Reproductive toxicology最新文献

{"title":"Subchronic exposure to Voliam Targo® affects ovarian histology and reproductive performance in rabbits (Oryctolagus cuniculus).","authors":"Thiziri Tlili ,&nbsp;Hassina Khaldoun ,&nbsp;Nacira Zerrouki Daoudi ,&nbsp;Rebiha AROUN ,&nbsp;Chahrazed Makhlouf ,&nbsp;Amina Settar ,&nbsp;Liza Benamara ,&nbsp;Nacima Djennane ,&nbsp;Smail Krabi","doi":"10.1016/j.reprotox.2025.109015","DOIUrl":"10.1016/j.reprotox.2025.109015","url":null,"abstract":"<div><div>In the current study, we evaluated the subchronic toxic effects of the Voliam Targo® (VT) insecticide on the ovaries of rabbits (<em>Oryctolagus cuniculus</em>) as well as the potential reproductive performance effects. The experiment was conducted using thirty females and thirty males, which were divided into two treated groups: control (distilled water) and VT (15 mg/kg b.w., by gavage, daily for 85 days). After a treatment period of 17 days, male and female rabbits from the two groups were randomly assigned to four artificial insemination (AI) mating groups using heterospermy or homospermy. The regimen continued through the gestation periods until 35 days of lactation, during which the first-generation (F1) offspring were monitored. At the end of the study, histomorphometric and immunohistochemical analyses were used to assess ovarian damage. The results revealed that body, ovary, uterine horn, cervix, and vagina weights did not vary significantly in the VT group compared to the control. Concerning reproductive performance, paternal exposure to VT insecticide caused a significant (p &lt; 0.01) increase in the number of live fetuses and a decrease in the percentage of death in pups during the postnatal period. Also, VT treatment resulted in ovarian tissue structure disorganization, including follicular atresia, hemorrhagic follicles, and ovarian degeneration. Moreover, Ki67, P53, and Bcl-2 protein expression in the ovaries of the VT-treated group differed from the control group. This study suggests that subchronic exposure to Voliam Targo® may affect ovarian structure and reproductive performance by altering cell proliferation and apoptosis.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109015"},"PeriodicalIF":2.8,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721814","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":"Reprotoxic effect of bisphenol F and bisphenol S on female Drosophila melanogaster exposed during development","authors":"Elize Musachio ,&nbsp;Bianca Munieweg da Silva ,&nbsp;Graziela Moro Meira ,&nbsp;Barbara Osmarin Turra ,&nbsp;Cibele Ferreira Teixeira ,&nbsp;Fernanda Barbisan ,&nbsp;Luana Barreto Meichtry ,&nbsp;Eliana Jardim Fernandes ,&nbsp;Dieniffer Espinosa Janner ,&nbsp;Gustavo Petri Guerra ,&nbsp;Marina Prigol","doi":"10.1016/j.reprotox.2025.109017","DOIUrl":"10.1016/j.reprotox.2025.109017","url":null,"abstract":"<div><div>What is the effect of exposure to Bisphenol F (BPF) and Bisphenol S (BPS) during the embryonic and developmental period on the reproductive system of filial generation 1 (F1) female flies? To answer this question, <em>Drosophila melanogaster</em> were used, which remained throughout the development period, at different concentrations of BPF and BPS (0.25, 0.5, and 1 mM, separately). Upon hatching, evaluation of wing size and body weight, in addition to the expression of the ecdysone receptor (EcR) and enzymes catalase (CAT) and superoxide dismutase (SOD), quantification of reactive species (RS) and CYP 450 activity were performed in part of virgin females (F1). Another part of the females (F1) were mated with untreated males to assess reprotoxicity through tests such as fertility and fecundity, by counting the number of eggs laid and hatched, and evaluation of ovary morphology and viability of ovarian cells. Exposure to 1 mM BPF, 0.5 and 1 mM BPS reduced the ability of flies to lay eggs, changed the shape and size of the ovaries, reduced the viability of ovarian cells, increased body weight, and reduced wing size. EcR reduction was observed at all concentrations, accompanied by an increase of CAT and SOD expression and an increase in CYP450 activity. Even with increases in antioxidant enzymes, the reproductive system of females exposed to 1 mM BPF, 0.5 and 1 mM BPS may have succumbed to the rise in RS and reduction of EcR, which indicates endocrine dysregulation, thus manifesting a reprotoxic effect, highlighting BPS as more harmful.