Molecular human reproduction最新文献

{"title":"Mechanical signal-mediated mitochondria-endoplasmic reticulum contacts modulate Leydig cell testosterone biosynthesis during testis development.","authors":"Jiahong Wu, Ruiling He, Zeyu Xu, Huan Yang, Yupeng Guan, Lu Sun, Wantong Lv, Jiayu Huang, Jiancheng Wang","doi":"10.1093/molehr/gaaf017","DOIUrl":"https://doi.org/10.1093/molehr/gaaf017","url":null,"abstract":"<p><p>In males, 95% of testosterone is synthesized by Leydig cells, and a deficiency in this synthesis will cause metabolic disorders and multiple organ dysfunction. Testosterone deficiency is not only affected by aged or diseased Leydig cells, which have been studied extensively, but is also closely related to the development of the testis. At present, the focus on the mechanism of testis development includes epigenetic and hormone regulation. However, testicular development is constrained by the external tough tunica albuginea, suggesting that mechanical signals may also play an important role in the regulation of testis development; however, this is not yet well understood. In this in-vitro study, we found that a gradual increase in extracellular substrate stiffness for testis development leads to the activation of mechanical signals to promote cytoskeleton remodeling. Eventually, the mechanical signal mediate changes in the mitochondrial-endoplasmic reticulum and affect the synthesis of testosterone in Leydig cells. Through organoid and animal experiments, we found that targeting mechanical signaling pathways that regulate testosterone biosynthesis is feasible. This provides a new angle for further exploration of testis development and new insights into how substrate stiffness affects the testis, raising new clues for clinical applications.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151255","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":"Alterations in the abundance of protamine proteoforms related to sperm chromatin packaging, obesity and age in normozoospermic men.","authors":"Judit Castillo, Marina Gay, Alberto De La Iglesia, Gianluca Arauz-Garofalo, Mar Vilanova, Marina Leiva, Juan Manuel Corral, Marta Guimerà, Dolors Manau, Marta Vilaseca, Meritxell Jodar, Rafael Oliva","doi":"10.1093/molehr/gaaf019","DOIUrl":"https://doi.org/10.1093/molehr/gaaf019","url":null,"abstract":"<p><p>Protamines are considered among the most relevant sperm proteins because of their functional implications on paternal genome packaging and protection. Although the proteomic evaluation of protamines is technically challenging, mass spectrometry-based studies have shown a complex population of protamine proteoforms in the human sperm. This included intact, truncated and modified forms for protamine 1 (P1) and mature and immature components of protamine 2 family (P2). However, it is still unknown whether global or specific protamine proteoforms levels may be unbalanced under conditions that may impair paternal chromatin maturity and epigenetic information. In this study, protamines from normozoospermic men stratified according to body mass index, age and chromatin maturity (assessed through the P1/P2 ratio derived from acid-urea electrophoresis) were evaluated using a refined top-down mass spectrometry protocol for protamine proteoform quantification and comparative analysis. Accumulation of the P2 immature forms HPS1 and HPI2 was significantly associated with abnormally high P1/P2 ratios, suggesting either impaired eviction of P2 immature forms or defective P2 processing during spermatogenesis in these men clinically classified as normozoospermic. When considering weight and age as factors, P1 was the only affected protamine. Sperm from obese men, which were found to be exposed to high levels of oxidative damage derived from lipid peroxidation, showed mass shift(s) of + 61 Da from the unmodified P1 protein sequence. Men of advanced age showed a specific loss of diphosphorylated P1, mainly on Ser 11 and 22. Our results allow the hypothesis that protamine proteoforms in the male gamete act as additional layers of epigenetic information, the alteration of which might be related to some cases of impaired sperm function.