Journal of Reproductive Immunology最新文献_第8页

Impact of lymphocyte immunotherapy (LIT) on fertility rates in recurrent pregnancy loss (RPL) women with antinuclear antibodies: A randomized clinical trial

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-01-15 DOI: 10.1016/j.jri.2025.104432

Mohsen Dashti , Amin Kamrani , Zahra Shahir-Khajeh , Javad Ahmadian Heris , Leili Aghebati-Maleki , Shahla Danaii , Forough Chakari-Khiavi , Behnam Shahriar , Mehrin Sadough , Sina Baharaghdam , Elham Badihi , Amir Mehdizadeh , Mehdi Yousefi

To further evaluate the effects of lymphocyte immunotherapy (LIT) for the treatment of RPL patients this study aimed to utilize this type of treatment in RPL patients with positive antinuclear antibodies (ANA) in comparison to ANA-negative RPL women. To this aim, 84 ANA-positive, 114 ANA negative, and 50 healthy pregnant women were recruited. To examine the frequency of cells before and after LIT, flowcytometry technique was employed. The levels of cytokines gene expression were also measured using real-time PCR. The ELISA technique was employed to assess the level of secreted cytokines in serum. Initial evaluation before LIT showed significantly lower NK cells and Th1/Th2 ratio in healthy pregnant women compared to both ANA-negative, and positive patients. Moreover, healthy pregnant women had significantly lower pro-inflammatory cytokine (IFN-γ) and higher anti-inflammatory cytokines (TGF-β and IL-4) compared to RPL patients. After LIT, NK cells frequency significantly decreased in both ANA-negative and -positive groups, however, reduced Th1/Th2 ratio was only significant in ANA-negative group. Significantly increased and decreased IL-4 and IFN-γ were only observed in ANA-negative patients. Furthermore, patients receiving routine treatment did not experience any remarkable changes in terms of cell frequency and cytokine levels. This study showed a significant improvement in pregnancy outcomes including increased pregnancy rate and live birth, and decreased miscarriages in both ANA-negative and positive RPL patients, which were notably higher in ANA-negative group.

{"title":"Impact of lymphocyte immunotherapy (LIT) on fertility rates in recurrent pregnancy loss (RPL) women with antinuclear antibodies: A randomized clinical trial","authors":"Mohsen Dashti , Amin Kamrani , Zahra Shahir-Khajeh , Javad Ahmadian Heris , Leili Aghebati-Maleki , Shahla Danaii , Forough Chakari-Khiavi , Behnam Shahriar , Mehrin Sadough , Sina Baharaghdam , Elham Badihi , Amir Mehdizadeh , Mehdi Yousefi","doi":"10.1016/j.jri.2025.104432","DOIUrl":"10.1016/j.jri.2025.104432","url":null,"abstract":"<div><div>To further evaluate the effects of lymphocyte immunotherapy (LIT) for the treatment of RPL patients this study aimed to utilize this type of treatment in RPL patients with positive antinuclear antibodies (ANA) in comparison to ANA-negative RPL women. To this aim, 84 ANA-positive, 114 ANA negative, and 50 healthy pregnant women were recruited. To examine the frequency of cells before and after LIT, flowcytometry technique was employed. The levels of cytokines gene expression were also measured using real-time PCR. The ELISA technique was employed to assess the level of secreted cytokines in serum. Initial evaluation before LIT showed significantly lower NK cells and Th1/Th2 ratio in healthy pregnant women compared to both ANA-negative, and positive patients. Moreover, healthy pregnant women had significantly lower pro-inflammatory cytokine (IFN-γ) and higher anti-inflammatory cytokines (TGF-β and IL-4) compared to RPL patients. After LIT, NK cells frequency significantly decreased in both ANA-negative and -positive groups, however, reduced Th1/Th2 ratio was only significant in ANA-negative group. Significantly increased and decreased IL-4 and IFN-γ were only observed in ANA-negative patients. Furthermore, patients receiving routine treatment did not experience any remarkable changes in terms of cell frequency and cytokine levels. This study showed a significant improvement in pregnancy outcomes including increased pregnancy rate and live birth, and decreased miscarriages in both ANA-negative and positive RPL patients, which were notably higher in ANA-negative group.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"168 ","pages":"Article 104432"},"PeriodicalIF":2.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023781","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

Causal relationships between immune cells, inflammatory factors, and preeclampsia: A two-step, two-sample mendelian randomization study

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-01-15 DOI: 10.1016/j.jri.2025.104428

Yuxiu Wang , Shijun Ni , Feng Liu , Lining Guo , Cha Han

Background

Preeclampsia (PE) is a complex hypertensive disorder that occurs during pregnancy, with the immune system playing a key role. Although immune modulation is implicated in PE progression, the roles of specific immune cells and inflammatory mediators remain unclear.

Methods

We conducted a two-sample, two-step Mendelian randomization (MR) analysis, primarily using the inverse-variance weighted method, to investigate the causal effect of immune cell traits on PE. Additionally, we assessed the potential mediation effects of inflammatory factors.

Results

The MR analyses revealed that 22 immune cell traits exert protective effects against PE, whereas 19 are associated with an increased risk. Additionally, four inflammatory factors were suggested to be linked to PE. Mediation analysis identified the absolute count (AC) of CD33 + HLA DR+ cells, including the CD14 − subset, as causally related to PE. Both the total effect of the CD33 + HLA DR+ AC (odds ratio [OR] = 0.977, 95 % confidence interval [CI], 0.960–0.994; P = 0.010) and the effect of CD33 + HLA DR+ CD14 − cells (OR = 0.977, 95 % CI, 0.963–0.991; P = 0.001) were significant. These effects were partially mediated by STAM-binding protein levels, contributing 16.7 % and 15.0 % to the total effects of the CD33 + HLA DR+ AC and CD33 + HLA DR+ CD14 − AC, respectively.

Conclusion

This study establishes a causal relationship between specific immune cells and PE, potentially mediated by inflammatory factors, highlighting the importance of these traits in PE pathogenesis. Further research is needed to validate these findings based on larger, more diverse cohorts.

