Renata K. Carvalho , Maingredy R. Souza , Akemy N. Nishimura , Edvaldo M. Silva , Cinthia R.B. Silva , Francisco S. Guimarães , Monica L. Andersen , Simone M.T. Sabóia-Morais , Renata Mazaro-Costa
{"title":"Post-weaning exposure to cannabidiol disrupts testicular cytoarchitecture and sperm quality in mice","authors":"Renata K. Carvalho , Maingredy R. Souza , Akemy N. Nishimura , Edvaldo M. Silva , Cinthia R.B. Silva , Francisco S. Guimarães , Monica L. Andersen , Simone M.T. Sabóia-Morais , Renata Mazaro-Costa","doi":"10.1016/j.reprotox.2025.108952","DOIUrl":"10.1016/j.reprotox.2025.108952","url":null,"abstract":"<div><div>Cannabidiol (CBD) is a natural cannabinoid with a wide range of potential therapeutic applications, including as an anticonvulsant and for the treatment of inflammatory conditions. It is known that CBD interacts with the endocannabinoid system, which plays a crucial role in various physiological functions. However, its effects on male reproduction have not yet been fully elucidated. Thus, the aim of this study was to evaluate the <em>in vivo</em> effects of CBD on testicular cytoarchitecture and sperm quality in mice. Twenty-one-day old male Swiss mice received intragastric doses of CBD (15 or 30 mg/kg/day) for 34 consecutive days. A control group received sunflower oil. Both doses of CBD reduced the number of Sertoli cells at stages VII–VIII, IX and XII of spermatogenesis. A significant decrease in proliferating cell nuclear antigen (PCNA)-positive spermatocytes at stages VII–VIII was observed in the CBD15 group. In the interstitial compartment of the testis, no significant differences were found in the diameter and volume of Leydig cell nuclei or in the immunostaining of these cells for PCNA in the control and CBD-treated groups. Both doses of CBD reduced the percentage of viable spermatozoa and the percentage of morphologically normal spermatozoa. These findings suggest that daily exposure to CBD may reduce sperm quality, and the mechanisms responsible may be related to perturbations in the endocannabinoid system during spermatogenesis.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"135 ","pages":"Article 108952"},"PeriodicalIF":3.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yue Han , Juan Dai , Jinxin Cheng , Yan He , Chengkun Zhao , Rui Li , Yaqin Zhang , Ling Zhang , Ting Zhou , Yuqin Shi
{"title":"Cadmium induces autophagy via IRE1 signaling pathway activated by Ca2 + in GC-2spd cells","authors":"Yue Han , Juan Dai , Jinxin Cheng , Yan He , Chengkun Zhao , Rui Li , Yaqin Zhang , Ling Zhang , Ting Zhou , Yuqin Shi","doi":"10.1016/j.reprotox.2025.108950","DOIUrl":"10.1016/j.reprotox.2025.108950","url":null,"abstract":"<div><div>Cadmium (Cd), an environmental toxicant, accumulates in the human body and damages the male reproductive system. To investigate the molecular mechanisms underlying Cd-induced reproductive toxicity, we used GC-2spd cells and treated them with CdCl<sub>2</sub>. Additionally, we added 2-APB (an inhibitor of the IP3R) and STF-083010 (an inhibitor of IRE1) to investigate whether they could ameliorate Cd-induced reproductive toxicity. Confocal microscopy and flow cytometry confirmed that CdCl<sub>2</sub>-treated GC-2spd cells displayed imbalance of calcium homeostasis, with upregulation of the expression of the IP3R, a key pathway for endoplasmic reticulum (ER) Ca<sup>2+</sup> release. Furthermore, the ER stress (ERS) effector protein IRE1 expression was also increased, suggesting that Cd activated ERS and the IRE1 pathway by disrupting calcium homeostasis. Previous studies have shown that ERS induces autophagy. We performed the MDC assay to detect autophagosome formation, revealing increased expression of autophagy-related proteins LC3-II/LC3-I and Beclin-1 in response to Cd treatment. In contrast, treatment with 2-APB and STF-083010 inhibited autophagy and mitigated cell death. This inhibitory effect may be due to 2-APB blocking IP3R-mediated Ca<sup>2+</sup> release, alleviating imbalance of calcium homeostasis, while STF-083010 inhibits IRE1, restoring ER homeostasis and reducing autophagy. These findings suggest that imbalance of calcium homeostasis activates the IRE1 pathway-mediated ERS, leading to excessive autophagy and male reproductive toxicity. Conversely, the addition of 2-APB and STF-083010 reversed these effects, synergistically restoring intracellular Ca<sup>2+</sup> homeostasis and inhibiting ERS to promote cell health. This study provides a new therapeutic strategy for Cd-induced male reproductive disorders.