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136221","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":"Mosaicism is more than meets the eye: transcriptional consequences of blastocyst mosaicism.","authors":"Brandon A Wyse, Noga Fuchs Weizman, Rima Kharonsky, Svetlana Madjunkova, Clifford L Librach","doi":"10.1093/molehr/gaaf018","DOIUrl":"https://doi.org/10.1093/molehr/gaaf018","url":null,"abstract":"<p><p>Blastocyst mosaicism is increasingly detected due to advances in preimplantation genetic testing for aneuploidy (PGT-A). While some mosaic embryos result in a live birth, there are reports of altered implantation potential. Various approaches are needed to better understand their developmental uniqueness, including their transcriptomic profile. This study aimed to profile the transcriptomic signatures of mosaic embryos and investigate how mosaicism influences global gene expression. Utilizing a novel method enabling simultaneous sequencing of both genomic (g)DNA, for PGT-A, and mRNA, we analyzed 76 blastocysts from 60 IVF-ICSI patients, including 29 euploid, 23 mosaic and 24 aneuploid embryos. Transcriptomic analysis revealed that 14% of annotated genes are differentially expressed (DE) between mosaic and euploid embryos, with the majority of genes being upregulated in mosaic embryos. We further divided the mosaic cohort into mosaic-gain (mosaic trisomy) and mosaic-loss (mosaic monosomy) embryos and identified a core set of 902 DE genes that are shared regardless of the direction of the mosaicism (gain or loss). Pathway analysis revealed significant upregulation in pathways associated with cell cycle regulation, mitochondrial respiration, DNA repair and vesicle transport. Following leading edge analysis, genes previously annotated to be involved in embryo implantation were downregulated in mosaic embryos. Separately, in a subset of aneuploid embryos, we identified gene dosage effects; while embryos with trisomies 18 and 21 exhibit transcriptional signatures similar to euploid embryos, those with trisomies 16 and 22 demonstrate more divergent profiles, correlating with their previously reported implantation and clinical outcomes. These findings enhance current literature on the transcriptomic consequences of mosaicism in the trophectoderm of embryos. They suggest that mosaic blastocysts exhibit transcriptional signatures that reflect their mixed chromosomal composition, potentially influencing their implantation efficiency and developmental potential. Despite the inherent cellular stress, a proportion of mosaics retain developmental resilience, underscoring the complexity of embryo selection in ART.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094165","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":"Single-cell metabolomics reveals that bisphosphoglycerate mutase influences oocyte maturation through glucose metabolism.","authors":"Jing Wang, Qiang Liu, Zhiqiang Yan, Qianying Guo, Yixuan Wu, Ling Ding, Tianyi Liao, Jiahui Fan, Jie Qiao, Liying Yan","doi":"10.1093/molehr/gaaf009","DOIUrl":"https://doi.org/10.1093/molehr/gaaf009","url":null,"abstract":"<p><p>The spatiotemporal turnover of metabolites is essential for oocyte maturation, embryonic development, and cell lineage differentiation. Here, we analyzed the metabolic profiles of individual living mouse oocytes and studied how bisphosphoglycerate mutase (BPGM), an important maternal factor, influences metabolite regulation during oocyte maturation. We found that BPGM is expressed in mouse follicles, oocytes, and embryos, as well as in human embryos. Notably, deletion of Bpgm significantly reduced the rate of oocyte maturation and reduced mouse fertility, which was observed as reduced pups per litter. Also, the expression levels for meiosis-related genes and genes related to glucose metabolic pathways (glycolysis, tricarboxylic acid cycle, and pentose phosphate pathway) were altered in BPGM-deficient mouse oocytes. We used a highly sensitive, live-cell sampling approach to carry out metabolite assays using induced nanoelectrospray-ionization mass spectrometry technology on 1 picolitre of aspirated cytoplasm from oocytes. BPGM gene disruption impaired glucose metabolism pathways, tyrosine metabolism, and amino acid biosynthesis. Together, our findings indicate that Bpgm participates in oocyte and embryo development, and we demonstrate the feasibility of studying metabolite composition and other phenotypic features of single oocytes.