{"title":"3-chloro-1,2-propanediol induces oxidative stress and promotes testicular damage and infertility in rats through CYP2C9","authors":"","doi":"10.1016/j.reprotox.2024.108633","DOIUrl":"10.1016/j.reprotox.2024.108633","url":null,"abstract":"<div><p>3-chloro-1,2-propanediol (3-MCPD) is a newly discovered food process pollutant with nephrotoxicity. And the mechanism by which 3-MCPD affects male spermatogenesis has not been fully studied. Cell viability, blood-testis barrier (BTB) related protein, progesterone content, reactive oxygen species (ROS) generation, and cell apoptosis were determined by a CCK8 assay, western blot, ELISA, flow cytometry, and TUNEL staining, respectively. Wistar rats were divided into three groups: low-dose 3-MCPD, high-dose 3-MCPD, and control. Sperm parameters, hormonal levels, and biomarkers of oxidative stress in the testis and epididymis were detected by ELISA. Multiple molecular experiments including molecular docking and western blot were used to elucidate the underlying mechanisms. 3-MCPD affects testicular cell activity, and promotes ROS production and apoptosis. Disrupting the integrity of BTB in the body, downregulating sex hormones and sperm quality, and promoting apoptosis. 3-MCPD may function through CYP2C9. This study preliminarily explores the mechanism by which 3-MCPD affects spermatogenesis. It was found that 3-MCPD destroys the structure and function of BTB and damages the testicular function of male mice, thus affecting the process of spermatogenesis via CYP2C9.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S089062382400100X/pdfft?md5=5b0a78b252346f78cff851e6fed39039&pid=1-s2.0-S089062382400100X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470500","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}
Natalia P. Silva , Charles S. da Costa , Kayke L. Barbosa , Cidália de F. Januario , Leticia N. Gama-de-Souza , Cinthia Breves , Rodrigo S. Fortunato , Leandro Miranda-Alves , Miriane de Oliveira , Celia R. Nogueira , Jones B. Graceli
{"title":"Subacute tributyltin exposure alters the development and morphology of mammary glands in association with CYP19A1 expression in female rats","authors":"Natalia P. Silva , Charles S. da Costa , Kayke L. Barbosa , Cidália de F. Januario , Leticia N. Gama-de-Souza , Cinthia Breves , Rodrigo S. Fortunato , Leandro Miranda-Alves , Miriane de Oliveira , Celia R. Nogueira , Jones B. Graceli","doi":"10.1016/j.reprotox.2024.108635","DOIUrl":"10.1016/j.reprotox.2024.108635","url":null,"abstract":"<div><p>Tributyltin (TBT) is an endocrine-disrupting chemical (EDC) related to reproductive dysfunctions. However, few studies have investigated the effects of TBT exposure on mammary gland development. Thus, we assessed whether subacute TBT exposure causes irregularities in mammary gland development. We administered TBT (100 and 1,000 ng/kg/day for 30 days) to female rats from postnatal day (PND) 25 to PND 55, and mammary gland development, morphology, inflammation, collagen deposition, and protein expression were evaluated. Abnormal mammary gland development was observed in both TBT groups. Specifically, TBT exposure reduced the number of terminal end buds (TEBs), type 1 (AB1) alveolar buds, and type 2 (AB2) alveolar buds. An increase in the lobule and differentiation (DF) 2 score was found in the mammary glands of TBT rats. TBT exposure increased mammary gland blood vessels, mast cell numbers, and collagen deposition. Additionally, both TBT rats exhibited intraductal hyperplasia and TEB-like structures. An increase in estrogen receptor alpha (ERα), progesterone receptor (PR), and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) - positive cells was observed in the mammary glands of TBT rats. A strong negative correlation was observed between CYP19A1- positive cells and TEB number. In addition, CYP19A1 - positive cells were positively correlated with mammary gland TEB-like structure, ductal hyperplasia, inflammation, and collagen deposition. Thus, these data suggest that TBT exposure impairs mammary gland development through the modulation of CYP19A1 signaling pathways in female rats.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470503","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}
Linda Schenk , Meng-Rung Ho , Piia Taxell , Pasi Huuskonen , Mimmi Leite , Inese Martinsone , Karl-Christian Nordby , Linda Paegle , Loreta Strumylaite