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"135 ","pages":"Article 108950"},"PeriodicalIF":3.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaowen Liu , Zewei Yu , Yangying Xu , Wei Xue , Xin Du , Guanghui Yuan , Xiaoxiao Wang , Yingxue Liu , Shuyuan Chen , Cuifang Hao , Duan Li
{"title":"A case-control study on the link between trace element exposure in follicular fluid and premature ovarian insufficiency","authors":"Xiaowen Liu , Zewei Yu , Yangying Xu , Wei Xue , Xin Du , Guanghui Yuan , Xiaoxiao Wang , Yingxue Liu , Shuyuan Chen , Cuifang Hao , Duan Li","doi":"10.1016/j.reprotox.2025.108947","DOIUrl":"10.1016/j.reprotox.2025.108947","url":null,"abstract":"<div><div>Premature ovarian insufficiency (POI), affecting 3.5 % of women under 40, significantly impacts reproductive health. The unknown etiology in over 50 % of POI cases impedes accurate diagnosis and treatment. Evidence shows that environmental agents can adversely affect health and reduce fertility. Trace elements are critical pollutants impacting human health. However, research on populations with POI and their links to these elements is limited. We enrolled 367 female patients, dividing them into a POI group and a control group. We employed ICP-MS to measure 25 trace elements in follicular fluid. Bayesian kernel machine regression analyzed combined exposure effects and restricted cubic splines evaluated the relationships between individual trace elements and ovarian reserve markers, focusing on anti-Müllerian hormone (AMH) and basal FSH (bFSH). Logistic regression assessed the association between specific element concentrations and POI occurrence, and the posterior inclusion probability model tested the robustness of key driving factors. The study identified 24 trace elements in follicular fluid samples, revealing significant differences in 23 elements between the two groups. There were positive correlations between Cu, I, Se, and Zn with AMH levels, while negative correlations were observed for Ca, Co, Li, and AMH. Nonlinear relationships were noted for Ba, Cd, Fe, Mg, Mn, Mo, and Pb. Ca, Li, and Ni showed a significant positive correlation with bFSH, while Cu, I, Mg, Se, and Zn demonstrated a significant negative correlation with bFSH. Additionally, Ba, Mn, and Pb exhibited a nonlinear correlation with bFSH. Individuals in the medium and high tertiles for Cu, I, Pb, Se, and Zn were less likely to develop POI. In contrast, those in the medium and high tertiles for Ba, Ca, Cd, Li, Mn, and Ni had an increased likelihood of POI. Our study addresses a crucial gap by examining trace element exposure in follicular fluid and its link to POI risk, enhancing understanding of their effects on female ovarian function. This study lays a foundation for monitoring female fertility and emphasizes the importance of environmental pollutants on reproductive health.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"135 ","pages":"Article 108947"},"PeriodicalIF":3.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu Zhou , Yifan Hong , Shengwen Wang , Luna He , Yan Cui , Yinghua Wu , Fuli Yan , Chunlan Long , Jing Gao
{"title":"Impact of the environmental endocrine disruptor flutamide on cryptorchidism: Molecular mechanisms involving connexin-43 and p38-MAPK signaling","authors":"Yu Zhou , Yifan Hong , Shengwen Wang , Luna He , Yan Cui , Yinghua Wu , Fuli Yan , Chunlan Long , Jing Gao","doi":"10.1016/j.reprotox.2025.108945","DOIUrl":"10.1016/j.reprotox.2025.108945","url":null,"abstract":"<div><div>Cryptorchidism, a condition associated with male infertility, is exacerbated by exposure to environmental endocrine disruptors such as flutamide. This study investigates the molecular mechanisms of cryptorchidism and potential interventions