Reproductive toxicology最新文献

{"title":"Use of the alternative test R-FETAX (Refined-Frog Embryo Teratogenicity Assay-Xenopus) to evaluate the Fetal Alcohol Spectrum Disorders (FASD)","authors":"M. Battistoni ,&nbsp;F. Di Renzo ,&nbsp;F. Metruccio ,&nbsp;R. Bacchetta ,&nbsp;E. Menegola","doi":"10.1016/j.reprotox.2025.108896","DOIUrl":"10.1016/j.reprotox.2025.108896","url":null,"abstract":"<div><div>Fetal Alcohol Spectrum Disorders (FASD) refer to a range of conditions in children caused by alcohol consumption during pregnancy, including morphological defects, developmental delays, and neurobehavioral impairments. Ethanol (EtOH) at high concentrations (1–3 % v/v) was shown to induce malformations and lethality in <em>Xenopus laevis</em> embryos exposed throughout the FETAX test (from the mid-blastula stage to the final pre-feeding larval stage). The aim of this work was to evaluate multiple morphological and neurobehavioral effects of EtOH exposure (0.1–3 % v/v) using the R-FETAX protocol. Embryos obtained through natural mating were exposed during specific developmental windows: the organogenetic period (sensitive to morphological abnormalities) and the neurodevelopmental window (sensitive to behavioral alterations). Additional groups were exposed either throughout the entire test duration (classical FETAX exposure) or for a brief 4-hour period before the end of the test (acute exposure). Lethality was monitored over the six-day test period. At the conclusion of the test, a functional deglutition test was performed, and external gross morphology as well as developmental delays (FETAX-score method) were assessed. Neurobehavioral swimming test was conducted only on tadpoles considered normal at gross morphological evaluation. Dose-response relationships were modeled using PROAST software to derive benchmark dose levels, with response set at levels used as points of departure for risk assessment. The findings demonstrated dose- and stage-specific effects that mimic FASD symptoms observed in humans. These results emphasize that no amount of alcohol exposure can be considered safe during development.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"134 ","pages":"Article 108896"},"PeriodicalIF":3.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143644161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zebrafish embryos as a teratogenicity screening tool to reduce potential birth defects.","authors":"Zongyu Miao, Jing Yang, Lei Cai, Zhenlie Huang, Erping Yan, Jinghui Peng, Xueping Chen, Jinping Cheng","doi":"10.1016/j.reprotox.2025.108895","DOIUrl":"https://doi.org/10.1016/j.reprotox.2025.108895","url":null,"abstract":"<p><p>Teratogens play a crucial role in the development of birth defects, making effective screening vital for prevention and management. This study aimed to develop an optimized zebrafish embryo-based platform for teratogenicity screening and further evaluate its findings with established clinical and animal data. Zebrafish embryos [6-8hours post-fertilization (hpf)] were exposed to 19 different test solutions, including nine known teratogens and ten non-teratogens, in 96-well plates, and mortality and morphological abnormalities were assessed at 48, 72, and 96 hpf. The half-lethal concentration (LC₅₀) and half-effective concentration (EC₅₀) were calculated from the counts of dead and abnormal embryos, respectively. The teratogenicity index (TI), defined as LC₅₀ / EC₅₀, was used to classify the chemicals. Of the tested compounds, eight were identified as teratogenic, nine as non-teratogenic, and two outliers due to solubility constraints in this assessment. Notably, extending the exposure duration to 96 hpf provided a more accurate assessment of teratogenicity compared to shorter exposures. Eight teratogenic substances exhibited a TI greater than 3, while (-)-thalidomide did not yield a definitive TI due to low solubility. Among the non-teratogenic chemicals, nine had a TI below 3, with ajmaline also lacking a precise TI due to solubility constraints. These findings suggest that using a 6-8 hpf to 96 hpf exposure window and establishing a TI threshold of 3 can facilitate reliable teratogenicity risk assessment. Furthermore, the phenotypes observed in zebrafish embryos were consistent with typical teratogenic malformations documented in clinical and animal studies. This study demonstrates that the refined zebrafish embryo teratogenicity testing method coupled with the TI, can be an effective tool for assessing teratogenic risk.