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109017"},"PeriodicalIF":2.8,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724894","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":"Folate deficiency mediates ovarian dysfunction through appetite and inflammatory pathways","authors":"Afridi Shaikh ,&nbsp;Bharti Choudhary ,&nbsp;Mukund Chhatpar ,&nbsp;Dewaunshi Panchakshari ,&nbsp;Dhaval Fefar ,&nbsp;Hetal Roy","doi":"10.1016/j.reprotox.2025.109016","DOIUrl":"10.1016/j.reprotox.2025.109016","url":null,"abstract":"<div><div>The long-established link between nutrition and reproduction is known to have critical consequences for reproductive function. However, the available experimental data on the effects of folate deficiency on ovarian health remains scarce. It is still unclear whether folate deficiency is directly responsible for causing ovarian-dysfunction and, if so, what are the underlying mechanisms. Therefore, our objective was to establish evidence for association between folate deficiency, hormone dynamics, and ovarian function using in vivo model. Folate-deprived female zebrafish were developed using intraperitoneal administration of methotrexate (MTX; DHFR inhibitor) and were used to study the possible implications of folate deprivation on ovarian health. Changes in the expression of transcripts regulating appetite and ovarian function was observed. We observed that folate deprivation resulted in impaired appetite behaviour and alteration in its regulatory gene expression. Due to folate deficiency, the neuroendocrine function of the brain was affected that resulted in altered reproductive hormone levels. Histology of ovary shows follicles arrested in primary oocyte stage and scarring of tissue is seen. Furthermore, elevated lipid peroxidation and catalase enzyme activity along with increased IL-6, indicates folate deficiency induced oxidative stress and inflammation in ovary as one of the possible mechanisms to aid- ovarian dysfunction. Our study provides experimental evidence, using an in vivo folate-deficient fish model, that underscores the essential role of folate in maintaining reproductive health. The intricate relationship between folate deficiency, appetite regulation, and its impact on the synthesis and release of female reproductive hormones calls for deeper investigation, particularly through studies involving mammalian models.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109016"},"PeriodicalIF":2.8,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724905","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":"The consumption of monosodium glutamate during the periconceptional period can impair preimplantation embryo development","authors":"Zuzana Šefčíková,&nbsp;Alexandra Špirková,&nbsp;Veronika Kovaříková,&nbsp;Laura Rušinová,&nbsp;Vladimír Baran,&nbsp;Jozef Pisko,&nbsp;Janka Babeľová,&nbsp;Dušan Fabian,&nbsp;Štefan Čikoš","doi":"10.1016/j.reprotox.2025.109014","DOIUrl":"10.1016/j.reprotox.2025.109014","url":null,"abstract":"<div><div>Monosodium glutamate (MSG) is one of the most commonly used food additives and is consumed worldwide as part of commercially processed foods. To study the possible reproductive risks of consuming monosodium glutamate during the periconceptional period (comprising oocyte maturation and the earliest stages of embryo development), we administered MSG (at doses of 500, 200 or 50 mg/kg body weight, by oral gavage) to female mice in this period. Preimplantation embryos were then isolated at D4 of gestation and analyzed. In blastocysts developed from female mice fed with MSG, we found a reduced proportion of blastocysts, a lower number of cells, and an increased proportion of dead cells. The expression of the proapoptotic gene Bak1 and active caspase-3 were significantly increased and telomeres were shorter in blastocysts isolated from MSG-fed females. The results of our previous in vitro study revealed that glutamate receptors are involved in the negative effects of glutamate on mouse blastocysts. In silico analysis of RNA-seq datasets containing data from human preimplantation embryos performed in this study revealed that NMDA receptors (formed from the GRIN2D or GRIN2B and GRIN3B subunits) and the GRM4 and GRM8 metabotropic receptors are expressed in human blastocysts. These results indicate that glutamate receptors could mediate the effects of MSG in human blastocyst cells. In summary, our results show that oral intake of relatively low doses of MSG during the periconception period can adversely affect early embryonic development and embryo quality and may pose a risk to successful conception and subsequent embryo development.