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":"31 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978830","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":"Roles of chromosomal and gonadal sex in the fetal and placental responses to maternal food restriction in mice.","authors":"Jess C Hercus, Daniel Alejandro Salcedo Rubio, Maria Elisa Osorio Nieto, Cheayeong Keum, Qi Wang, John A Macdonald, Jordan S Scott, Emily R J Lucas, Julian K Christians","doi":"10.1093/molehr/gaaf015","DOIUrl":"10.1093/molehr/gaaf015","url":null,"abstract":"<p><p>It is hypothesized that male fetuses are more vulnerable to in utero insults than females due to different growth strategies, and that the placenta contributes to these sex differences. We examined sex differences in the fetal and placental responses to maternal food restriction (∼60% of ad libitum) beginning mid-gestation (Day 11.5). To dissect the roles of chromosomal and gonadal sex, we used the Four Core Genotypes mouse model, which combines deletion of the testis-determining Sry gene from the Y chromosome and autosomal insertion of the Sry gene, such that XX gonadal males and XY gonadal females are produced in addition to XX females and XY males. Food restriction reduced fetal and placental weights but had no effect on the number of viable conceptuses. However, this effect did not differ between gonadal male and female, or between XX and XY, conceptuses. Sex differences in gene expression in both the labyrinth and the combined junctional zone/decidua, as assessed by RNA sequencing, were due entirely to chromosomal sex and not gonadal sex. Food restriction affected the expression of 525 and 665 genes in the labyrinth and the junctional zone/decidua, respectively. However, these effects of food restriction did not differ by gonadal or chromosomal sex when assessed for statistical interactions. In contrast, when analyzing XX and XY placentas separately, hundreds of genes were affected by food restriction in one sex but not in the other, including hundreds of genes not found to be significant in the combined analyses. However, estimated effect sizes were generally similar for XX and XY placentas, suggesting that these sex-stratified analyses greatly exaggerated the extent of sex-dependent responses. Overall, we did not find evidence of the hypothesized sex differences in fetal growth strategy and found that sex differences in placental gene expression were largely due to chromosomal sex.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019777","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":"Cellular prion: a novel regulator of decidual cell function at the maternal-fetal interface.","authors":"Swarnali Dey, Tamal Kanti Gope, Rupasri Ain","doi":"10.1093/molehr/gaaf016","DOIUrl":"10.1093/molehr/gaaf016","url":null,"abstract":"<p><p>Cellular prion (PRNP) is a GPI-anchored extrinsic membrane glycoprotein, which has been implicated in mouse decidualization. However, the molecular function of this protein in mouse decidua is not known. In this article, we have characterized and elucidated the possible role of PRNP in mouse decidua. We demonstrated that PRNP expression is evident on embryonic day (E) 6.5 to E9.5 across the primary decidual zone (PDZ) in the mouse implantation site. As gestation progressed, PRNP continued to be expressed in the receding decidua, up to E17.5. shRNA-mediated knockdown of PRNP on E5.5 through E7.5 led to decreased expression of tight junction proteins (TJPs) in PDZ in vivo. These included Cingulin, Afadin, Catenin-α1, Lethal (2) giant larvae protein homolog 1, Claudin-5, and ICAM1. Furthermore, PRNP-positive decidual cells showed augmented expression of autophagic machinery. PRNP knockdown curtailed expression of autophagy-related genes in decidua in vivo. Our results highlight hitherto unknown novel functions of PRNP: (i) an inducer of TJPs at PDZ, which protects the developing embryo and (ii) a decision-maker protein between life and death in decidual cells.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972247","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":"Effects of chronic particulate matter exposure on endometriosis-associated signaling pathways and disease progression.","authors":"Gee Soo Jung, Jae Hoon Lee, Min Jung Lee, Inha Lee, Hyemin Park, Nara Kim, Ji-Ye Kim, Wooseok Im, SiHyun Cho, Young Sik Choi","doi":"10.1093/molehr/gaaf013","DOIUrl":"https://doi.org/10.1093/molehr/gaaf013","url":null,"abstract":"<p><p>Exposure to PM2.5 (particulate matter <2.5 μm) has been implicated in increasing the risk of endometriosis and worsening its symptoms. However, the molecular mechanisms and direct associations remain