{"title":"Causal relationships between immune cells, inflammatory factors, and preeclampsia: A two-step, two-sample mendelian randomization study","authors":"Yuxiu Wang , Shijun Ni , Feng Liu , Lining Guo , Cha Han","doi":"10.1016/j.jri.2025.104428","DOIUrl":"10.1016/j.jri.2025.104428","url":null,"abstract":"<div><h3>Background</h3><div>Preeclampsia (PE) is a complex hypertensive disorder that occurs during pregnancy, with the immune system playing a key role. Although immune modulation is implicated in PE progression, the roles of specific immune cells and inflammatory mediators remain unclear.</div></div><div><h3>Methods</h3><div>We conducted a two-sample, two-step Mendelian randomization (MR) analysis, primarily using the inverse-variance weighted method, to investigate the causal effect of immune cell traits on PE. Additionally, we assessed the potential mediation effects of inflammatory factors.</div></div><div><h3>Results</h3><div>The MR analyses revealed that 22 immune cell traits exert protective effects against PE, whereas 19 are associated with an increased risk. Additionally, four inflammatory factors were suggested to be linked to PE. Mediation analysis identified the absolute count (AC) of CD33 + HLA DR+ cells, including the CD14 − subset, as causally related to PE. Both the total effect of the CD33 + HLA DR+ AC (odds ratio [OR] = 0.977, 95 % confidence interval [CI], 0.960–0.994; P = 0.010) and the effect of CD33 + HLA DR+ CD14 − cells (OR = 0.977, 95 % CI, 0.963–0.991; P = 0.001) were significant. These effects were partially mediated by STAM-binding protein levels, contributing 16.7 % and 15.0 % to the total effects of the CD33 + HLA DR+ AC and CD33 + HLA DR+ CD14 − AC, respectively.</div></div><div><h3>Conclusion</h3><div>This study establishes a causal relationship between specific immune cells and PE, potentially mediated by inflammatory factors, highlighting the importance of these traits in PE pathogenesis. Further research is needed to validate these findings based on larger, more diverse cohorts.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"168 ","pages":"Article 104428"},"PeriodicalIF":2.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047175","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

Impact of low-dose aspirin therapy initiation timing on pregnancy outcomes after frozen-thawed blastocyst transfer 低剂量阿司匹林起始时间对冻融囊胚移植后妊娠结局的影响。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-01-13 DOI: 10.1016/j.jri.2025.104430

Keiji Kuroda , Azusa Moriyama , Ryo Tsutsumi , Rutsuko Hobo , Hiroshi Motoyama , Yasushi Kuribayashi , Shuko Nojiri , Tetsuo Maruyama , Rikikazu Sugiyama

Clinical effects of low-dose aspirin (LDA) on embryo implantation still remains controversial; therefore, we investigated the appropriate timing for starting LDA in frozen-thawed embryo transfer (ET) cycles. A cross-sectional study was conducted on 885 infertile women who underwent thrombophilia screening between 2020 and 2023. We recruited first frozen-thawed blastocyst transfer cycles in 553 consecutive women aged < 40 years. LDA was started on the day of ET from 2020 to 2021 in 79 women (day 0 group) and at 5 days after ET from 2021 to 2023 in 215 women (day 5 group). We also recruited 259 consecutive women who underwent first frozen-thawed blastocyst transfer without LDA treatment from 2020 to 2023 (control). We compared pregnancy outcomes after frozen-thawed ET between the three groups. In results, clinical pregnancy and livebirth rates after frozen-thawed ET in the day 0 group were significantly lower than those in the other two groups (clinical pregnancy rates: 57.5 %, 40.5 %, and 61.4 %, p = 0.005 and livebirth rates: 48.6 %, 34.2 %, and 54.0 %, p = 0.01 in the control, day 0, and day 5 groups, respectively). Multivariable logistic regression analysis showed that livebirth rate in the day 0 group was significantly lower than those in the other groups (odds ratio [OR]: 0.54, 95 % confidential interval [CI]: 0.31 −0.95); however, no significant difference in livebirth rates was found between the day 5 and control groups (OR: 1.13, 95 %CI: 0.70 −1.80). Starting LDA prior to implantation may decrease pregnancy and livebirth rates after frozen-thawed blastocyst transfer.

低剂量阿司匹林（LDA）对胚胎植入的临床效果仍存在争议；因此，我们研究了在冻融胚胎移植（ET）周期中启动LDA的合适时机。一项横断面研究对885名在2020年至2023年间接受血栓性疾病筛查的不孕妇女进行了研究。我们在553名连续的年龄女性中招募了第一个冷冻解冻囊胚移植周期

{"title":"Impact of low-dose aspirin therapy initiation timing on pregnancy outcomes after frozen-thawed blastocyst transfer","authors":"Keiji Kuroda , Azusa Moriyama , Ryo Tsutsumi , Rutsuko Hobo , Hiroshi Motoyama , Yasushi Kuribayashi , Shuko Nojiri , Tetsuo Maruyama , Rikikazu Sugiyama","doi":"10.1016/j.jri.2025.104430","DOIUrl":"10.1016/j.jri.2025.104430","url":null,"abstract":"<div><div>Clinical effects of low-dose aspirin (LDA) on embryo implantation still remains controversial; therefore, we investigated the appropriate timing for starting LDA in frozen-thawed embryo transfer (ET) cycles. A cross-sectional study was conducted on 885 infertile women who underwent thrombophilia screening between 2020 and 2023. We recruited first frozen-thawed blastocyst transfer cycles in 553 consecutive women aged < 40 years. LDA was started on the day of ET from 2020 to 2021 in 79 women (day 0 group) and at 5 days after ET from 2021 to 2023 in 215 women (day 5 group). We also recruited 259 consecutive women who underwent first frozen-thawed blastocyst transfer without LDA treatment from 2020 to 2023 (control). We compared pregnancy outcomes after frozen-thawed ET between the three groups. In results, clinical pregnancy and livebirth rates after frozen-thawed ET in the day 0 group were significantly lower than those in the other two groups (clinical pregnancy rates: 57.5 %, 40.5 %, and 61.4 %, p = 0.005 and livebirth rates: 48.6 %, 34.2 %, and 54.0 %, p = 0.01 in the control, day 0, and day 5 groups, respectively). Multivariable logistic regression analysis showed that livebirth rate in the day 0 group was significantly lower than those in the other groups (odds ratio [OR]: 0.54, 95 % confidential interval [CI]: 0.31 −0.95); however, no significant difference in livebirth rates was found between the day 5 and control groups (OR: 1.13, 95 %CI: 0.70 −1.80). Starting LDA prior to implantation may decrease pregnancy and livebirth rates after frozen-thawed blastocyst transfer.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"168 ","pages":"Article 104430"},"PeriodicalIF":2.9,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007357","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 connection between endometriosis and secondary dysmenorrhea 子宫内膜异位症与继发性痛经的关系。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-01-09 DOI: 10.1016/j.jri.2025.104425

