Placenta最新文献

{"title":"Placental lesions induced by Omicron SARS-CoV-2 in a pregnant woman treated with anti-CD20","authors":"C. Dubucs ,&nbsp;N. Dupuis ,&nbsp;A. Jourdes ,&nbsp;P. Delobel ,&nbsp;C. Auzet ,&nbsp;N. Van Acker ,&nbsp;C. Pasquier ,&nbsp;J. Aziza","doi":"10.1016/j.placenta.2025.03.015","DOIUrl":"10.1016/j.placenta.2025.03.015","url":null,"abstract":"<div><div>Since the emergence of SARS-CoV-2 in 2020, specific placental lesions characterized by a triad of trophoblastic necrosis, chronic histiocytic intervillitis, and massive perivillous fibrin deposits have been documented during pregnancy. After the arrival of the Omicron variant in late 2021, no placental lesions were observed at our institution until a recent case in September 2024 involving an immunosuppressed patient treated with anti-CD20. In this case, pathological analysis revealed the classic lesion triad, with strong immunohistochemical positivity for SARS-CoV-2. This suggests that placental tropism persists in certain variants several years after the emergence of SARS-CoV-2, necessitating vigilance in monitoring potential complications, especially in immunocompromised patients, regardless of variant classification.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"165 ","pages":"Pages 1-3"},"PeriodicalIF":3.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mosaic STS gene deletions in chorionic villus samples are often confined to the placenta, and they differ in size from STS gene deletions in patients with X-linked Ichthyosis","authors":"Pernille Marker Rydder ,&nbsp;Lotte Andreasen ,&nbsp;Simon Horsholt Thomsen ,&nbsp;Uffe Birk Jensen ,&nbsp;Naja Becher ,&nbsp;Morten Dunø ,&nbsp;Ida Vogel","doi":"10.1016/j.placenta.2025.03.016","DOIUrl":"10.1016/j.placenta.2025.03.016","url":null,"abstract":"<div><h3>Objective</h3><div>This study presents several cases of mosaicism for <em>STS</em> gene deletions in uncultured chorionic villus samples analyzed with chromosomal microarray without prior trypsinization. We aimed to confirm these results with MLPA on the chorionic villus samples and to evaluate the presence of mosaicism in follow-up amniocentesis.</div></div><div><h3>Methods</h3><div>We retrospectively collected cases of prenatally identified <em>STS</em> gene deletions in chorionic villus samples and amniocenteses at Aarhus University Hospital. A subgroup with mosaic microarray results was analyzed with MLPA.</div></div><div><h3>Results</h3><div>Four non-mosaic (of which three were inherited) and 16 mosaic <em>STS</em> gene deletions were identified. Mosaicism was confirmed with MLPA in all cases suitable for MLPA analysis. All 10 mosaic cases with follow-up amniocentesis showed normal results. In general, <em>STS</em> gene deletions in a mosaic state were smaller in size and had breakpoints located within the common fragile site <em>FRAXB</em>, whereas non-mosaic <em>STS</em> deletions were larger with breakpoints located close to <em>VCX</em> genes. Deletion size differed significantly between mosaic cases of this study and <em>STS</em> gene deletions in patients with X-linked Ichthyosis reported in ClinVar.</div></div><div><h3>Conclusion</h3><div>We report and confirm several cases of placental mosaicism for <em>STS</em> gene deletions. All mosaic cases with follow-up amniocentesis were confined to the placenta. Mosaic deletions likely arose from strand breaks at the common fragile site <em>FRAXB</em>, whereas the classical non-mosaic genotype found in patients with X-linked Ichthyosis arises from non-allelic homologous recombination during meiosis. These results support the existing hypothesis that placental mosaicism for copy number variants likely arise in common fragile sites.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"165 ","pages":"Pages 16-22"},"PeriodicalIF":3.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Placental size at gestational week 27 and 37: The associations with pulsatility index in the uterine and the fetal-placental arteries” [Placenta 145C (2024) 45-50]","authors":"Carl Petter Skaar Kulseng ,&nbsp;Silje Sommerfelt ,&nbsp;Kari Flo ,&nbsp;Kjell-Inge Gjesdal ,&nbsp;Helene Fjeldvik Peterson ,&nbsp;Vigdis Hillestad ,&nbsp;Anne Eskild","doi":"10.1016/j.placenta.2025.03.011","DOIUrl":"10.1016/j.placenta.2025.03.011","url":null,"abstract":"","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"164 ","pages":"Page 49"},"PeriodicalIF":3.