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"108895"},"PeriodicalIF":3.3,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650101","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":"Bisphenol AF induces cell cycle arrest and apoptosis in TM3 Leydig cells via the p53 signaling pathway.","authors":"Chenlu Li, Haolong Luo, Mengyuan Chen, Fuxing Lin, Xiangmei Ren, Yefei Huang, Li Zhou","doi":"10.1016/j.reprotox.2025.108882","DOIUrl":"https://doi.org/10.1016/j.reprotox.2025.108882","url":null,"abstract":"<p><p>Bisphenol AF (BPAF), one of the most common bisphenol analogues, has been reported to exhibit higher estrogenic activity compared to bisphenol A (BPA) due to the presence of additional hydrophobic groups. To comprehensively understand the male reproductive toxicity of BPAF, TM3 Leydig cells were used to investigate the effects of BPAF on cell proliferation, apoptosis, and cell cycle arrest. The underlying mechanisms of cellular responses induced by BPAF were examined through analysis of target mRNA and protein expression. Results showed that BPAF treatment reduced cell viability and induced both G2/M cell cycle arrest and apoptosis in a time- and dose-dependent manner in TM3 Leydig cells. RNA sequencing analysis and experimental verification further revealed that the p53 signaling pathway was involved in BPAF-induced cytotoxicity. Furthermore, Pifithrin-α (PFT-α), a p53 inhibitor, attenuated BPAF-induced G2/M cell cycle arrest and apoptosis. These results demonstrate that the p53 signaling pathway mediates BPAF-induced cell cycle arrest and apoptosis in Leydig cells, providing mechanistric insights into BPAF's toxicological effects on the male reproductive system.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"108882"},"PeriodicalIF":3.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634572","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":"1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal exposure induces testicular toxicity in male mice","authors":"Huage Liu","doi":"10.1016/j.reprotox.2025.108881","DOIUrl":"10.1016/j.reprotox.2025.108881","url":null,"abstract":"<div><div>Thirdhand smoke (THS), a residual cigarette smoke still remaining in indoor environment long after active smoking has ceased, has aroused more and more people’s attention on health. However, the impact of THS exposure on the male reproductive system, particularly in in-vivo study, remain unclear. Thus, this study aims to investigate the adverse effects of 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal (NNA), a special component in THS, on testis. Herein, adult ICR mice were orally administered diluted dimethylsulfoxide (control), 0.075 μg/kg and 0.15 μg/kg NNA for 10 weeks. The findings revealed that NNA exposure, especially in 0.15 μg/kg dosage, significantly reduced the epithelium height and tubular area within the testis. Transcriptomic analysis indicated that NNA exposure interfered with the expression of genes associated with oxygen transport and oxygen binding processes, such as <em>Hbb-bs</em>, the downregulation of which also led to oxidative damage. Additionally, NNA exposure induced oxidative damage in testis by decreased levels of SOD and GSH enzymes, along with an increase in MDA level. In summary, our results demonstrate that NNA exposure causes impaired testicular structure and oxidative damage, indicating its testicular toxicity. This finding not only implies the detrimental effect of NNA on male reproduction, but also provides a fundamental basis for further research on the impact of THS exposure on male reproductive health.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"133 ","pages":"Article 108881"},"PeriodicalIF":3.