Ismat Ara Begum

Endometriosis (EMS) is a prevalent gynecological condition characterized by the presence of endometrial tissue outside the uterus, often leading to secondary dysmenorrhea (SD), chronic pelvic pain and infertility. This review explores the intricate connection between EMS- associated pain and SD, focusing on the pathophysiological mechanisms underlying dysmenorrhea in EMS. Key contributors to pain include inflammation, aberrant immune responses, neurogenic inflammation, peritoneal irritation, peripheral sensitization, central sensitization and cross-organ sensitization. Understanding the pain pathways in EMS highlights the complexity of symptom manifestation and underscores the necessity for a multidisciplinary approach to management. Clinical manifestations, including chronic pelvic pain, dyspareunia, infertility, gastrointestinal and bladder symptoms, fatigue and malaise, are discussed, emphasizing the diverse impact of EMS on women’s health. Various treatment modalities, ranging from pharmacological interventions to surgical and complementary approaches, are outlined to provide comprehensive management strategies for EMS-related menstrual pain/SD. This review aims to enhance understanding and facilitate the effective management of EMS-associated SD, ultimately improving the quality of life for affected individuals.

子宫内膜异位症（EMS）是一种常见的妇科疾病，其特征是子宫外存在子宫内膜组织，常导致继发性痛经（SD）、慢性盆腔疼痛和不孕。这篇综述探讨了EMS相关疼痛和SD之间的复杂联系，重点讨论了EMS中痛经的病理生理机制。引起疼痛的主要因素包括炎症、异常免疫反应、神经源性炎症、腹膜刺激、外周致敏、中枢致敏和跨器官致敏。了解EMS中的疼痛通路强调了症状表现的复杂性，并强调了多学科方法管理的必要性。临床表现，包括慢性盆腔疼痛，性交困难，不孕症，胃肠道和膀胱症状，疲劳和不适，讨论，强调EMS对女性健康的不同影响。各种治疗方式，从药物干预到手术和辅助方法，概述了ems相关的经期疼痛/SD的综合管理策略。本综述旨在增进对ems相关的SD的理解和有效管理，最终改善受影响个体的生活质量。

{"title":"The connection between endometriosis and secondary dysmenorrhea","authors":"Ismat Ara Begum","doi":"10.1016/j.jri.2025.104425","DOIUrl":"10.1016/j.jri.2025.104425","url":null,"abstract":"<div><div>Endometriosis (EMS) is a prevalent gynecological condition characterized by the presence of endometrial tissue outside the uterus, often leading to secondary dysmenorrhea (SD), chronic pelvic pain and infertility. This review explores the intricate connection between EMS- associated pain and SD, focusing on the pathophysiological mechanisms underlying dysmenorrhea in EMS. Key contributors to pain include inflammation, aberrant immune responses, neurogenic inflammation, peritoneal irritation, peripheral sensitization, central sensitization and cross-organ sensitization. Understanding the pain pathways in EMS highlights the complexity of symptom manifestation and underscores the necessity for a multidisciplinary approach to management. Clinical manifestations, including chronic pelvic pain, dyspareunia, infertility, gastrointestinal and bladder symptoms, fatigue and malaise, are discussed, emphasizing the diverse impact of EMS on women’s health. Various treatment modalities, ranging from pharmacological interventions to surgical and complementary approaches, are outlined to provide comprehensive management strategies for EMS-related menstrual pain/SD. This review aims to enhance understanding and facilitate the effective management of EMS-associated SD, ultimately improving the quality of life for affected individuals.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"168 ","pages":"Article 104425"},"PeriodicalIF":2.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007359","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

Economic impact of resignation due to miscarriage: A survey of patients with recurrent pregnancy loss and pregnant women in Japan 因流产而辞职的经济影响：日本反复流产患者和孕妇的调查。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-01-09 DOI: 10.1016/j.jri.2025.104424

Chihiro Banno , Mayumi Sugiura-Ogasawara , Shinobu Goto , Takeshi Sato , Naomi Nishikawa , Kiwamu Ando , Yoko Morita

Sporadic early miscarriages occur primarily due to embryonic aneuploidy. There is no evidence showing that stress is a direct cause of miscarriage. Yet, despite this, a national US survey and a Japanese survey found that many people mistakenly attributed miscarriage to the mental state or behavior of the women. Our present survey examined the risk factors and economic impact of resignation associated with miscarriage and pregnancy in Japan.

The questionnaire to be completed consisted of 17 questions concerning individual characteristics and resignation from the workforce.

Of the 1177 women, 392 left their employment and 785 continued working. At least 9 % of the women left their jobs because of miscarriage. The economic loss because of resignation due to miscarriage was found to be JPY 46,666,959,300 per year (USD 303,032,203). The number of children, exposure to in vitro fertilization and living with or near their father-in-law were independent risk factors for resignation. Significantly more women who left work in the first pregnancy due to miscarriage and infertility treatment remained unemployed. Thoughts that led to the conclusion that it is better to avoid working during pregnancy, that it is better not to do any work that places a heavy burden on the body, or that it is better not to work long or irregular hours during pregnancy were also independent risk factors for resignation. Significantly more women who lived with or near their mothers remained employed. Reproductive education is needed to prevent resignation following a miscarriage or during a pregnancy.