targeting endocrine disruptor-induced testicular damage. A rat model of congenital cryptorchidism was established via prenatal flutamide exposure, and testes were harvested at postnatal day 90. Testicular histology, transcriptome sequencing, bioinformatic analysis, sperm analysis, immunohistochemistry, and lentiviral vector transfection were conducted. Cryptorchid testes exhibited impaired seminiferous tubule development, significant reductions in sperm count, and increased sperm abnormalities. Tight and gap junction proteins essential for blood-testis barrier (BTB) integrity, including Claudin-11, Occludin, and Connexin-43, were markedly downregulated. Transcriptomic analysis revealed activation of the p38 MAPK signaling pathway and excessive apoptosis in cryptorchid testes. Overexpression of Connexin-43 restored BTB integrity and suppressed the p38 MAPK pathway, rescuing spermatogenesis. These findings underscore the role of environmental anti-androgens in cryptorchidism pathogenesis and highlight Connexin-43 as a potential therapeutic target for mitigating testicular damage caused by endocrine disruptors.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"135 ","pages":"Article 108945"},"PeriodicalIF":3.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Plasticizer exposure and reproductive dysfunction: Assessing bisphenol A and phthalate esters impact on ovarian reserve in women with PCOS-associated infertility","authors":"Jalpa Patel , Hiral Chaudhary , Sonal Panchal , Rushikesh Joshi","doi":"10.1016/j.reprotox.2025.108949","DOIUrl":"10.1016/j.reprotox.2025.108949","url":null,"abstract":"<div><div>Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder among women of reproductive age, frequently causing infertility. This study investigates the influence of endocrine-disrupting chemicals (EDCs) on ovarian reserve parameters in women with PCOS-related infertility. A cohort of 61 women with PCOS, aged 29.90 ± 3.64 years, was recruited from Dr. Nagori’s Institute for Infertility in Ahmedabad, Gujarat. Serum levels of Bisphenol A (BPA), Mono-ethylhexyl phthalate (MEHP), and Di-ethylhexyl phthalate (DEHP) were measured using high-performance liquid chromatography (HPLC). Ovarian reserve markers were assessed, including antral follicle count (AFC) and anti-Müllerian hormone (AMH) levels. Hormonal profiles and metabolic parameters were also analyzed. Correlations between EDCs and ovarian reserve markers were evaluated using Pearson correlation and regression analyses. The study found serum mean levels of BPA (77.80 ± 51.82 ng/ml), MEHP (37.43 ± 19.85 μg/ml), and DEHP (5.77 ± 7.21 μg/ml). Participants exhibited typical PCOS hormonal profiles with elevated testosterone and AMH levels, and significant insulin resistance was observed. Correlation analysis showed a positive relationship between AMH levels and AFC (r = 0.47, p = 0.01). However, no significant associations were found between EDC exposure and ovarian reserve markers. A high prevalence of adenomyosis and bilateral polycystic ovaries was noted among the participants. While metabolic and hormonal disruptions are prominent in PCOS, the direct impact of EDCs on ovarian reserve parameters appears minimal. This study highlights the necessity of addressing metabolic health and environmental exposures in managing PCOS related infertility to improve reproductive outcomes.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"135 ","pages":"Article 108949"},"PeriodicalIF":3.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah Munk Andreasen , Lars Christian Lund , Casper P. Hagen , Margit Bistrup Fischer , David Møbjerg Kristensen , Anders Juul , Gylli Mola , Hanne Frederiksen , Tina Kold Jensen