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143561876","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":"Low-level exposure to environmental lithium element affects male reproductive outcomes: Results from the MARHCS cohort study in Chongqing, China and in vivo animal experiments","authors":"Lihong Wang ,&nbsp;Guanghui Zhang ,&nbsp;Xi Ling ,&nbsp;Mei Wan ,&nbsp;Qing Chen ,&nbsp;Lei Sun ,&nbsp;Huan Yang ,&nbsp;Tong Wang ,&nbsp;Jinyi Liu ,&nbsp;Jia Cao ,&nbsp;Lin Ao ,&nbsp;Peng Zou","doi":"10.1016/j.reprotox.2025.108875","DOIUrl":"10.1016/j.reprotox.2025.108875","url":null,"abstract":"<div><div>This study examined the effects of lithium exposure at environmental levels on semen quality and sex hormone levels. Questionnaires and biological samples were collected from 582 college students recruited in Chongqing, China. Sex hormones and semen parameters were measured by ELISA and CASA, respectively. Sperm telomere length and mitochondrial DNA copy number were determined using real-time Q-PCR. Lithium levels were quantified by ICP-MS. In addition, C57BL/6 mice were administered lithium chloride at doses within the range of environmental levels (LiCl; 0, 4.3, 12.8, and 38.4 mg/kg) for 35 days, and the expression of key proteins involved in testosterone synthesis was detected by western blot assay. In the population study, the median lithium levels in urine and seminal plasma were 18.80 and 5.38 μg/L, respectively. Each interquartile range increase of lithium levels in both urine and seminal plasma were associated with decreased serum testosterone (−2.47 %, 95 % CI: −4.52 %, −0.38 % for urine; −2.67 %, 95 % CI: −4.79 %, −0.50 % for seminal plasma) and progesterone (−6.38 %, 95 % CI: −11.09 %, −1.42 % for urine; −8.78 %, 95 % CI: −13.20 %, −4.04 % for seminal plasma). Mice treated with the highest LiCl dose (38.4 mg/kg) had significantly lower sperm motility, sperm concentration, and testosterone, progesterone, estradiol, and prolactin levels than mice in the control group (all <em>p</em> &lt; 0.05), and their Leydig cells showed marked mitochondrial vacuolation and swelling. These results support that environmental lithium exposure leads to decreased semen quality and testosterone by impairing Leydig cells.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"134 ","pages":"Article 108875"},"PeriodicalIF":3.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573847","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":"Developmental and reproductive toxicity (DART) study of a novel SARS-CoV-2 tetravalent recombinant protein vaccine (SCTV01E) in rats","authors":"Xiao Zhang ,&nbsp;Jilei Jia ,&nbsp;Gaojian Chen ,&nbsp;Dan Meng ,&nbsp;Juan Ma ,&nbsp;Huimin Wang ,&nbsp;Shaozheng Zhou ,&nbsp;Lin Ma ,&nbsp;Qianqian Qian ,&nbsp;Xuejie Liu ,&nbsp;Xuefeng Li ,&nbsp;Liangzhi Xie","doi":"10.1016/j.reprotox.2025.108878","DOIUrl":"10.1016/j.reprotox.2025.108878","url":null,"abstract":"<div><div>SCTV01E, a novel SARS-CoV-2 tetravalent protein vaccine containing recombinant spike proteins of Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2) and Omicron BA.1 (B.1.1.529.1) variants and SCTVA02B adjuvant, has received Emergency Use Authorization (EUA) in China and the United Arab Emirates (UAE) as a next-generation COVID-19 vaccine. A comprehensive reproductive and developmental toxicity evaluation was conducted in Sprague-Dawley (SD) rats under Good Laboratory Practice (GLP) conditions. Maternal animals were intramuscularly injected with 1 × or 3 × the highest human dose every other week prior to mating, followed by booster immunizations during gestation and lactation periods. The main findings showed that SCTV01E vaccination elicited robust binding IgG and neutralizing antibody responses against all four target variants. While no vaccine-related adverse reproductive effects were observed in parental male or female rats, transient injection site reactions and slight, reversible reductions in body weight gain and food consumption were noted. Key developmental parameters were not affected, and postnatal evaluation revealed no evidence of embryo-fetal malformations, developmental delays, or functional impairments in offspring. These results suggest a favorable safety profile for SCTV01E and its possible suitability for clinical trials in humans of reproductive potential. Furthermore, the efficient transplacental and lactational transfer of maternal antibodies observed in animal models suggests a potential protection: direct immunization of mothers may confer passive immunity to both fetuses in utero and neonates during breastfeeding.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"134 ","pages":"Article 108878"},"PeriodicalIF":3.