{"title":"Occupational exposure limits for reproductive toxicants – A comparative analysis","authors":"Linda Schenk , Meng-Rung Ho , Piia Taxell , Pasi Huuskonen , Mimmi Leite , Inese Martinsone , Karl-Christian Nordby , Linda Paegle , Loreta Strumylaite","doi":"10.1016/j.reprotox.2024.108649","DOIUrl":"10.1016/j.reprotox.2024.108649","url":null,"abstract":"<div><p>We investigated the level of protection of reproductive and developmental toxicity offered through occupational exposure limits (OELs) and Derived No-Effect Levels for workers’ inhalation exposure (wDNELs). We compared coverage of substances that have a harmonised classification as reproductive toxicant 1 A or 1B (Repr.1 A/B), numerical values and scientific basis of 12 lists of OELs and wDNELs from REACH Registrants’ and the Committee for Risk Assessment. Across the 14 sources of OELs and wDNELs, 53 % of the Repr1A/B-substances had at least one exposure limit (counting groups of metals as one entry). Registrants’ wDNELs covered the largest share, 40 %. The numerical values could be highly variable for the same substance across the lists. How often reproductive toxicity is identified as the critical effect varies between the examined lists, both due to different assessments of the same substance and different substance coverage. Reviewing the margin of safety to reproductive toxicity cited in the documents, we found that 15 % of safety margins were lower to reproductive toxicity than the critical effect. To conclude, neither the REACH nor work environment legislation supply wDNELs or OELs for a substantial share of known reproductive toxicants. EU OELs cover among the fewest substances in the range, and in many cases national OELs or wDNELs are set at more conservative levels.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890623824001163/pdfft?md5=b53065ede8a7e776d840d6db6f733e9a&pid=1-s2.0-S0890623824001163-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470502","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}
Ola S. Davis , Olivia L.M. Scandlan , Reem Sabry , Mahta Ghaffarzadeh , Thomas G. Hannam , Alexander Lagunov , Laura A. Favetta
{"title":"High seminal BPA in IVF patients correlates with lower sperm count and up-regulated miR-21 and miR-130a","authors":"Ola S. Davis , Olivia L.M. Scandlan , Reem Sabry , Mahta Ghaffarzadeh , Thomas G. Hannam , Alexander Lagunov , Laura A. Favetta","doi":"10.1016/j.reprotox.2024.108651","DOIUrl":"10.1016/j.reprotox.2024.108651","url":null,"abstract":"<div><p>Bisphenol A (BPA) is a widespread industrial chemical, used as the key monomer of polycarbonate plastics and epoxy resins. BPA has been detected in human seminal fluid and has been correlated with changes in sperm parameters, crucial in determining male fertility. In this study, semen samples were collected from 100 patients aged 29–47 years undergoing fertility assessment between 2021 and 2023 and analyzed according to WHO guidelines. BPA levels in the seminal plasma were then measured through an enzyme-linked immunosorbent assay (ELISA) and compared to sperm quality metrics. The relative mRNA/miRNA expression of key genes associated to male reproduction, including androgen receptor, miR-34c, miR-21, miR-130a, was then quantified and compared between groups with high or low BPA content. Our results revealed that BPA levels were increased with age and were negatively correlated with sperm counts (p<0.05). The negative correlation remained significant when patients were age-matched. No other relationships between seminal BPA and motility, morphology or DNA fragmentation levels were observed. qPCR analysis showed that androgen receptor mRNA expression was significantly greater in sperm with high seminal BPA (p<0.05). Moreover, we found that the expression of miR-21 and miR-130a was also upregulated in the higher BPA group (p<0.05). These results display a relationship between BPA content in the semen and male fertility parameters, and provide insights into the molecular mechanisms through which BPA may be affecting male reproductive capability. Ultimately, this research can potentially drive changes to guidelines and exposure limits for BPA exposure.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890623824001187/pdfft?md5=9e4f3649d06ff3121d80363073d98028&pid=1-s2.0-S0890623824001187-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141459015","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}
John L.P. Coimbra , Gabriel Campolina-Silva , Daniel F. Lair , Luiz O. Guimarães-Ervilha , Ana C.F. Souza , Cleida A. Oliveira , Guilherme M.J. Costa , Mariana Machado-Neves