零星的早期流产主要是由于胚胎非整倍体。没有证据表明压力是流产的直接原因。然而，尽管如此，美国的一项全国性调查和日本的一项调查发现，许多人错误地将流产归咎于女性的精神状态或行为。我们目前的调查研究了日本流产和怀孕相关辞职的风险因素和经济影响。要完成的问卷包括17个问题，涉及个人特征和辞职。在1177名女性中，392人离职，785人继续工作。至少有9 %的女性因为流产而离职。因流产而辞职的经济损失为每年46,666,959,300日元（303,032,203美元）。子女数量、接触体外受精、与公公同住或住在公公附近是辞职的独立危险因素。由于流产和不孕症治疗而在第一次怀孕时离开工作岗位的妇女明显更多地失业。在怀孕期间最好避免工作，最好不要做任何给身体带来沉重负担的工作，或者在怀孕期间最好不要长时间或不规律地工作的想法也是辞职的独立危险因素。与母亲住在一起或住在母亲附近的女性中，有更多的人仍然有工作。需要进行生殖教育，以防止流产后或怀孕期间辞职。

{"title":"Economic impact of resignation due to miscarriage: A survey of patients with recurrent pregnancy loss and pregnant women in Japan","authors":"Chihiro Banno , Mayumi Sugiura-Ogasawara , Shinobu Goto , Takeshi Sato , Naomi Nishikawa , Kiwamu Ando , Yoko Morita","doi":"10.1016/j.jri.2025.104424","DOIUrl":"10.1016/j.jri.2025.104424","url":null,"abstract":"<div><div>Sporadic early miscarriages occur primarily due to embryonic aneuploidy. There is no evidence showing that stress is a direct cause of miscarriage. Yet, despite this, a national US survey and a Japanese survey found that many people mistakenly attributed miscarriage to the mental state or behavior of the women. Our present survey examined the risk factors and economic impact of resignation associated with miscarriage and pregnancy in Japan.</div><div>The questionnaire to be completed consisted of 17 questions concerning individual characteristics and resignation from the workforce.</div><div>Of the 1177 women, 392 left their employment and 785 continued working. At least 9 % of the women left their jobs because of miscarriage. The economic loss because of resignation due to miscarriage was found to be JPY 46,666,959,300 per year (USD 303,032,203). The number of children, exposure to in vitro fertilization and living with or near their father-in-law were independent risk factors for resignation. Significantly more women who left work in the first pregnancy due to miscarriage and infertility treatment remained unemployed. Thoughts that led to the conclusion that it is better to avoid working during pregnancy, that it is better not to do any work that places a heavy burden on the body, or that it is better not to work long or irregular hours during pregnancy were also independent risk factors for resignation. Significantly more women who lived with or near their mothers remained employed. Reproductive education is needed to prevent resignation following a miscarriage or during a pregnancy.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"168 ","pages":"Article 104424"},"PeriodicalIF":2.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007257","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

Reduced expression of programmed cell death protein 1 on peripheral regulatory B cells in pre-eclampsia – Signs of impaired immune suppression 子痫前期外周调节性B细胞程序性细胞死亡蛋白1的表达减少-免疫抑制受损的迹象

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-01-09 DOI: 10.1016/j.jri.2025.104426

Sophie Brondt Salby , Gry Persson , Nanna Heldager Pedersen , Gökmen Turan , Laura Kimmerslev , Katrine Folmann Finne , Iben Weisdorf , Morten Lebech , Thomas Vauvert F. Hviid

Immunological changes are believed to be a part of pre-eclampsia etiology. This study investigated the distribution of the specific peripheral B lymphocyte phenotypes in pre-eclampsia cases compared to uncomplicated pregnancies. The study cohort included 29 women with pre-eclampsia and 14 women with uncomplicated pregnancies. Blood samples were collected in the third trimester of primigravidae pregnancies, and immune cells were analyzed using flow cytometry. Cases with pre-eclampsia showed a significantly reduced expression of programmed cell death protein 1 (PD-1) on CD27⁺CD24^hiCD38^hi regulatory B cells compared with control pregnancies (p = 0.002; multivariate logistic regression: p = 0.009). Trends for a reduced PD-1 expression on regulatory CD27⁺CD24^hi B cells and on live CD19⁺ B cells were observed in cases of pre-eclampsia (p = 0.011 and p = 0.035; respectively). No significant differences between pre-eclampsia cases and controls in percentages of B cells, B1a cells, plasmablasts, naïve B cells, transitional/immature B cells, memory B cells, regulatory CD27⁺CD24^hi B cells and regulatory CD27⁺CD24^hiCD38^hi B cells were observed. This is the first study to report reduced PD-1 expression on live B cells and regulatory B cells in pre-eclampsia. These results are in line with previous studies of peripheral regulatory T cells and decidual lymphocytes from pre-eclampsia patients. Reduced PD-1 expression on regulatory B cells in pre-eclampsia could indicate that a lack of immune suppression might play a role in the pathophysiology of pre-eclampsia.