{"title":"Maternal urinary paracetamol concentrations and self-reported paracetamol use in mid-gestation: Association to reduced anogenital distance in Offspring from infancy to 9 years","authors":"Sarah Munk Andreasen , Lars Christian Lund , Casper P. Hagen , Margit Bistrup Fischer , David Møbjerg Kristensen , Anders Juul , Gylli Mola , Hanne Frederiksen , Tina Kold Jensen","doi":"10.1016/j.reprotox.2025.108946","DOIUrl":"10.1016/j.reprotox.2025.108946","url":null,"abstract":"<div><div>Studies have found associations between self-reported paracetamol use during pregnancy and shorter anogenital distance (AGD) in male infants, suggesting paracetamol have antiandrogenic properties. We investigated whether self-reported paracetamol use or quantified paracetamol concentration in maternal urine was associated with AGD in offspring from infancy to 9 years. In the Odense Child Cohort, women completed three questionnaires about paracetamol use during pregnancy and provided urine samples around GW28. AGDs were assessed in offspring at 3, 18 months, 3, 5, 7 and 9 years. Maternal self-reported paracetamol use was available for 931 boys and 793 girls with 6292 AGD measurements. Maternal urine concentrations were available for 281 boys and 233 girls with 2298 AGD measurements. Associations were analysed using propensity score-weighted linear regression adjusted for child height. 65 % of women reported using paracetamol during pregnancy. Detectable paracetamol was found in all participants, with 6 % (>4000 ng/ml) indicating recent use. Paracetamol concentrations indicating recent use were non-significantly associated with −1.71 % and −2.25 % shorter AGD in boys and girls. Self-reported paracetamol use anytime during pregnancy was significantly associated with −1.56 % shorter AGD in girls. Use before GW14 and between GW15-29 was non-significantly associated with −1.71 % and −1.79 % shorter AGD in boys, while use between GW15-29 and after GW30 was significantly associated with −2.52 % and −2.72 % shorter AGD in girls. The observed AGD changes were modest with little impact for the individual. However, as 65 % of pregnant women used paracetamol, these findings raise public health concerns given the increasing prevalence of reproductive disorders.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"135 ","pages":"Article 108946"},"PeriodicalIF":3.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanistic decoding of octyl methoxycinnamate-induced breast toxicity via network toxicology, mendelian randomization, and molecular simulations","authors":"Yinghao Xiao, Jixin Li, Jiahui Xu, Mingyang Sheng, Zhidong Qiu, Wei Xu","doi":"10.1016/j.reprotox.2025.108943","DOIUrl":"10.1016/j.reprotox.2025.108943","url":null,"abstract":"<div><div>Octyl methoxycinnamate (OMC), a widely used UV filter, has raised concerns due to its potential reproductive toxicity and association with endocrine disruption. This study systematically identified OMC-induced breast toxicity targets and elucidated underlying molecular mechanisms by integrating network toxicology, differential gene expression analysis, Mendelian randomization (MR), molecular docking, and molecular dynamics (MD) simulations. Using SwissTargetPrediction, OMIM, GeneCards and DisGeNET databases, 185 potential targets linked to OMC exposure and breast injury were identified. STRING and Cytoscape analyses highlighted 31 hub targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment revealed significant associations with immune responses, cell proliferation, and signaling pathways. Analysis of GEO datasets identified overlapping differentially expressed genes (DEGs) between core targets and breast cancer (BC). MR analysis demonstrated a causal relationship between PTGS2 and BC risk. Molecular docking indicated strong binding affinities between OMC and core targets, particularly MMP9. MD simulations further confirmed stable OMC-PTGS2 interactions, supporting PTGS2 as a key mediator of OMC-induced breast toxicity. This work provides a theoretical foundation for understanding OMC’s breast toxicity mechanisms and lays groundwork for preventing or managing breast disorders in populations exposed to OMC-containing environments.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"135 ","pages":"Article 108943"},"PeriodicalIF":3.