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143681224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indole-3-lactic acid derived from tryptophan metabolism promotes trophoblast migration and invasion by activating the AhR/VCAN pathway","authors":"Yingying Wei ,&nbsp;Mengtian Wei ,&nbsp;Lu Zhang ,&nbsp;Linyan Jia ,&nbsp;Xiaojie Huang ,&nbsp;Tao Duan ,&nbsp;Qizhi He ,&nbsp;Kai Wang","doi":"10.1016/j.placenta.2025.03.014","DOIUrl":"10.1016/j.placenta.2025.03.014","url":null,"abstract":"<div><h3>Background</h3><div>Preeclampsia (PE) is a life-threatening condition that is unique to human pregnancy, and it is a leading cause of maternal and neonatal morbidity and mortality. Currently, the only definitive treatment for PE is delivery of the placenta. Several studies have suggested that the gut microbiota and its derived metabolites may be associated with PE. Our previous work indicated that the level of indole-3-lactic acid (ILA), which is a metabolite derived from tryptophan (Trp) metabolism in the gut, is increased in PE patients. However, the effects of ILA on trophoblast function and its underlying mechanisms remain largely unknown.</div></div><div><h3>Methods</h3><div>Transwell assays were conducted to assess the effects of ILA on trophoblast migration and invasion. Moreover, the aryl hydrocarbon receptor (AhR) signaling pathway was examined by qRT-PCR, western blotting and siRNA transfection. Additionally, RNA-seq analysis was performed to explore the mechanism underlying the ILA-mediated effects on trophoblast function. Finally, <em>in vivo</em> trophoblast invasion was evaluated through immunohistochemical analysis.</div></div><div><h3>Results</h3><div>Our data demonstrated that ILA promoted HTR-8/SVneo cell migration and invasion through AhR signaling pathway activation. Mechanistically, VCAN upregulation played a key role in mediating the effects of ILA on trophoblasts after AhR activation. Notably, ILA supplementation improved spiral artery remodeling and increased trophoblast invasion in PE-like mice, primarily by increasing VCAN levels. <strong>Conclusions</strong>: These data strongly suggest that elevated ILA in PE serve as a protective mechanism against trophoblast dysfunction. Therefore, we propose that ILA may be a novel and promising therapeutic approach for treating PE by enhancing trophoblast functions.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"165 ","pages":"Pages 4-15"},"PeriodicalIF":3.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Down-regulation of MYO1A inhibits trophoblast cell proliferation and migration through SMURF2/Hedgehog signaling pathway and leads to fetal growth restriction","authors":"Jie Wu ,&nbsp;Jiahui Fu ,&nbsp;Xinyun Li ,&nbsp;Fu Xiong ,&nbsp;Fang Yang","doi":"10.1016/j.placenta.2025.03.013","DOIUrl":"10.1016/j.placenta.2025.03.013","url":null,"abstract":"<div><h3>Introduction</h3><div>Fetal growth restriction (FGR) is most commonly related to insufficient placental perfusion caused by insufficient trophoblast proliferation and migration. Myosin Ia, encoded by the gene <em>MYO1A</em>, plays an important role in cytoskeleton recombination and cell movement. In this study, we found that downregulation of <em>MYO1A</em> inhibits Hedgehog (Hh) signaling by interacting with <em>SMURF2</em> in choriocarcinoma cells, leading to FGR.</div></div><div><h3>Methods</h3><div>A total of 59 placenta samples (26 FGR placentas and 33 normal placentas) were collected. The expression of <em>MYO1A</em> in placental tissues of the two groups was detected by qRT-PCR and Western blotting. The proliferation ability of choriocarcinoma cell lines HTR-8/SVneo and JEG3 was tested by CCK8 and colony formation experiments, and the migration ability was tested by transwell and wound healing experiments. Co-immunoprecipitation assay is used to verify the interaction between myosin Ia and <em>SMURF2</em>.</div></div><div><h3>Result</h3><div>We found that <em>MYO1A</em> expression was significantly lower in the placentas of pregnant women with FGR than in normal pregnant women. Moreover, the knockdown of <em>MYO1A</em> has been observed to inhibit choriocarcinoma cells proliferation and migration. Downregulation of <em>MYO1A</em> inhibits Hh signaling by reducing <em>SMURF2</em> expression.