免疫变化被认为是子痫前期病因的一部分。本研究探讨了子痫前期病例与未并发症妊娠的特异性外周B淋巴细胞表型的分布。研究队列包括29名先兆子痫妇女和14名无并发症妊娠妇女。在初生蜂科妊娠晚期采集血样，用流式细胞术分析免疫细胞。与对照组妊娠相比，子痫前期患者CD27+CD24hiCD38hi调节性B细胞上程序性细胞死亡蛋白1 （PD-1）的表达显著降低(p = 0.002；多因素logistic回归：p = 0.009)。在子痫前期患者中，PD-1在调节性CD27+CD24hi B细胞和活CD19+ B细胞上的表达降低(p = 0.011和p = 0.035；分别)。子痫前期患者B细胞、B1a细胞、浆母细胞、naïve B细胞、过渡/未成熟B细胞、记忆B细胞、调节性CD27+CD24hi B细胞和调节性CD27+CD24hiCD38hi B细胞的百分比与对照组无显著差异。这是首次报道子痫前期活B细胞和调节性B细胞中PD-1表达降低的研究。这些结果与先前对子痫前期患者外周血调节性T细胞和蜕膜淋巴细胞的研究一致。子痫前期调节性B细胞PD-1表达降低可能提示免疫抑制缺失可能在子痫前期病理生理中发挥作用。

{"title":"Reduced expression of programmed cell death protein 1 on peripheral regulatory B cells in pre-eclampsia – Signs of impaired immune suppression","authors":"Sophie Brondt Salby , Gry Persson , Nanna Heldager Pedersen , Gökmen Turan , Laura Kimmerslev , Katrine Folmann Finne , Iben Weisdorf , Morten Lebech , Thomas Vauvert F. Hviid","doi":"10.1016/j.jri.2025.104426","DOIUrl":"10.1016/j.jri.2025.104426","url":null,"abstract":"<div><div>Immunological changes are believed to be a part of pre-eclampsia etiology. This study investigated the distribution of the specific peripheral B lymphocyte phenotypes in pre-eclampsia cases compared to uncomplicated pregnancies. The study cohort included 29 women with pre-eclampsia and 14 women with uncomplicated pregnancies. Blood samples were collected in the third trimester of primigravidae pregnancies, and immune cells were analyzed using flow cytometry. Cases with pre-eclampsia showed a significantly reduced expression of programmed cell death protein 1 (PD-1) on CD27<sup>+</sup>CD24<sup>hi</sup>CD38<sup>hi</sup> regulatory B cells compared with control pregnancies (p = 0.002; multivariate logistic regression: p = 0.009). Trends for a reduced PD-1 expression on regulatory CD27<sup>+</sup>CD24<sup>hi</sup> B cells and on live CD19<sup>+</sup> B cells were observed in cases of pre-eclampsia (p = 0.011 and p = 0.035; respectively). No significant differences between pre-eclampsia cases and controls in percentages of B cells, B1a cells, plasmablasts, naïve B cells, transitional/immature B cells, memory B cells, regulatory CD27<sup>+</sup>CD24<sup>hi</sup> B cells and regulatory CD27<sup>+</sup>CD24<sup>hi</sup>CD38<sup>hi</sup> B cells were observed. This is the first study to report reduced PD-1 expression on live B cells and regulatory B cells in pre-eclampsia. These results are in line with previous studies of peripheral regulatory T cells and decidual lymphocytes from pre-eclampsia patients. Reduced PD-1 expression on regulatory B cells in pre-eclampsia could indicate that a lack of immune suppression might play a role in the pathophysiology of pre-eclampsia.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"168 ","pages":"Article 104426"},"PeriodicalIF":2.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007358","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

Mechanisms underlying changes in intestinal permeability during pregnancy and their implications for maternal and infant health 妊娠期间肠道通透性变化的机制及其对母婴健康的影响。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-01-07 DOI: 10.1016/j.jri.2025.104423

Guangyu Ma , Zhongsheng Chen , Zhuojun Xie , JinXiang Liu , Xiaomin Xiao

Proper regulation of intestinal permeability is essential for maintaining the integrity of the intestinal mucosal barrier. An abnormal increase in permeability can significantly contribute to the onset and progression of various diseases, including autoimmune disorders, metabolic conditions, allergies, and inflammatory bowel diseases. The potential connection between intestinal permeability and maternal health during pregnancy is increasingly recognized, yet a comprehensive review remains lacking. Pregnancy triggers a series of physiological structural adaptations and significant hormonal fluctuations that collectively contribute to an increase in intestinal permeability. Although an increase in intestinal permeability is typically a normal physiological response during pregnancy, an abnormal rise is associated with immune dysregulation, metabolic disorders, and various pregnancy-related complications, such as recurrent pregnancy loss, gestational diabetes mellitus, overweight and obesity during pregnancy, intrahepatic cholestasis of pregnancy, and preeclampsia. This paper discusses the components of the intestinal mucosal barrier, the concept of intestinal permeability and its measurement methods, and the mechanisms and physiological significance of increased intestinal permeability during pregnancy. It thoroughly explores the association between abnormal intestinal permeability during pregnancy and maternal diseases, aiming to provide evidence for the pathophysiology of disease development in pregnant women. Additionally, the paper examines intervention methods, such as gut microbiota modulation and nutritional interventions, to regulate intestinal permeability during pregnancy, improve immune and metabolic states, and offer feasible strategies for the prevention and adjuvant treatment of clinical pregnancy complications.

适当调节肠通透性对维持肠黏膜屏障的完整性至关重要。通透性异常增加可显著促进各种疾病的发生和进展，包括自身免疫性疾病、代谢疾病、过敏和炎症性肠病。肠道通透性与妊娠期孕产妇健康之间的潜在联系越来越被认识到，但仍缺乏全面的审查。怀孕触发一系列生理结构适应和显著的激素波动，共同促进肠道通透性增加。虽然肠通透性增加是妊娠期典型的正常生理反应，但异常升高与免疫失调、代谢紊乱和各种妊娠相关并发症相关，如复发性妊娠丢失、妊娠期糖尿病、妊娠期超重和肥胖、妊娠期肝内胆汁淤积和先兆子痫。本文讨论了肠粘膜屏障的组成、肠通透性的概念和测量方法，以及妊娠期肠通透性增加的机制和生理意义。深入探讨妊娠期肠道通透性异常与孕产妇疾病的关系，旨在为孕妇疾病发展的病理生理学提供依据。此外，本文还探讨了通过调节肠道菌群和营养干预等干预方法，调节妊娠期肠道通透性，改善免疫和代谢状态，为临床妊娠并发症的预防和辅助治疗提供可行的策略。

