan , Dinesh Stanislaus , Aimee Hillegas , John Krayer , Rodney A. Prell , Tracey L. Papenfuss , Annick Cauvin , Joshua Gamse , Anna Dahlman , Brian Enright , Lawrence Leshin , Gautham K. Rao , Whitney Helms , Claudette L. Fuller , Xiuhua Yang , Connie Chen , Shermaine Mitchell-Ryan","doi":"10.1016/j.jri.2025.104453","DOIUrl":"10.1016/j.jri.2025.104453","url":null,"abstract":"<div><div>There have been remarkable advancements in understanding the complex and dynamic immune biological processes engaged during all stages of pregnancy. Exquisite control of immune processes is critical to successful outcome in all stages of pregnancy from ovulation to birth. There are many immunomodulatory therapeutics that may offer beneficial treatment options for a variety of diseases (e.g., inflammation/autoimmunity, cancer) to patients that are or desire to become pregnant. It is important to understand the potential for these immunomodulatory therapeutics to alter the critical immune processes in pregnancy to inform clinical risk relative to successful pregnancy. The Health and Environmental Sciences Institute-Developmental and Reproductive Toxicology/Immuno-safety Technical Committee (HESI DART/ITC) conducted a survey on approaches to assess adverse pregnancy outcomes with immunomodulators. HESI DART/ITC also organized a workshop for an extended discussion on immune mechanisms during pregnancy, the adequacy of current tools/methodologies to identify concerns for potential pregnancy hazards from immunomodulatory therapies, ways to identify and address scientific gaps, and global regulatory considerations across various immunomodulatory modalities and indications. In this manuscript we summarize learnings from these efforts to characterize risk within this patient population, promote more informed treatment decisions, and enable safer pharmacological interventions during pregnancy.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104453"},"PeriodicalIF":2.9,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479519","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}

引用次数: 0

Placental volume as a potential early marker for metabolic pertubations during pregnancy

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-02-15 DOI: 10.1016/j.jri.2025.104456

Ann-Christin Tallarek , Angelo Sirico , Janina Goletzke , Mirja Pagenkemper , Evelyn Huhn , Gudula Hansen , Felix Stahl , Petra Clara Arck , Anke Diemert

The placenta has a central function in fetal glucose supply and placental volume has received rising awareness as a potential predicting factor for adverse pregnancy outcomes. We aimed to examine whether placental volume is a prognostic marker for metabolic perturbations affecting both mother and child. Data from 100 women participating in a longitudinal cohort study of healthy pregnant women were obtained. Placental volume was assessed via transabdominal ultrasound at gestational weeks 12–14. Additional ultrasound measurements were conducted at gestational weeks 23–25, 28–30, and 34–36 to assess fetal anthropometry. HbA1c was measured in first trimester blood samples. Both cross-sectional and prospective associations between first trimester placental volume and selected fetal and maternal parameters were examined using multivariable linear regression models. Interactions by gender were observed for associations with HbA1c, anterior abdominal wall thickness (AAWT), gestational weight gain and estimated fetal weight. A higher first trimester placental volume was related to higher HbA1c levels in the first trimester, higher AAWT measures in the third trimester, and greater gestational weight gain in women carrying a male fetus only (all p = 0.02). In women carrying a female fetus, a positive association was observed between placental volume and estimated fetal weight at gestational week 34–36 (p = 0.045). None of the other maternal or fetal parameters were related to placental volume (p ≥ 0.1). Our results indicate first trimester placental volume to be a potential prognostic factor for maternal glucose metabolism and both fetal and maternal anthropometric perturbations particularly for those mothers carrying a male fetus.

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引用次数: 0

Immunoglobulin therapy for infertility and the role of immune cells in pregnancy success: An extensive investigation and update

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-02-14 DOI: 10.1016/j.jri.2025.104458

Lida Aslanian-kalkhoran , Narjes Nouri , Mohammad Sadegh Soltani-Zangbar , Amirhossein Mardi , leili Aghebati-Maleki

In the United States, roughly one out of every eight couples, or 7.5 million women, experience challenges related to conceiving or maintaining a pregnancy. The body's immune response is vital during pregnancy. T cells, natural killer (NK) cells, B cells, and macrophages (MQ) are immune cells in the female reproductive tract. They are in charge of maintaining tissue homeostasis and regulating the immune system's response to invasive pathogens. Failure to regulate these immune cells might result in inflammation, which reduces fertility. The immune system modulation of pregnancy loss has been studied with intralipid, intravenous immunoglobulin (IVIG), and paternal leukocyte vaccination. A concentrated antibody called intravenous immunoglobulin (IVIG) is utilized as a biological agent to treat autoimmune, viral, and inflammatory diseases and some immunodeficiencies. The main objective of this treatment is to restore a damaged immune system. IgGs, through binding to specific antigens, promote the innate immunity's cellular and humoral immune response by activating complements and binding to Fc receptors of several immune cells. Contrariwise, IVIG regulates pathogenic autoimmunity in animal models, including skin-blister diseases, nephrotoxic nephritis, and K/BxN arthritis. IVIG has, therefore, been of great interest as an immune modulator in several immune disorders. This review aims to investigate the immunological reasons of reproductive failure, focusing on the immunomodulatory effects of IVIG in its treatment.

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引用次数: 0

Sexual and reproductive health in overweight and obesity: Aims and visions for integrated research approaches

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-02-13 DOI: 10.1016/j.jri.2025.104454

Marie Albrecht , Nina Reitis , Mirja Pagenkemper , Ann-Christin Tallarek , Laura Pietras , Thula Koops , Dimitra E. Zazara , Anastasios D. Giannou , Mariana G. Garcia

Overweight and obesity increasingly affect women in their reproductive phase, during family planning, pregnancy, breastfeeding and the postpartum period. Overweight and obesity are associated with impaired sexual and reproductive health, including increased rates of infertility, pregnancy complications, and reduced breastfeeding rates. Furthermore, maternal overweight and obesity are associated with long-term negative health consequences for the child, such as an increased risk for respiratory and metabolic disease. With the Junior Research Center for Reproduction: Sexual and Reproductive Health in Overweight and Obesity (SRHOO Center), we aim to address the effects of overweight and obesity on sexual and reproductive health in an interdisciplinary approach, combining the areas of obstetrics and midwifery, sexual health research, basic research in feto-maternal medicine and glycoimmunology, pediatrics, as well as endocrinology, metabolism and bariatric surgery. Combining these areas of expertise, we seek (1) to understand the effects of overweight and obesity on sexual and reproductive health in different patient groups, focusing on their specific needs in order to provide appropriate counselling and access to healthcare; (2) to improve reproductive health in different groups of overweight and obese patients; and (3) to create interdisciplinary, comprehensive scientific and clinical training regarding sexual and reproductive health in overweight and obese patients. In this short introduction to the SRHOO Center, we provide information on its structure, aims and individual projects as well as its presumed long-term implications for clinical care and public health.

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引用次数: 0