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subcutaneous zilucoplan: Evaluation of reproductive toxicology","authors":"Marie Lemper ,&nbsp;C. Marc Luetjens ,&nbsp;Antje Fuchs ,&nbsp;Peter Hall ,&nbsp;François-Xavier Mathy ,&nbsp;Jeff Long ,&nbsp;Joy Cavagnaro ,&nbsp;Sucharita Roy ,&nbsp;Evan A. Thackaberry ,&nbsp;Petra Duda","doi":"10.1016/j.reprotox.2025.108877","DOIUrl":"10.1016/j.reprotox.2025.108877","url":null,"abstract":"<div><div>To further understand the safety profile of zilucoplan, reproductive toxicology studies in non-human primates (NHPs) were performed, including a male fertility study and a combined embryo–foetal development (EFD) and enhanced pre- and postnatal development (ePPND) study. Human transplacental transfer of zilucoplan was examined in an <em>ex vivo</em> human placental perfusion model of foetal exposure during pregnancy. By comparison with the positive control, a low transfer rate of 0.5 % was observed with a target blood zilucoplan concentration that mimics the therapeutic dose of 0.3 mg/kg used in clinical trials in patients with generalised myasthenia gravis. In each <em>in vivo</em> study, daily subcutaneous zilucoplan 1.0, 2.0 or 4.0 mg/kg or vehicle control were randomly assigned. Six male cynomolgus monkeys/group received treatment for 13 weeks (male fertility), 4 females/group received treatment for 80 days (EFD) and 16 females/group received treatment from gestation day 20 to delivery (∼140 days, ePPND). Developmental, reproductive and toxicokinetic effects were analysed. No zilucoplan-related reproductive effects were observed in the male fertility study. There were no effects on pregnancy outcome, number of viable foetuses or foetal development in the combined EFD/ePPND study. Overall pregnancy loss (including stillbirths and death during birth) was 25.0 % (4/16) in the control group compared with 37.5 % (6/16) in the zilucoplan-treated groups and was within the published range of pregnancy loss in cynomolgus monkeys. These reproductive toxicity studies demonstrate no adverse effect of zilucoplan on male fertility or maternal or embryo–foetal outcomes, and no pre- or postnatal toxicity in NHPs receiving daily zilucoplan. Data from the <em>ex vivo</em> placental transfer model and the lack of effect of FcRn-mediated transfer on zilucoplan suggest that placental transfer is low.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"134 ","pages":"Article 108877"},"PeriodicalIF":3.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Propylparaben negatively impacts IN VITRO preimplantation mouse embryo development","authors":"Nastasia Z.E. Lai ,&nbsp;Shah Tauseef Bashir ,&nbsp;Ayelet Ziv-Gal ,&nbsp;Mayandi Sivagaru ,&nbsp;Romana A. Nowak","doi":"10.1016/j.reprotox.2025.108876","DOIUrl":"10.1016/j.reprotox.2025.108876","url":null,"abstract":"<div><div>Parabens are chemicals widely used in personal care products and food as antimicrobial preservatives. They exhibit potential estrogenic activity by binding to estrogen receptors 1 and 2, classifying them as endocrine-disrupting chemicals. Given the substantial daily exposure of women to parabens, it is crucial to investigate their effects on the female reproductive system. Previous studies in mouse models have shown that paraben exposure impacts ovarian development, resulting in an increase in cystic follicles and a decrease in corpora lutea. However, the effects of parabens on embryo development have not been extensively studied. This study aimed to determine the impact of propylparaben exposure on preimplantation embryo development <em>in vitro</em>. We tested the effects of 0 (0.075 % DMSO), 0.5 μg/mL, 5.0 μg/mL, 10 μg/mL, and 15 μg/mL propylparaben on rate of development of mouse zygotes to hatched blastocyst stage, quantified the number of inner cell mass (ICM) and trophectoderm (TE) cells in hatched blastocysts, and the distribution of cytoskeletal F-actin. The percentage of hatched blastocysts was significantly decreased at 0.5 μg/mL and 10 μg/mL compared to controls. Propylparaben treatment did not alter TE cell numbers. However, treatment with 0.5 or 15 μg/mL significantly decreased the number of ICM cells compared to controls. Additionally, the intensity of phalloidin fluorescence staining for F-actin was significantly reduced at 10 μg/mL and 15 μg/mL propylparaben. In summary, our findings show that propylparaben exposure disrupts ICM formation, impacts the cytoskeletal filamentous actin (F-actin) network, and alters the rate of hatched blastocyst development in preimplantation mouse embryos.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"133 ","pages":"Article 108876"},"PeriodicalIF":3.