{"title":"Mechanisms underlying changes in intestinal permeability during pregnancy and their implications for maternal and infant health","authors":"Guangyu Ma , Zhongsheng Chen , Zhuojun Xie , JinXiang Liu , Xiaomin Xiao","doi":"10.1016/j.jri.2025.104423","DOIUrl":"10.1016/j.jri.2025.104423","url":null,"abstract":"<div><div>Proper regulation of intestinal permeability is essential for maintaining the integrity of the intestinal mucosal barrier. An abnormal increase in permeability can significantly contribute to the onset and progression of various diseases, including autoimmune disorders, metabolic conditions, allergies, and inflammatory bowel diseases. The potential connection between intestinal permeability and maternal health during pregnancy is increasingly recognized, yet a comprehensive review remains lacking. Pregnancy triggers a series of physiological structural adaptations and significant hormonal fluctuations that collectively contribute to an increase in intestinal permeability. Although an increase in intestinal permeability is typically a normal physiological response during pregnancy, an abnormal rise is associated with immune dysregulation, metabolic disorders, and various pregnancy-related complications, such as recurrent pregnancy loss, gestational diabetes mellitus, overweight and obesity during pregnancy, intrahepatic cholestasis of pregnancy, and preeclampsia. This paper discusses the components of the intestinal mucosal barrier, the concept of intestinal permeability and its measurement methods, and the mechanisms and physiological significance of increased intestinal permeability during pregnancy. It thoroughly explores the association between abnormal intestinal permeability during pregnancy and maternal diseases, aiming to provide evidence for the pathophysiology of disease development in pregnant women. Additionally, the paper examines intervention methods, such as gut microbiota modulation and nutritional interventions, to regulate intestinal permeability during pregnancy, improve immune and metabolic states, and offer feasible strategies for the prevention and adjuvant treatment of clinical pregnancy complications.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"168 ","pages":"Article 104423"},"PeriodicalIF":2.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142965501","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

Unraveling the uterine fluid proteome of mares diagnosed with post-breeding and infectious endometritis 诊断为生殖期和感染性子宫内膜炎的母马子宫液蛋白质组的研究

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2024-11-28 DOI: 10.1016/j.jri.2024.104401

Carlos Mattos Teixeira-Soares , Arabela Guedes Viana , Renner Philipe Rodrigues Carvalho , Edvaldo Barros , Camilo Ramirez-Lopez , Arlindo A. Moura , Mariana Machado-Neves

Endometritis is the leading cause of subfertility in mares and a significant challenge to equine reproduction. Unraveling uterine fluid proteome may promote advancements in the knowledge of endometritis etiopathogeneses and its diagnosis and therapeutic practices. Therefore, we aimed to characterize and compare the protein profile of the uterine fluid from healthy mares and animals diagnosed with endometritis. Mangalarga Marchador breed mares from Muriaé - Brazil were divided into control, infectious endometritis, and post-breeding endometritis groups (n = 8/ group). Uterine fluid was collected via low-volume lavage and subjected to protein identification and relative abundance counting. From the 549 proteins detected, 279 were in the uterine fluid of mares from the three experimental groups. Thirteen proteins expressed mostly in healthy mares were associated with endometrial remodeling and early embryonic development. Albumin and uteroglobin presented higher relative abundance in healthy mares and animals with infectious endometritis. Infectious endometritis exhibited proteins related to innate immune and inflammatory responses, including annexin and glutathione S-transferase, and the highest abundance of lipocalins. Fifty-five proteins detected in mares with post-breeding endometritis showed signaling pathways and biological processes related to the innate immune response. These animals also presented the highest abundance of PIGR proteins, which promote IgA transport from plasma into the endometrial mucosa. In conclusion, our results revealed distinct protein profiles from the uterine fluid of mares with infections and post-breeding endometritis. These findings provided valuable insights into the molecular alterations during the establishment and progression of endometritis, contributing to further identification of potential biomarkers.

子宫内膜炎是导致母马生育能力低下的主要原因，也是对马生殖的重大挑战。揭示子宫液蛋白质组可能促进子宫内膜炎发病机制及其诊断和治疗实践的进展。因此，我们旨在表征和比较健康母马和诊断为子宫内膜炎的动物子宫液的蛋白质谱。将巴西muria的Mangalarga Marchador种母马分为对照组、感染性子宫内膜炎组和种后子宫内膜炎组（n = 8/组）。通过小容量灌洗收集子宫液，进行蛋白鉴定和相对丰度计数。在检测到的549种蛋白质中，279种存在于三个实验组母马的子宫液中。在健康母马中主要表达的13种蛋白与子宫内膜重塑和早期胚胎发育有关。白蛋白和子宫红蛋白在感染性子宫内膜炎的健康母马和动物中呈现较高的相对丰度。感染性子宫内膜炎表现出与先天免疫和炎症反应相关的蛋白质，包括膜联蛋白和谷胱甘肽s -转移酶，以及最高丰度的脂钙蛋白。在育后子宫内膜炎母马中检测到55种蛋白质，显示了与先天免疫反应相关的信号通路和生物学过程。这些动物也表现出最高的PIGR蛋白丰度，促进IgA从血浆转运到子宫内膜粘膜。综上所述，我们的研究结果揭示了感染和繁殖后子宫内膜炎的母马子宫液中不同的蛋白质谱。这些发现为子宫内膜炎建立和发展过程中的分子改变提供了有价值的见解，有助于进一步确定潜在的生物标志物。