unclear. This study explored whether PM2.5 contributes to the onset or progression of endometriosis using in vitro and in vivo models. Endometrial (EM) cells from women without endometriosis were cultured to the second passages (P2) with or without exposure to PM2.5 at a concentration of 200 µg/ml (N = 5 for each group). Z-stack confocal imaging confirmed PM accumulation in the nucleus and cytoplasm of exposed EM cells. Initial PM exposure at the primary passage (P0) led to decreased proliferation, migration, anti-apoptosis, and oxidative stress, accompanied by downregulation of associated pathways. However, repeated PM exposure during subculturing to P2 led to increased proliferation, enhanced anti-apoptotic activity, and elevated oxidative stress. Given the similarity of these gene expression alterations to those observed in endometriosis, an endometriosis-induced mouse model was established to assess the potential of repeated PM exposure to exacerbate the condition in vivo. To investigate the in vivo effects, an endometriosis-induced mouse model was developed using female C57BL/6 mice exposed to low (10 mg/kg/day) or high (20 mg/kg/day) doses of PM2.5 for 4 weeks (n = 6 for each group). PM exposure significantly enlarged endometriotic lesions compared to controls (no PM exposure). Upregulated gene expression in endometriotic lesions included anti-apoptotic (Bcl2/Bax), proliferative (p-ERK), inflammatory (p-NF-κB, p-c-jun, IL-6, IL-1β), and migration (MMP-2, MMP-9) markers. PM exposure altered estrogen receptor (ER) expression, resulting in a decreased ERα/ERβ ratio in both dose groups. The control group exhibited a ratio of 1.03 ± 0.09, while the low-dose and high-dose mice had ratios of 0.57 ± 0.08 (P = 0.02) and 0.46 ± 0.26 (P = 0.03), respectively. In conclusion, PM2.5 exposure alters gene expression related to cell growth, survival, oxidative stress, and migration in EM cells and exacerbates endometriotic lesions in vivo, likely through ER modulation. These findings suggest PM2.5 may contribute to other estrogen-dependent conditions, such as leiomyoma or adenomyosis, by influencing ER pathways.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":"31 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971667","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":"Protein-targeting reverse genetic approaches: the future of oocyte and preimplantation embryo research.","authors":"Nicole J Camlin","doi":"10.1093/molehr/gaaf008","DOIUrl":"10.1093/molehr/gaaf008","url":null,"abstract":"<p><p>Reverse genetic approaches are the standard in molecular biology to determine a protein's function. Traditionally, nucleic acid targeting via gene knockout (DNA) and knockdown (RNA) has been the method of choice to remove proteins-of-interest. However, the nature of mammalian oocyte maturation and preimplantation embryo development can make nucleic acid-targeting approaches difficult. Gene knockout allows time for compensatory mechanisms and secondary phenotypes to develop which can make interpretation of a protein's function difficult. Furthermore, genes can be essential for animal and/or oocyte survival, and therefore, gene knockout is not always a viable approach to investigate oocyte maturation and preimplantation embryo development. Conversely, RNA-targeting approaches, i.e. RNA interference (RNAi) and morpholinos, rely on protein half-life and therefore are unable to knockdown every protein-of-interest. An increasing number of reverse genetic approaches that directly target proteins have been developed to overcome the limitations of nucleic acid-based approaches, including Trim-Away and auxin-inducible degradation. These protein-targeting approaches give researchers exquisite and fast control of protein loss. This review will discuss how Trim-Away and auxin-inducible degradation can overcome many of the challenges of nucleic acid-based reverse genetic approaches. Furthermore, it highlights the unique research opportunities these approaches afford, such as targeting post-translationally modified proteins.