</div></div><div><h3>Discussion</h3><div>Our findings suggest that FGR is associated with a down-regulation of <em>MYO1A</em>, which may affect the Hh pathway through its interaction with <em>SMURF2</em>. This provides clues for a deeper understanding of the specific mechanisms underlying FGR.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"164 ","pages":"Pages 73-83"},"PeriodicalIF":3.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A locus control region generates distinct active placental lactogen and inactive growth hormone gene domains in term placenta that are disrupted with obesity","authors":"Yan Jin ,&nbsp;Ian McNicol ,&nbsp;Peter A. Cattini","doi":"10.1016/j.placenta.2025.03.012","DOIUrl":"10.1016/j.placenta.2025.03.012","url":null,"abstract":"<div><h3>Introduction</h3><div>Placental villi include an outer syncytiotrophoblast (STB) layer and an inner layer of cytotrophoblasts (CTBs) that fuse to generate the STB layer in pregnancy. While activation of the locus containing the human (h) placental lactogen (hPL) genes (<em>hPL-A</em>/<em>CSH1</em> and <em>hPL-B</em>/<em>CSH2</em>) begins in the CTBs, their expression in the STB requires epigenetic modifications and interactions between locus control region (LCR) and gene regulatory sequences. No factor that limits or facilitates hPL LCR/gene interactions for locus activation is reported. The paternally-expressed gene 3 (PEG3/PW1) transcription factor was pursued as a candidate. PEG3 is expressed by villous CTBs but not the STB and putative binding sites were identified in hPL-related sequences.</div></div><div><h3>Methods</h3><div>PEG3 expression was assessed in multiple cell types including in CTB-like JEG-3 cells. PEG3 binding was also assessed in JEG-3 cells and term placenta samples from women with or without maternal obesity, where chromosomal architecture of the hPL gene locus was also examined.</div></div><div><h3>Results</h3><div>In JEG-3 cells, PEG3 was found to bind to hypersensitive site (HS III-V) sequences within the LCR. Knockdown of PEG3 in these cells resulted in increased hPL gene expression. In term placenta, PEG3 binding at placenta-specific HS IV was increased with maternal obesity, where a decrease in hPL RNA levels is seen, while PEG3 binding was reduced in women with obesity who develop insulin-treated gestational <em>diabetes mellitus</em> (O/GDM + Ins), where increased hPL gene expression is observed. Chromatin conformation capture revealed distinct hPL gene domain interactions that are modified with maternal obesity but largely reversed in O/GDM + Ins, correlating with PEG3 binding.</div></div><div><h3>Discussion</h3><div>Decreased PEG3 binding may be required for hPL domain generation and expression during CTB to STB transition.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"164 ","pages":"Pages 64-72"},"PeriodicalIF":3.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Explorative 3-D culture of early secondary follicles in a time lapse system for up to 36 days gives valuable, but limited insights in follicular development","authors":"Andreas Schallmoser,&nbsp;Norah Emrich,&nbsp;Rebekka Einenkel ,&nbsp;Nicole Sänger","doi":"10.1016/j.placenta.2025.03.007","DOIUrl":"10.1016/j.placenta.2025.03.007","url":null,"abstract":"<div><h3>Background</h3><div>Cryopreservation of ovarian cortical tissue is an important option for female fertility preservation.</div><div>This is particularly valuable for cancer patients who need to be treated urgently with chemotherapy, leaving no time for hormonal stimulation. The transfer of malignant cells in certain cancers remains as a potential risk after freezing, thawing and transplantation of ovarian tissue while isolation and <em>in vitro</em> growth (IVG) of follicles could be a safe alternate approach of female fertility protection.</div></div><div><h3>Methods</h3><div>Ovarian cortex tissue was frozen, thawed and cultured for 8 days prior to isolating and embedding of early secondary follicles in a 3D matrix, suitable for time lapse monitoring for up to 36 days. Continuous growth of a theca-like cell layer and extrafollicular protrusions were visually evaluated with a permanent monitoring system facilitating real-time follicular development without deviations in the culture conditions. Occurrence of theca cell growth was visually characterized by extrafollicular formation of cells, beyond the outer follicle boundaries. To validate the results observed by time-lapse monitoring, live cell imaging was conducted and determined with immunofluorescence staining.