{"title":"Unraveling the uterine fluid proteome of mares diagnosed with post-breeding and infectious endometritis","authors":"Carlos Mattos Teixeira-Soares , Arabela Guedes Viana , Renner Philipe Rodrigues Carvalho , Edvaldo Barros , Camilo Ramirez-Lopez , Arlindo A. Moura , Mariana Machado-Neves","doi":"10.1016/j.jri.2024.104401","DOIUrl":"10.1016/j.jri.2024.104401","url":null,"abstract":"<div><div>Endometritis is the leading cause of subfertility in mares and a significant challenge to equine reproduction. Unraveling uterine fluid proteome may promote advancements in the knowledge of endometritis etiopathogeneses and its diagnosis and therapeutic practices. Therefore, we aimed to characterize and compare the protein profile of the uterine fluid from healthy mares and animals diagnosed with endometritis. Mangalarga Marchador breed mares from Muriaé - Brazil were divided into control, infectious endometritis, and post-breeding endometritis groups (<em>n</em> = 8/ group). Uterine fluid was collected via low-volume lavage and subjected to protein identification and relative abundance counting. From the 549 proteins detected, 279 were in the uterine fluid of mares from the three experimental groups. Thirteen proteins expressed mostly in healthy mares were associated with endometrial remodeling and early embryonic development. Albumin and uteroglobin presented higher relative abundance in healthy mares and animals with infectious endometritis. Infectious endometritis exhibited proteins related to innate immune and inflammatory responses, including annexin and glutathione S-transferase, and the highest abundance of lipocalins. Fifty-five proteins detected in mares with post-breeding endometritis showed signaling pathways and biological processes related to the innate immune response. These animals also presented the highest abundance of PIGR proteins, which promote IgA transport from plasma into the endometrial mucosa. In conclusion, our results revealed distinct protein profiles from the uterine fluid of mares with infections and post-breeding endometritis. These findings provided valuable insights into the molecular alterations during the establishment and progression of endometritis, contributing to further identification of potential biomarkers.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"167 ","pages":"Article 104401"},"PeriodicalIF":2.9,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743994","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

Expression of the mucin-like glycoprotein CD24 and its ligand siglec-10 in placentas with acute and post SARS-CoV-2 infection 黏液样糖蛋白CD24及其配体siglece -10在急性和后SARS-CoV-2感染胎盘中的表达

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2024-11-27 DOI: 10.1016/j.jri.2024.104400

Marina C. Seefried , Johanna Mittelberger , Manuela Franitza , Fabian Garrido , Carl Mathis Wild , Nina Ditsch , Oleksii Protsepko , Christina Kuhn , Christian Dannecker , Udo Jeschke , Hans-Peter Altevogt , Marei Sammar

CD24 is a mucin-like glycoprotein expressed on trophoblast cells and endothelial tissue of first and third trimester placentas. As an immune suppressor, CD24 may contribute to maternal immune tolerance to the growing fetus. CD24 is known to interact with the sialic acid-binding immunoglobulin-type lectins (Siglecs), specifically siglec-10. The aim of this study was to investigate the expression of both, CD24 and siglec-10 on placental tissue slides from acute covid patients, patients who survived a covid-19 infection and normal term controls. For the evaluation of CD24 & siglec-10 we used a total of 60 placentas, 10 acute covid-19 female, 10 acute covid-19 male, 10 post-covid-19 female, 10 post-covid-19 male, 10 female term controls and 10 male term controls. Immunohistochemical staining against CD24 and siglec-10 was performed and the expression of both markers was done with an immunoreactive score (IRS). Identity of CD24- or siglec-10 expressing cells was analyzed by double immune fluorescence analyses. The expression of CD24 is significantly downregulated on the extravillous trophoblast and on Hofbauer cells of female acute covid placentas. In the contrary, CD24 is significantly upregulated on male post-covid-19 Hofbauer cells. The CD24-ligand siglec-10 is significantly downregulated in post-covid-19 Hofbauer cells independently of fetal sex, whereas it shows significant higher expression in control female Hofbauer cells. CD24 and its ligand siglec-10 are differentially expressed in placentas of patients who survived a covid-19 infection. Surprisingly this effect is related to the fetal gender. Further investigation is necessary to analyze especially the imprinting effect of this infection.

CD24是一种黏液样糖蛋白，在妊娠早期和晚期胎盘的滋养细胞和内皮组织中表达。作为一种免疫抑制因子，CD24可能有助于母体对生长中的胎儿的免疫耐受。已知CD24与唾液酸结合免疫球蛋白型凝集素（Siglecs）相互作用，特别是Siglecs -10。本研究的目的是研究CD24和siglece -10在急性covid-19患者、covid-19感染幸存者和正常足月对照组胎盘组织载玻片上的表达。用于CD24的评价；siglece -10共使用60个胎盘，10个急性COVID-19女性，10个急性COVID-19男性，10个COVID-19后女性，10个COVID-19后男性，10个女性足月对照组和10个男性足月对照组。对CD24和siglec-10进行免疫组化染色，并用免疫反应评分（IRS）进行两种标记物的表达。双免疫荧光法分析CD24或siglece -10表达细胞的身份。CD24在急性胎盘上皮外滋养细胞和霍夫鲍尔细胞上的表达显著下调。相反，CD24在男性covid-19后霍夫鲍尔细胞中显著上调。cd24配体siglec-10在新冠病毒感染后的Hofbauer细胞中显著下调，与胎儿性别无关，而在对照雌性Hofbauer细胞中表达显著升高。CD24及其配体siglece -10在covid-19感染存活患者的胎盘中差异表达。令人惊讶的是，这种影响与胎儿性别有关。特别是对这种感染的印记效应，需要进一步的调查分析。