{"title":"Subchronic intake of arsenic at environmentally relevant concentrations causes histological lesions and oxidative stress in the prostate of adult Wistar rats","authors":"John L.P. Coimbra , Gabriel Campolina-Silva , Daniel F. Lair , Luiz O. Guimarães-Ervilha , Ana C.F. Souza , Cleida A. Oliveira , Guilherme M.J. Costa , Mariana Machado-Neves","doi":"10.1016/j.reprotox.2024.108647","DOIUrl":"10.1016/j.reprotox.2024.108647","url":null,"abstract":"<div><p>The prostate gland is one of the main sites of hyperplasia and cancer in elderly men. Numerous factors have been demonstrated to disrupt prostate homeostasis, including exposure to environmental pollutants. Arsenic is a metalloid found ubiquitously in soil, air, and water, which favors human poisoning through the involuntary intake of contaminated drinking water and food and has harmful effects by increasing the oxidative stress response. This study aimed to investigate the effects of prolonged exposure to arsenic at environmentally relevant concentrations on the prostate biology of adult Wistar rats. Thirty 80-day-old male rats were divided into three experimental groups. Rats from the control group received filtered water, whereas animals from the arsenic groups ingested 1 mg L<sup>−1</sup> and 10 mg L<sup>−1</sup> of arsenic, in the form of sodium arsenite, daily. The arsenic solutions were provided <em>ad libitum</em> in the drinking water for eight weeks. Our results showed that 1 mg L<sup>−1</sup> and 10 mg L<sup>−1</sup> of arsenic made the prostate susceptible to evolving benign and premalignant histopathological changes. While the ingestion of 1 mg L<sup>−1</sup> of arsenic reduced SOD activity only, 10 mg L<sup>−1</sup> diminished SOD and CAT activity in the prostate tissue, culminating in high MDA production. These doses, however, did not affect the intraprostatic levels of DHT and estradiol. In conclusion, exposure to arsenic at environmentally relevant concentrations through drinking water induces histological and oxidative stress-related changes in the prostate of adult rats, strengthening the between arsenic exposure and prostate disorders.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443219","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}
Yuanyuan Zhou , Fenglei Ye , Linyun Zhang , Quanmin Kang , Yujia Luo , Nan Jiang , Lijun Lou , Yuchan Mao , Liya Wang , Fan Jin
{"title":"The role of DNA damage response in human embryonic stem cells exposed to atmospheric oxygen tension: Implications for embryo development and differentiation","authors":"Yuanyuan Zhou , Fenglei Ye , Linyun Zhang , Quanmin Kang , Yujia Luo , Nan Jiang , Lijun Lou , Yuchan Mao , Liya Wang , Fan Jin","doi":"10.1016/j.reprotox.2024.108648","DOIUrl":"10.1016/j.reprotox.2024.108648","url":null,"abstract":"<div><p>Previous retrospective cohort studies have found that, compared with oxygen tension in the uterus and fallopian tubes (2 %-8 %), exposure of pre-implantation embryos to atmospheric oxygen tension (AtmO<sub>2</sub>, 20 %) during assisted reproductive technology(ART) can affect embryo quality, pregnancy outcomes and offspring health. However, current research on the effects and mechanisms of AtmO<sub>2</sub> on the development of embryos and offspring is mainly limited to animal experiments. Human embryonic stem cells (hESCs) play a special and irreplaceable role in the study of early human embryonic development. In this study, we used hESCs as a model to elucidate the possible effects and mechanisms of AtmO<sub>2</sub> exposure on human embryonic development. We found that exposure to AtmO<sub>2</sub> can reduce cell viability, produce oxidative stress, increase DNA damage, initiate DNA repair, activate autophagy, and increase cell apoptosis. We also noticed that approximately 50 % of hESCs survived, adapted and proliferated through high expression of self-renewal and pluripotency regulatory factors, and affected embryoid body differentiation. These data indicate that hESCs experience oxidative stress, accumulation of DNA damage, and activate DNA damage response under the selective pressure of AtmO<sub>2</sub>.Some hESCs undergo cell death, whereas other hESCs adapt and proliferate through increased expression of self-renewal genes. The current findings provide in vitro evidence that exposure to AtmO<sub>2</sub> during the early preimplantation stage negatively affects hESCs.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890623824001151/pdfft?md5=d36a8d08e2023ee9015c0c027b8e3b81&pid=1-s2.0-S0890623824001151-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443220","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}
Ravinder Kumar , Ashwini Oke , Beth Rockmill , Matthew de Cruz , Rafael Verduzco , Anura Shodhan , Xavier Woodruff-Madeira , Dimitri P. Abrahamsson , Julia Varshavsky , Juleen Lam , Joshua F. Robinson , Patrick Allard , Tracey J. Woodruff , Jennifer C. Fung