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109014"},"PeriodicalIF":2.8,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725061","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":"Investigating the protective role of Astragalus polysaccharides against fluoride-induced testicular injury via network pharmacology, molecular docking, and in vivo experiments","authors":"Yue Pan ,&nbsp;Xingyan Du ,&nbsp;Yuanyuan Xiao ,&nbsp;Qiuhan Pi ,&nbsp;Yu Chen ,&nbsp;Jiajun Huang ,&nbsp;Didong Lou ,&nbsp;Wenchao Tang","doi":"10.1016/j.reprotox.2025.109012","DOIUrl":"10.1016/j.reprotox.2025.109012","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to investigate the protective effects of Astragalus polysaccharides (APS) against sodium fluoride (NaF)-induced testicular damage and to provide a theoretical basis for developing natural strategies to mitigate fluoride-induced reproductive toxicity.</div></div><div><h3>Methods</h3><div>Network pharmacology was employed to identify potential targets and pathways of APS in treating fluoride-induced testicular injury. Molecular docking was used to assess the binding affinity between APS active compounds and core targets. An in vivo rat model was established to evaluate testicular index, fluoride accumulation, and histopathological changes. Oxidative stress markers including SOD, CAT, GSH, and MDA were measured. Immunohistochemistry was performed to assess blood–testis barrier integrity and the expression of key targets (AKT1, ESR1, CASP3).</div></div><div><h3>Results</h3><div>Network pharmacology identified 34 potential APS targets, enriched in apoptosis, PI3K-Akt, and IL-1B signaling pathways. Molecular docking revealed strong binding affinity of APS components to core targets. APS significantly improved NaF-induced reductions in testicular index (<em>p</em> &lt; 0.01) and fluoride accumulation (<em>p</em> &lt; 0.05), alleviated seminiferous tubule atrophy and mitochondrial swelling, enhanced SOD, CAT activities and GSH levels (<em>p</em> &lt; 0.01), and reduced MDA levels (<em>p</em> &lt; 0.01). Moreover, APS upregulated CLDN1, ZO-1, and Occludin expression to repair the blood–testis barrier. Abnormal expression of AKT1, ESR1, CASP3, and HSP90AA1 was reversed by APS (<em>p</em> &lt; 0.01).</div></div><div><h3>Conclusion</h3><div>APS mitigates fluoride-induced testicular toxicity via multi-target regulation of oxidative stress and blood–testis barrier pathways, offering a novel therapeutic approach for fluoride-related reproductive damage.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109012"},"PeriodicalIF":3.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704164","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":"Late histopathological impacts on the female prostate of gerbils exposed to BPA during pregnancy and lactation.","authors":"Lorena Gabriela de Souza, Thalles Fernando Rocha Ruiz, Gervásio Evangelista Brito Filho, Luara Jesus Ferrato, Simone Jacovaci Colleta, Ellen Cristina Rivas Leonel, Sebastião Roberto Taboga","doi":"10.1016/j.reprotox.2025.109013","DOIUrl":"https://doi.org/10.1016/j.reprotox.2025.109013","url":null,"abstract":"<p><p>The female prostate is regulated by steroid hormones, mainly androgens and estrogens. Exposure to exogenous chemical compounds leads to effects via endocrine pathways that alter prostate morphophysiology. Bisphenol A (BPA) is a widespread endocrine disruptor, which influences estrogenic pathways, facilitating pre-neoplastic and neoplastic alterations in hormone-sensitive organs. The aim of this study was to evaluate the influence of BPA on the prostate of aged female gerbils exposed to the compound during their gestational and lactational periods. The females were exposed to 50μg/kg/daily during gestation and lactation, and the analysis was performed in the aged period (18-mo age). Our results showed that BPA increased epithelial alterations, observed by hyperplastic foci and a reduction in atrophies, commonly observed in aged female prostate. These data were supported by phopho-histone H3 immunostaining, that indicated proliferation of the epithelial and stromal compartments, leading to glandular hypertrophy. In addition, a pro-proliferative imbalance was observed through the differential expression of key proteins associated with cell death and proliferation, as well as in the expression of stromal components. Thus, the increase in cell proliferation implies the onset of epithelial alterations, as evidenced by the increased number of hyperplastic foci. The alterations reported after exposure to BPA demonstrated the increased likelihood of proliferative epithelial alterations, with tissue remodeling associated mainly with prostatic stroma.