</div></div><div><h3>Results</h3><div>Individual follicles significantly increased in size over time. Time-lapse video monitoring revealed extending and retracting of filopodia-like structures in the outer follicular region adjacent to the 3D environment. Theca-like cells and actin components of filopodia-like structures were identified based on immunofluorescence staining.</div></div><div><h3>Conclusions</h3><div>Time lapse monitoring of 3-D cultured follicles is a promising explorative approach to obtain valuable visual insights regarding the many facets of follicular growth and to optimize follicular culture conditions towards a clinical application. As the study is limited by a lack of mechanistic insights into theca cell differentiation and filopodia function, additional studies are necessary to validate the preliminary results of this approach.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"164 ","pages":"Pages 50-63"},"PeriodicalIF":3.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143681225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic intervillositis of unknown etiology in patients with recurrent pregnancy loss: Impact on reproductive outcomes, treatment efficacy, and recurrence rates","authors":"Bahi Fayek ,&nbsp;Yang Doris Liu ,&nbsp;Arshdeep Sidhu ,&nbsp;Kimia Ziafat ,&nbsp;Maya Geerts ,&nbsp;Faten F. AbdelHafez ,&nbsp;Jefferson Terry ,&nbsp;Mohamed A. Bedaiwy","doi":"10.1016/j.placenta.2025.03.009","DOIUrl":"10.1016/j.placenta.2025.03.009","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aimed to examine the influence of chronic intervillositis of unknown etiology (CIUE) on reproductive outcomes in patients with recurrent pregnancy loss (RPL), determine treatment effectiveness in future pregnancies, and estimate the CIUE recurrence rate.</div></div><div><h3>Materials and methods</h3><div>This retrospective study examined patients with RPL, categorizing them into CIUE and non-CIUE groups. Impact of CIUE on reproductive outcomes was assessed both cross-sectionally and longitudinally. A log-rank survival analysis was conducted to assess the effectiveness of various treatments on achieving ongoing pregnancies or live births following an initial episode of CIUE. Lastly, CIUE recurrence rate was evaluated.</div></div><div><h3>Results</h3><div>A total of 394 patients were included in the study: 23 in the CIUE group and 371 in the non-CIUE group. No significant differences were observed between the groups regarding baseline characteristics. Adjusted logistic regression showed that patients with CIUE had higher odds of experiencing preterm birth compared to non-CIUE patients (odds ratio [OR] = 3.15; 95 % confidence interval [CI]: 1.07–9.22). With each additional pregnancy, the non-CIUE group had 75 % increased odds of achieving live birth (OR 1.75; 95 % CI: 1.49–2.06), while the CIUE group's increase was not significant (OR 1.32; 95 % CI: 0.86–2.05). Additionally, the odds of stillbirth associated with additional pregnancies increased by 85 % in the CIUE group (OR 1.85; 95 % CI: 1.03–3.36), yet not significant in the non-CIUE group (OR 1.14; 95 % CI: 0.90–1.45). CIUE-treated patients had higher odds of achieving live birth or ongoing pregnancy after 24 months (P = 0.0491). CIUE recurred in 21.7 % of patients.</div></div><div><h3>Conclusion</h3><div>In the RPL population, CIUE adversely affected the reproductive outcomes. Despite its high recurrence rate, prophylactic treatment showed potential in improving outcomes.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"164 ","pages":"Pages 41-48"},"PeriodicalIF":3.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The inhibition of placental mTOR signaling leads to fetal growth restriction with abnormal glucose metabolism in different anatomical regions of placentas","authors":"Qian Xu ,&nbsp;Jingjing Wang ,&nbsp;Yajing Li ,&nbsp;Hui Lei ,&nbsp;Ni Jin ,&nbsp;Jie Lu ,&nbsp;Chenxi Qian ,&nbsp;Jianhua Zhang ,&nbsp;Jie Dong ,&nbsp;Xiaohong Wang","doi":"10.1016/j.placenta.2025.03.008","DOIUrl":"10.1016/j.placenta.2025.03.008","url":null,"abstract":"<div><h3>Introduction</h3><div>Fetal growth restriction (FGR) is a common pregnancy complication with significant impact on obstetric and birth outcomes. Increasing evidence shows that the inhibition of placental mechanistic target of rapamycin (mTOR) signaling is closely related to FGR. However, the pathogenesis of FGR is not fully consistent presently, which is subject to the methodological divergence.