{"title":"Expression of the mucin-like glycoprotein CD24 and its ligand siglec-10 in placentas with acute and post SARS-CoV-2 infection","authors":"Marina C. Seefried , Johanna Mittelberger , Manuela Franitza , Fabian Garrido , Carl Mathis Wild , Nina Ditsch , Oleksii Protsepko , Christina Kuhn , Christian Dannecker , Udo Jeschke , Hans-Peter Altevogt , Marei Sammar","doi":"10.1016/j.jri.2024.104400","DOIUrl":"10.1016/j.jri.2024.104400","url":null,"abstract":"<div><div>CD24 is a mucin-like glycoprotein expressed on trophoblast cells and endothelial tissue of first and third trimester placentas. As an immune suppressor, CD24 may contribute to maternal immune tolerance to the growing fetus. CD24 is known to interact with the sialic acid-binding immunoglobulin-type lectins (Siglecs), specifically siglec-10. The aim of this study was to investigate the expression of both, CD24 and siglec-10 on placental tissue slides from acute covid patients, patients who survived a covid-19 infection and normal term controls. For the evaluation of CD24 & siglec-10 we used a total of 60 placentas, 10 acute covid-19 female, 10 acute covid-19 male, 10 post-covid-19 female, 10 post-covid-19 male, 10 female term controls and 10 male term controls. Immunohistochemical staining against CD24 and siglec-10 was performed and the expression of both markers was done with an immunoreactive score (IRS). Identity of CD24- or siglec-10 expressing cells was analyzed by double immune fluorescence analyses. The expression of CD24 is significantly downregulated on the extravillous trophoblast and on Hofbauer cells of female acute covid placentas. In the contrary, CD24 is significantly upregulated on male post-covid-19 Hofbauer cells. The CD24-ligand siglec-10 is significantly downregulated in post-covid-19 Hofbauer cells independently of fetal sex, whereas it shows significant higher expression in control female Hofbauer cells. CD24 and its ligand siglec-10 are differentially expressed in placentas of patients who survived a covid-19 infection. Surprisingly this effect is related to the fetal gender. Further investigation is necessary to analyze especially the imprinting effect of this infection.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"167 ","pages":"Article 104400"},"PeriodicalIF":2.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142744015","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

Metabonomics analysis of decidual tissue in patients with recurrent spontaneous abortion 复发性自然流产患者蜕膜组织的代谢组学分析

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2024-11-20 DOI: 10.1016/j.jri.2024.104398

Zhihui Chen , Huifang Yin , Youmei Long , Huiling Zhu , Renmei Xiong , Xin Duan , Hongyu Liu , Jiada Li

Objective

This study aimed to delineate the metabolic differences and identify enriched pathways in the decidual tissue of patients with recurrent spontaneous abortion (RSA) compared to normal pregnant women.

Methods

A cohort of 25 RSA patients and 25 normal pregnant women was recruited for the study. Non-targeted metabolomic analysis of decidual tissue was conducted using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS). Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were employed to identify differential metabolites. Pathway enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to elucidate associated metabolic pathways. Quantitative polymerase chain reaction (qPCR) was utilized to assess the expression levels of key proteins related to these pathways, including acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), and indoleamine 2,3-dioxygenase (IDO).

Results

A total of 54 metabolites were identified with significant differences between the decidual tissues of RSA patients and normal controls, corresponding to 29 significantly enriched metabolic pathways (P<0.05). The expression of ACSL4 was markedly upregulated, while the expression of GPX4 and IDO were significantly downregulated in RSA patients (P<0.05).

Conclusions

This study elucidates substantial metabolic disruptions in the decidual tissue of RSA patients, identifying 54 differential metabolites and 29 enriched pathways. The altered expression of ACSL4, GPX4, and IDO underscores their potential involvement in the pathogenesis of RSA. These findings provide critical insights into the metabolic mechanisms underlying RSA and suggest promising targets for diagnostic and therapeutic interventions.

目的本研究旨在确定复发性自然流产（RSA）患者蜕膜组织与正常孕妇蜕膜组织在代谢方面的差异，并识别富集途径。采用高效液相色谱-质谱联用技术（HPLC-MS）对蜕膜组织进行非靶向代谢组学分析。采用主成分分析法（PCA）和正交偏最小二乘判别分析法（OPLS-DA）来鉴定差异代谢物。利用京都基因和基因组百科全书（KEGG）数据库进行了途径富集分析，以阐明相关的代谢途径。利用定量聚合酶链反应（qPCR）评估了与这些通路相关的关键蛋白的表达水平，包括酰基-CoA合成酶长链家族成员4（ACSL4）、谷胱甘肽过氧化物酶4（GPX4）和吲哚胺2,3-二氧化酶（IDO）。结果共鉴定出54种代谢物在RSA患者和正常对照组的蜕膜组织中存在显著差异，对应于29种显著富集的代谢通路（P<0.05）。在 RSA 患者中，ACSL4 的表达明显上调，而 GPX4 和 IDO 的表达则明显下调（P<0.05）。ACSL4、GPX4和IDO的表达改变强调了它们在RSA发病机制中的潜在参与。这些发现提供了对RSA基础代谢机制的重要见解，并为诊断和治疗干预提出了有前景的目标。

{"title":"Metabonomics analysis of decidual tissue in patients with recurrent spontaneous abortion","authors":"Zhihui Chen , Huifang Yin , Youmei Long , Huiling Zhu , Renmei Xiong , Xin Duan , Hongyu Liu , Jiada Li","doi":"10.1016/j.jri.2024.104398","DOIUrl":"10.1016/j.jri.2024.104398","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to delineate the metabolic differences and identify enriched pathways in the decidual tissue of patients with recurrent spontaneous abortion (RSA) compared to normal pregnant women.</div></div><div><h3>Methods</h3><div>A cohort of 25 RSA patients and 25 normal pregnant women was recruited for the study. Non-targeted metabolomic analysis of decidual tissue was conducted using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS). Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were employed to identify differential metabolites. Pathway enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to elucidate associated metabolic pathways. Quantitative polymerase chain reaction (qPCR) was utilized to assess the expression levels of key proteins related to these pathways, including acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), and indoleamine 2,3-dioxygenase (IDO).</div></div><div><h3>Results</h3><div>A total of 54 metabolites were identified with significant differences between the decidual tissues of RSA patients and normal controls, corresponding to 29 significantly enriched metabolic pathways (P<0.05). The expression of ACSL4 was markedly upregulated, while the expression of GPX4 and IDO were significantly downregulated in RSA patients (P<0.05).</div></div><div><h3>Conclusions</h3><div>This study elucidates substantial metabolic disruptions in the decidual tissue of RSA patients, identifying 54 differential metabolites and 29 enriched pathways. The altered expression of ACSL4, GPX4, and IDO underscores their potential involvement in the pathogenesis of RSA. These findings provide critical insights into the metabolic mechanisms underlying RSA and suggest promising targets for diagnostic and therapeutic interventions.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"167 ","pages":"Article 104398"},"PeriodicalIF":2.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142722120","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