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109013"},"PeriodicalIF":2.8,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144733008","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":"Tattoo exposure and biomarkers of male fecundity: A cross-sectional study among young Danish males","authors":"Mette Møller Dornfeldt ,&nbsp;Sidsel Dan Hull ,&nbsp;Christel Nielsen ,&nbsp;Emelie Rietz Liljedahl ,&nbsp;Cecilia Høst Ramlau-Hansen ,&nbsp;Anne Gaml-Sørensen ,&nbsp;Gunnar Toft ,&nbsp;Jens Peter Bonde ,&nbsp;Karin Sørig Hougaard ,&nbsp;Sandra Søgaard Tøttenborg","doi":"10.1016/j.reprotox.2025.109009","DOIUrl":"10.1016/j.reprotox.2025.109009","url":null,"abstract":"<div><h3>Background</h3><div>Tattoo inks are mixtures of organic and inorganic color pigments and having a tattoo may be adversely associated with biomarkers of male fecundity.</div></div><div><h3>Objective</h3><div>To examine the association between tattoo exposure and biomarkers of male fecundity.</div></div><div><h3>Methods</h3><div>Participants were young adult Danish males (aged 18–21 years) sampled from the Danish National Birth Cohort. Upon recruitment in 2017–2019, participants answered a comprehensive questionnaire including information on tattoo exposure and provided a semen and blood sample. We applied a negative binomial regression model to estimate percentage differences (95 % confidence intervals [CI]) in semen characteristics, testicular volume, and reproductive hormone levels between tattooed and non-tattooed participants.</div></div><div><h3>Results</h3><div>Among the 1045 participants included in this study, 174 (17 %) had at least one tattoo and most tattooed participants (84 %) had tattoo(s) in only black color. About half (53 %) had one tattoo, 21 % had two tattoos, and 26 % had three or more tattoos. We observed no association between either number or color scheme of tattoo(s) relative to semen characteristics or reproductive hormone levels. Having a tattoo was associated with 6 % (95 % CI: 0, 12) larger testicular volume, but since testicular volume was measured by the participants themselves, this finding may be due to differential misclassification bias. Across all outcomes the crude and adjusted models were comparable.</div></div><div><h3>Conclusion</h3><div>Overall, we found no support for adverse associations between tattoo exposure and biomarkers of male fecundity, but studies with more details on tattoo exposure and longer follow-up of participants are needed before firm conclusions can be drawn.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109009"},"PeriodicalIF":2.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718261","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":"Oxidative stress: Oocyte quality and infertility","authors":"Ismat Ara Begum","doi":"10.1016/j.reprotox.2025.109011","DOIUrl":"10.1016/j.reprotox.2025.109011","url":null,"abstract":"<div><div>Infertility affects a significant proportion of couples worldwide, with female reproductive dysfunction contributing to nearly half of these cases. Oxidative Stress (OS), characterized by an imbalance between Reactive Oxygen Species (ROS) production and antioxidant defenses, has emerged as a critical factor influencing oocyte quality and female fertility. This review examines the origins of OS both in vivo and in vitro, highlighting mitochondria and granulosa cells as primary sources, and explores the impact of ovarian aging, obesity, hyperoxic culture conditions, and environmental exposures such as cigarette smoke, endocrine-disrupting chemicals, and controlled ovarian stimulation drugs. This work further explores how OS adversely affects oocyte quality through mechanisms including mitochondrial dysfunction, follicular atresia, meiotic errors, DNA damage, telomere shortening, and reduced fertilization rates. Additionally, this review explores reproductive disorders associated with OS, including polycystic ovary syndrome, endometriosis, premature ovarian insufficiency, and miscarriage. The implications of OS in ART are also addressed, emphasizing the need for strategies to mitigate oxidative damage in both clinical and environmental contexts. This review underscores the significance of OS in female reproductive health, paving the way for potential therapeutic interventions to enhance fertility outcomes.