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Human organoids potentially boost research into environmental factors of neural tube defects","authors":"Huili Li, Jing Zhang, Lee Niswander","doi":"10.1016/j.reprotox.2025.108936","DOIUrl":"10.1016/j.reprotox.2025.108936","url":null,"abstract":"<div><div>Human neural tube closure occurs during the third to fourth gestational week, often before people realize they are pregnant. Ethical issues limit collection of embryonic human neural tube tissue. However, the development of human neural tube organoids is beginning to empower the study of neural tube closure and neural tube defects. A previous review summarized human neural tube organoid models which are grown on top of or embedded in Matrigel or Hydrogel. Recent advances in human neural tube organoid models through micropatterned or microfluidic methods recapitulate diverse and complex neural tube features. In this review, our goal is to summarize these human iPSC-derived advanced organoid models. Moreover, these organoid models provide the possibility of testing how environmental factors influence the process of neural tube closure. Focusing on folic acid supplementation which can reduce the prevalence of neural tube defects, we review experimental evidence for three molecular mechanisms of folic acid function. Our perspective is to boost research on the impacts of environmental factors on reducing the risk of neural tube defects by utilizing human neural tube organoid models.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"135 ","pages":"Article 108936"},"PeriodicalIF":3.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Editorial - Special issue on advances in craniofacial teratology.","authors":"Scott E Parnell, Johann K Eberhart","doi":"10.1016/j.reprotox.2025.108942","DOIUrl":"https://doi.org/10.1016/j.reprotox.2025.108942","url":null,"abstract":"","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"108942"},"PeriodicalIF":3.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Judith Wieloch , Jordi Blanco , Catrin Zordick , Nils Ohnesorge , Marlon R. Schneider , Marta Barenys , Fanny Knöspel
{"title":"In vitro embryolethality testing during the peri-implantation stage using 3D mouse embryoids: Comparison with 2D mouse cell cultures and the zebrafish embryo model","authors":"Judith Wieloch , Jordi Blanco , Catrin Zordick , Nils Ohnesorge , Marlon R. Schneider , Marta Barenys , Fanny Knöspel","doi":"10.1016/j.reprotox.2025.108941","DOIUrl":"10.1016/j.reprotox.2025.108941","url":null,"abstract":"<div><div>The recent development of <em>in vitro</em> embryoid models may be a way to reduce or even replace animals in developmental and reproductive toxicity (DART) studies. Here, we evaluated an <em>in vitro</em> mouse 3D embryoid model using three stem cell lineages including mouse embryonic stem cells (ESC), trophoblast stem cells (TSC) and extra-embryonic endoderm stem cells (XENC) to detect embryolethality of seven known positive or negative compounds at the peri-implantation stage <em>in vivo</em>. We performed a comparative study by testing these substances in parallel on monocultures of the individual cell lines in 2D and in zebrafish embryos. Embryoids were exposed to each compound for 48 h and analysed on day <em>in vitro</em> (DIV) 4, which resemble the peri-implantation embryo at E5.5 <em>in vivo</em>. Metabolic activity, morphological development and gene expression were evaluated. We showed that all early direct embryolethal compounds significantly reduced the metabolic activity of the embryoids at an <em>in vivo</em> relevant concentration range. Furthermore, this model could also detect embryolethal compounds that have specific adverse effects on extraembryonic structures. The additional endpoints (gene expression or morphological assessments) were required to detect adverse effects when only a minoritarian cell type of the embryoid was affected. In contrast, zebrafish embryos had a very low sensitivity, and the monocultures of the individual cell lines were less specific than the 3D embryoids. Combining 2D and 3D testing with carefully selected additional endpoints could serve as a powerful tool to assess the potential effects of new chemicals on embryo development at the peri-implantation stage.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"135 ","pages":"Article 108941"},"PeriodicalIF":3.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}