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548555","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":"Effect of 1-nitropyrene exposure on the biological behavior of trophoblast cells","authors":"Chuting Wang ,&nbsp;Long Zhang ,&nbsp;Daidi Gui ,&nbsp;Wenjing Zou ,&nbsp;Menglei Zhu ,&nbsp;Yu Liu ,&nbsp;Lei Hua ,&nbsp;Changlian Li ,&nbsp;Rui Ding","doi":"10.1016/j.reprotox.2025.108865","DOIUrl":"10.1016/j.reprotox.2025.108865","url":null,"abstract":"<div><div>1-nitropyrene (1-NP) is a toxic component of PM_2.5 that adversely affects human health, especially pregnant women; however, the mechanisms are still unclear. This study aims to explore the mechanisms by which 1-NP influences trophoblast cell behaviors. HTR8/Svneo cells were treated by different concentrations of 1-NP (0, 5, 10, 20 μM) to assess clonogenic, invasive, and migratory abilities. Western blot analysis was used to assess the expression of EMT and Wnt/β-catenin pathway proteins. 1-NP significantly inhibited HTR8/Svneo cell clonogenic ability, especially at 10 μM and 20 μM (<em>P</em> &lt; 0.01). Invasiveness decreased by 68.44 % at 5 μM (<em>P</em> &lt; 0.05), and migration was significantly inhibited at 10 μM and 20 μM (<em>P</em> &lt; 0.05). Western blot revealed increased E-cadherin and decreased Vimentin (<em>P</em> &lt; 0.01), elevated β-catenin (<em>P</em> &lt; 0.05), and reduced APC (<em>P</em> &lt; 0.01). In summary, 1-NP impacts trophoblast cell clonogenicity, invasion, and migration by modulating EMT and Wnt/β-catenin pathways, providing novel insights into its biological effects on trophoblast cells.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"133 ","pages":"Article 108865"},"PeriodicalIF":3.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534070","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":"Associations between urinary and follicular fluid concentrations of phthalate metabolites and reproductive outcomes in Brazilian women undergoing fertility treatment","authors":"Carla Giovana Basso ,&nbsp;Bruno Alves Rocha ,&nbsp;Ivana Rippel Hauer ,&nbsp;Jonas Carneiro Cruz ,&nbsp;Francisco Furtado Filho ,&nbsp;Fernando Barbosa Jr ,&nbsp;Anderson Joel Martino-Andrade","doi":"10.1016/j.reprotox.2025.108868","DOIUrl":"10.1016/j.reprotox.2025.108868","url":null,"abstract":"<div><div>Existing literature indicates that phthalates can be toxic to the ovaries, negatively affecting female reproduction and potentially influencing outcomes in assisted reproductive technology (ART). However, data on associations between urinary and/or follicular fluid phthalate concentrations and ART outcomes in South American women are scarce. Therefore, in this prospective study, we recruited 93 women (n = 119 cycles) undergoing ART at a fertility clinic in Brazil. They provided urine and follicular fluid (FF) samples, from which we measured the concentrations of the 15 phthalate metabolites more frequently found in Brazilian populations. We documented both laboratorial and clinical outcomes, estimating associations using negative binomial regression. Our findings revealed that specific oocyte and embryo development parameters were associated with urinary concentrations of phthalate metabolite. Particularly, number of follicles, maturation, as well as blastulation were negatively associated with Mono-benzyl phthalate (MBzP). Similarly, urinary mono-ethyl phthalate (MEP) was associated with lower rates of maturation, good quality and blastulation. However, some parameters positively associated with mono-(carboxyisooctyl) phthalate (MCiOP), including maturation, good quality, and blastulation. We also observed certain associations between embryo development and FF concentrations of phthalate metabolite, although the magnitude and direction of these associations differed among various metabolites. Overall, our results suggest that urinary and FF concentrations of phthalate metabolite may be linked to altered outcomes in ART cycles. However, further studies are needed to clarify the extent of this impact. Our results support previous literature and is the first to evaluate urinary and FF phthalate metabolites concentrations in South American women undergoing infertility treatment.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"133 ","pages":"Article 108868"},"PeriodicalIF":3.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537414","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}