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109011"},"PeriodicalIF":3.3,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703865","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":"Ameliorative effect of curcumin loaded nanoliposomes: A Promising bioactive formulation, against the DBP-induced testicular damage","authors":"Manal R. Bakeer ,&nbsp;Maha M. Rashad ,&nbsp;Fady Sayed Youssef ,&nbsp;Omaima Ahmed ,&nbsp;Seham Samir Soliman ,&nbsp;Ghada E. Ali","doi":"10.1016/j.reprotox.2025.109008","DOIUrl":"10.1016/j.reprotox.2025.109008","url":null,"abstract":"<div><div>Plasticizers are widely employed in various applications. Therefore, these products may have an impact on the biological systems of humans and other organisms. Thus, seeking a potent and eco-friendly protective agent becomes a great challenge. The current study investigated the underlying molecular mechanism associated with the protective effect of curcumin-loaded nanoliposomes (CUR nanoliposomes) against DBP-induced testicular damage. A total of twenty-four adult male rats were split up into four groups: the control group, the CUR nanoliposomes-treated group (100 mg/kg/day by oral gavage), the DBP-treated group (500 mg/kg/day by oral gavage), and the last group that received both treatments simultaneously for 60 days. The results showed that DBP exposure induced Leydig cell damage and testicular injury, represented by decreased serum sex hormone levels, downregulation of <em>INSL3</em> gene expression, elevated testicular LDH, and aberrant sperm rate, as well as pathologically abnormal testicular anatomy. These testicular injuries are associated with redox state imbalance (elevated MDA, reduced CAT activity, and downregulation of <em>Nrf2</em> and <em>SOD</em> gene expression), elevated apoptosis biomarkers (CASP3 and CASP9), and dysregulation of the PI3K/AKT/mTOR pathway. Co-administration of CUR nanoliposomes succeeded in reversing DBP-induced testicular damage. CUR nanoliposome-induced testicular protection could be attributed to the modulation of the PI3K/AKT/mTOR pathway.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109008"},"PeriodicalIF":3.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703800","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":"Effects of cannabidiol, cannabichromene, cannabidivarin, cannabigerol and cannabinol in endometrial cells: Implications for endocrine and senescence modulation","authors":"Patrícia Alves,&nbsp;Cristina Amaral,&nbsp;Bruno M. Fonseca,&nbsp;Luísa G. Sousa,&nbsp;Natércia Teixeira,&nbsp;Georgina Correia-da-Silva","doi":"10.1016/j.reprotox.2025.109006","DOIUrl":"10.1016/j.reprotox.2025.109006","url":null,"abstract":"<div><div>Throughout a woman’s menstrual cycle, endometrial stromal cells (ESCs) undergo cyclic morphological and functional alterations, involving proliferation, differentiation and senescence, modulated in part by steroid hormones and the endocannabinoid system. Disruptions in these processes can lead to endometrial conditions, like endometriosis or miscarriage. In this work, we examined the impact of the phytocannabinoids cannabidiol (CBD), cannabichromene (CBC), cannabidivarin (CBDV), cannabigerol (CBG) and cannabinol (CBN) at 2 µM, by using the St-T1b cell line, a representative model of ESCs. CBDV, CBD and CBN increased <em>ESR1</em> transcription, while it was decreased by CBG. Estrogen receptor α (ER) protein was reduced by CBG and CBN. ER activation, assessed via <em>TFF1</em> expression, was promoted by all cannabinoids except CBN, which suppressed it. Progesterone receptor gene expression increased for CBC, CBDV and CBG treatments, decreasing for CBN. Furthermore, androgen receptor (AR) transcription was upregulated by CBC and CBN, with protein levels increased only by CBN. All the cannabinoids inhibited AR activation. CBN enhanced AKT and ERK1/2 phosphorylation and upregulated <em>AREG</em> expression. Senescence-associated markers <em>YPEL3</em> and <em>LMNB1</em> were modulated by CBC, CBD, and CBN, accompanied by increased β-galactosidase accumulation. Additionally, CBC and CBD upregulated NAPE-PLD mRNA levels, the anandamide synthesis enzyme, although CBC and CBN reduced its protein expression. CBDV increased gene and protein expression of FAAH, the anandamide degrading enzyme. These results suggest that phytocannabinoids may disrupt the interplay between the endometrial endocrine signaling and the endocannabinoid system, as well as modulate senescence in ESCs, potentially affecting female fertility.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109006"},"PeriodicalIF":3.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695178","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}