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12000532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657685","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":"Human platelet-rich plasma promotes primordial follicle activation via the PI3K/Akt signaling pathway.","authors":"Yashuang Weng, Wenbo Zhang, Fan Qu, Zehua Deng, Xiaodan Zhang, Shuang Liu, Hongwei Wei, Tiantian Hao, Longwei Gao, Meijia Zhang, Yuezhou Chen","doi":"10.1093/molehr/gaaf007","DOIUrl":"10.1093/molehr/gaaf007","url":null,"abstract":"<p><p>The activation of dormant primordial follicles is a promising method to improve the fertility of premature ovarian insufficiency (POI) patients. Many experiments from both human and animal studies suggest that human platelet-rich plasma (hPRP) may restore ovarian function and promote follicle growth. However, the underlying mechanisms remain unclear. In the current study, our results demonstrate that hPRP significantly increased the number of growing follicles and promoted the proliferation of granulosa cells in cultured mouse ovaries. hPRP also significantly increased the protein levels of phosphorylated protein kinase B (p-Akt) and forkhead box O3a (p-FOXO3a), as well as the number of oocytes with FOXO3a nuclear export in cultured mouse ovaries. Immunofluorescence results showed that in vitro treatment with hPRP significantly increased the fluorescence intensity of p-Akt in oocytes. The inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway by LY294002 blocked the hPRP-induced increase in the number of growing follicles in cultured mouse ovaries. Furthermore, hPRP injected i.p. or added to the medium significantly increased the number of growing follicles and the protein levels of p-Akt in the ovaries of newborn mice and in cultured human ovarian tissues. Taken together, our findings from mouse and human experiments indicate that hPRP promotes the activation of primordial follicles through the PI3K/Akt signaling pathway in oocytes.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633640","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":"Exploring and validating the marmoset as a primate model for chromosomal instability in early development.","authors":"Andrew Cearlock, Hubert Mysliwiec, Margarita Agarsheva, Joanna Krzyspiak, Mohammad Zeeshan Ozair, Ali H Brivanlou, Min Yang","doi":"10.1093/molehr/gaaf012","DOIUrl":"10.1093/molehr/gaaf012","url":null,"abstract":"<p><p>Aneuploidy in embryos poses a major barrier to successful human reproduction, contributing to nearly 50% of early miscarriages. Despite its high prevalence in human embryos, the molecular mechanisms regulating aneuploid cell fate during development remain poorly understood. This knowledge gap persists due to ethical constraints in human embryo research and the limitations of existing animal models. In this study, we identified the New World primate marmoset (Callithrix jacchus) as a suitable model for investigating aneuploidy. By calling copy number variants from single-cell RNA-sequencing data of marmoset embryonic cells, we identified heterogeneous aneuploidy, indicating chromosomal instability (CIN) in marmoset preimplantation embryos. Furthermore, marmoset aneuploidy displayed lineage-specific behavior during gastruloid differentiation, similar to humans, suggesting a conserved regulatory mechanism in lineage specification. To develop a more pluripotent cell line to study early specification, we established an efficient approach for generating naïve-like marmoset pluripotent stem cells (cjPSCs). These cells resemble preimplantation epiblast-like cells and exhibit inherent CIN. Transcriptome analysis identified potential pathways contributing to aneuploidy during early embryogenesis, including the downregulation of cell cycle checkpoint signaling and the upregulation of autophagy pathways. Additionally, we found no significant effect of spontaneously occurring aneuploidy in cjPSCs on blastoid formation, suggesting that the consequences of aneuploidy become evident only after gastrulation, with preimplantation lineages exhibiting a higher tolerance for genomic instability. Unexpectedly, aneuploidy enhanced cavity formation during blastoid development, suggesting a potential role in facilitating efficient trophectoderm differentiation. Our findings validate the marmoset as a valuable model for studying CIN during early primate development and provide insight into the mechanisms underlying the prevalence of aneuploidy in primates. Naïve-like cjPSCs recapitulate key phenotypic traits of early embryonic cells, providing a robust system for studying post-implantation aneuploid cell fates in vivo and serving as a foundation for future research in this field.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803874","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}