{"title":"Rapid identification of reproductive toxicants among environmental chemicals using an in vivo evaluation of gametogenesis in budding yeast Saccharomyces cerevisiae","authors":"Ravinder Kumar , Ashwini Oke , Beth Rockmill , Matthew de Cruz , Rafael Verduzco , Anura Shodhan , Xavier Woodruff-Madeira , Dimitri P. Abrahamsson , Julia Varshavsky , Juleen Lam , Joshua F. Robinson , Patrick Allard , Tracey J. Woodruff , Jennifer C. Fung","doi":"10.1016/j.reprotox.2024.108630","DOIUrl":"10.1016/j.reprotox.2024.108630","url":null,"abstract":"<div><p>Infertility affects ∼12 % of couples, with environmental chemical exposure as a potential contributor. Of the chemicals that are actively manufactured, very few are assessed for reproductive health effects. Rodents are commonly used to evaluate reproductive effects, which is both costly and time consuming. Thus, there is a pressing need for rapid methods to test a broader range of chemicals. Here, we developed a strategy to evaluate large numbers of chemicals for reproductive toxicity via a yeast, <em>S. cerevisiae</em> high-throughput assay to assess gametogenesis as a potential new approach method (NAM). By simultaneously assessing chemicals for growth effects, we can distinguish if a chemical affects gametogenesis only, proliferative growth only or both. We identified a well-known mammalian reproductive toxicant, bisphenol A (BPA) and ranked 19 BPA analogs for reproductive harm. By testing mixtures of BPA and its analogs, we found that BPE and 17 β-estradiol each together with BPA showed synergistic effects that worsened reproductive outcome. We examined an additional 179 environmental chemicals including phthalates, pesticides, quaternary ammonium compounds and per- and polyfluoroalkyl substances and found 57 with reproductive effects. Many of the chemicals were found to be strong reproductive toxicants that have yet to be tested in mammals. Chemicals having affect before meiosis I division vs. meiosis II division were identified for 16 gametogenesis-specific chemicals. Finally, we demonstrate that in general yeast reproductive toxicity correlates well with published reproductive toxicity in mammals illustrating the promise of this NAM to quickly assess chemicals to prioritize the evaluation for human reproductive harm.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890623824000972/pdfft?md5=00345fb20b929dab52ca32fa8795fd8d&pid=1-s2.0-S0890623824000972-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437434","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}
Tat-Chuan Cham , Fahar Ibtisham , Ahmad Al-Dissi , Ali Honaramooz
{"title":"An in vitro testicular organoid model for the study of testis morphogenesis, somatic cell maturation, endocrine function, and toxicological assessment of endocrine disruptors","authors":"Tat-Chuan Cham , Fahar Ibtisham , Ahmad Al-Dissi , Ali Honaramooz","doi":"10.1016/j.reprotox.2024.108645","DOIUrl":"https://doi.org/10.1016/j.reprotox.2024.108645","url":null,"abstract":"<div><p>Male reproductive capacity has fallen considerably in recent decades; in addition, the incidence of testicular cancer has increased in many developed countries. The cause of this phenomenon is unknown, but environmental toxicants are considered a major contributing factor. To study potential reproductive toxicants, robust <em>in vitro</em> testis models are needed. We have recently established a porcine testis organoid system with a high resemblance to the architectures of innate testis tissue. Here, we further investigated the testis morphogenesis, cell maturation, and endocrine function of the testis organoids. We also challenged this system with abiraterone, a steroidogenic inhibitor, to validate its suitability as an <em>in vitro</em> platform for endocrine toxicology tests. Our results showed that the testis cells in the organoids reorganize into testis cordal structures, and the cordal relative areas increase in the organoids over time of culture. Moreover, the diameters and cell numbers per cross-section of the cordal structures increased over time. Interestingly, Sertoli cells in the organoids gradually underwent maturational changes by showing increased expression of androgen receptors, decreased expression of the anti-müllerian hormone, and formation of the blood-testis barrier. Next, we confirmed that the organoids respond to hormonal stimulation and release multiple sex hormones, including testosterone, estradiol, and progesterone. Finally, we showed that the production of testosterone and estradiol in this system can be inhibited in response to the steroidogenic inhibitor. Taken together, our organoid system provides a promising <em>in vitro</em> platform for male reproductive toxicology studies on testis morphogenesis, somatic cell maturation, and endocrine production.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890623824001126/pdfft?md5=d9c0b85b338e25d22d8f54f36844534c&pid=1-s2.0-S0890623824001126-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141422968","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}