</div></div><div><h3>Methods</h3><div>Rapamycin was used to construct the FGR mouse model. Hematoxylin &amp; eosin (HE) and periodic acid-schiff (PAS) staining were used to analyze the morphology of mouse placenta. Western blot was used to analyze the expression levels of glucose transporters and key enzymes associated with glycogen metabolism in human/mouse placental tissues in different anatomic layers. HTR-8 cells were treated with dimethyl sulfoxide (DMSO) or rapamycin (2 mM) for 24 h. Cell viability was detected by CCK8 kit. In addition, glycogen concentration in placental tissue or cell samples was detected by Glycogen Assay Kit.</div></div><div><h3>Results</h3><div>Firstly, we observed a significant reduction of glucose content in different anatomical regions of human small-for-gestational-age (SGA) placenta, also glucose metabolism was undermined to some extent. Then, we found that FGR placentas showed abnormal morphological changes, the glycogen levels in FGR placentas were significantly reduced by quantitative detection. Meanwhile, the expression levels of glucose transporters, Gys1 and p-Gsk3β in FGR placentas were reduced compared to controls. The HTR-8 cells treated with rapamycin revealed decreasing mTOR activity and glycogen levels. In addition, glucose transporter, GYS1, p-GSK3β expressions were all significantly reduced and t-GSK3β level was significantly elevated.</div></div><div><h3>Discussion</h3><div>Overall, our data indicate that inhibition of placental mTOR signaling may contribute to the occurrence of FGR by altering glucose metabolism.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"164 ","pages":"Pages 31-40"},"PeriodicalIF":3.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Placental weight as a predictor of future health: Insights from a large-scale genome-wide association study","authors":"Qinyi Zhang ,&nbsp;Tianhan Xu ,&nbsp;Sihui Yu ,&nbsp;Sufang Wu ,&nbsp;Ye Yang ,&nbsp;Hao Wu ,&nbsp;Jiawen Zhang","doi":"10.1016/j.placenta.2025.03.006","DOIUrl":"10.1016/j.placenta.2025.03.006","url":null,"abstract":"<div><h3>Introduction</h3><div>Placental weight has been associated with various adult-onset diseases, but the causal relationships and underlying mechanisms remain unclear.</div></div><div><h3>Methods</h3><div>This two-sample Mendelian randomization (MR) study utilized genome-wide association study (GWAS) data from multiple independent cohorts, primarily of European ancestry. The analysis included over 1.8 million individuals for type 2 diabetes mellitus (T2DM) outcomes. Data from four independent cohorts were used for validation. The inverse variance-weighted method was used for primary analysis, with weighted median, weighted mode, and MR-Egger regression for sensitivity analyses.</div></div><div><h3>Results</h3><div>Each standard deviation increase in genetically predicted placental weight was associated with T2DM (β = −0.109, 95 % CI: −0.184 to −0.034), basal cell carcinoma (β = 0.130, 95 % CI: 0.016 to 0.245), acute upper respiratory infections (β = −0.062, 95 % CI: −0.113 to −0.011), neurological diseases (β = −0.009, 95 % CI: −0.014 to −0.003), and endometrial cancer (β = −0.561, 95 % CI: −0.961 to −0.161). Placental weight also showed significant negative associations with blood glucose levels (β = −0.102, 95 % CI: −0.200 to −0.004). Mediation analyses revealed that dried fruit intake mediated 14.68 % of the total effect on T2DM risk, while immune cell phenotype analysis identified HLA DR on CD33dim HLA DR + CD11b + as a potential mediator in the causal pathway.</div></div><div><h3>Conclusion</h3><div>This study provides genetic evidence for a causal relationship between placental weight and T2DM risk, mediated partly through dietary habits and immune pathways. These findings suggest that early-life placental development may influence long-term metabolic health, highlighting the importance of prenatal care in preventing adult-onset diseases.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"164 ","pages":"Pages 10-20"},"PeriodicalIF":3.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}