Luyao Yang , Shuangshuang Wang , Jing Jin , Jiahui Wang , Wenyue Chen , Yun Xue , Liang Sheng , Yongning Zhai , Weifeng Yao
{"title":"Sucralose triggers insulin resistance leading to follicular dysplasia in mice","authors":"Luyao Yang , Shuangshuang Wang , Jing Jin , Jiahui Wang , Wenyue Chen , Yun Xue , Liang Sheng , Yongning Zhai , Weifeng Yao","doi":"10.1016/j.reprotox.2024.108644","DOIUrl":"10.1016/j.reprotox.2024.108644","url":null,"abstract":"<div><p>Sucralose, the extensively utilized sweetener, might lead to metabolic disorders with prolonged consumption, but it remains uncertain if sucralose has any impact on female reproductive health. We incorporated sucralose into drinking water and observed food intake, body weight, estrous cycle, follicular development, serum hormones, and insulin sensitivity of mice. The mice did not experience any changes in their food intake or body weight after consuming sucralose. However, they displayed irregularities in the estrous cycle, marked by a reduced count of primordial, primary, and secondary follicles, coupled with a significant increase in the number of antral follicles. There was a decline in follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P4) levels, while testosterone (T) and luteinizing hormone (LH) levels surged, leading to a notable elevation in the LH / FSH ratio. Sucralose also induced insulin resistance, as evidenced by elevated insulin levels and impaired insulin tolerance, which responded to an increase in bacterial-derived serum endotoxin. By eliminating insulin resistance with rosiglitazone (RSG), eradicating intestinal flora-derived endotoxins with neomycin (NEO), or enhancing intestinal barrier function with indole-3-carbinol (I3C), the abnormalities in estrous cycle, disruptions in follicular development, hormonal imbalances and elevation in serum endotoxins induced by sucralose were successfully reversed. The present study indicates that sucralose-induced follicular dysplasia in mice is probably related to impaired intestinal permeability, infiltration of endotoxins, initiation of systemic inflammation, and insulin resistance.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331646","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}
Jiawei Sun , Huan Chen , Xu Xu , Yaping Dou , Baofa Wu , Hongyang Zhang , Song Shang , Wuzhuang Sun
{"title":"Effect of maternal cigarette smoke exposure on COPD progression in offspring mice","authors":"Jiawei Sun , Huan Chen , Xu Xu , Yaping Dou , Baofa Wu , Hongyang Zhang , Song Shang , Wuzhuang Sun","doi":"10.1016/j.reprotox.2024.108646","DOIUrl":"10.1016/j.reprotox.2024.108646","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the impact of maternal smoking on chronic obstructive pulmonary disease (COPD) progression in offspring.</p></div><div><h3>Methods</h3><p>Using female C57BL/6 J mice, a maternal cigarette smoke exposure (CSE) model was established. Mice were exposed to cigarette smoke for 2 hours/day, 7 days/week, with a minimum 4-hour interval between exposures. Experimental groups included control (Con), pregnancy exposure (AS), pre-pregnancy exposure (SA), and pre-pregnancy + pregnancy exposure (SS). Lung function tests (Penh, PAU, TVb, EF50, Tr) were conducted on male offspring at 7 weeks. Histopathology, electron microscopy, and protein level changes were examined.</p></div><div><h3>Results</h3><p>Lung function tests revealed significant impairments in Penh, PAU, TVb, EF50, and Tr in offspring across all exposure scenarios. Specifically, AS experienced significant lung function impairment and mitochondrial dysfunction in offspring, with noticeable pulmonary lesions and increased apoptosis. SA showed similar or even more severe lung function impairment and cellular apoptosis. SS exhibited the most pronounced effects, with the highest levels of lung dysfunction, mitochondrial damage, and apoptosis. Histopathological analysis showed pulmonary lesions in offspring exposed to maternal CSE. Flow cytometry revealed increased apoptosis and reduced mitochondrial membrane potential in offspring lung cells. Electron microscopy confirmed mitochondrial dysfunction. Upregulation of apoptotic proteins and downregulation of anti-apoptotic protein Bcl-2 were found in offspring lung tissue exposed to maternal CSE.</p></div><div><h3>Conclusion</h3><p>Maternal smoking induces impaired lung function, pulmonary lesions, and mitochondrial dysfunction in offspring, regardless of exposure timing and duration. Additionally, it alters expression of apoptosis-related proteins in offspring lung tissue, potentially contributing to COPD susceptibility.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331645","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}