Reproductive toxicology最新文献

{"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 ,&nbsp;Thalles Fernando Rocha Ruiz ,&nbsp;Gervásio Evangelista Brito Filho ,&nbsp;Luara Jesus Ferrato ,&nbsp;Simone Jacovaci Colleta ,&nbsp;Ellen Cristina Rivas Leonel ,&nbsp;Sebastião Roberto Taboga","doi":"10.1016/j.reprotox.2025.109013","DOIUrl":"10.1016/j.reprotox.2025.109013","url":null,"abstract":"<div><div>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 50 μg/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.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 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}

{"title":"Lipopolysaccharide-induced inflammation modulates testicular kisspeptin system in mice","authors":"Jaldhi ,&nbsp;Shweta ,&nbsp;Shashank Kumar Maurya ,&nbsp;Amrita Bakshi","doi":"10.1016/j.reprotox.2025.109005","DOIUrl":"10.1016/j.reprotox.2025.109005","url":null,"abstract":"<div><div>Kisspeptin, a neuropeptide hormone, plays an indispensable role in regulating reproduction. Acting upstream of gonadotropin-releasing hormone, it controls gonadotropin release, and concomitant gonadal functions, and in turn, is regulated by gonadal steroid hormones. Nevertheless, expression of kisspeptin (Kiss1) and its receptor (Kiss1r) is reported in tissues other than hypothalamus, including testes. Since immune-challenged conditions lead to compromised reproductive functions, the present work emphasizes on investigating regulation of the testicular kisspeptin system in adult mice by lipopolysaccharide (LPS)-induced inflammation. <em>In vivo</em> chronic treatment of LPS for 7 days caused irregularly-shaped seminiferous tubules with reduced perimeter, diameter and cross-sectional area, distorted arrangement of spermatogenic cells, disrupted connective tissue leading to increased interstitial space and reduced sperm count. Further, elevated expression level of pro-inflammatory cytokine, <em>Tnfα,</em> in the testis validated the induction of inflammation. Regarding the kisspeptin system, a significant increase in testicular Kiss1 but a decrease in Kiss1r expression was observed at both gene and protein levels, implying a possible compensatory role of testicular kisspeptin to control reproductive functions under an infectious state. Further, an <em>in vitro</em> treatment of testicular fragments with LPS was conducted for 3 h and 6 h to understand the direct effect of inflammation on the testicular kisspeptin system. An increased <em>Tnfα</em> but decreased <em>Tgfβ1</em> expression was observed at both time points. At the transcript level, <em>Kiss1</em> showed a reduced expression at 6 h but no change at 3 h of LPS treatment. Regarding <em>Kiss1r</em>, an increased expression at 3 h but decreased at 6 h was seen. At the protein level, decreased levels of testicular Kiss1 was observed at both the time points while Kiss1r exhibited no significant change. Hence, the present work demonstrated modulation of the testicular kisspeptin system by LPS-induced inflammation.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109005"},"PeriodicalIF":3.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703908","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":"Maternal application of tropical antifungal medication is associated with reduced steroid hormone levels during minipuberty and shorter anogenital distance in offspring from 3 months to 9 years of age: Odense Child Cohort","authors":"Sarah Munk Andreasen ,&nbsp;Anna-Patricia Iversen ,&nbsp;Lars Christian Lund ,&nbsp;Margit Bistrup Fischer ,&nbsp;Anna-Maria Andersson ,&nbsp;Naja Kamuk Rauer ,&nbsp;Gylli Mola ,&nbsp;Anders Juul ,&nbsp;Casper P. Hagen ,&nbsp;Tina Kold Jensen","doi":"10.1016/j.reprotox.2025.109007","DOIUrl":"10.1016/j.reprotox.2025.109007","url":null,"abstract":"<div><div>Vaginal candidiasis affects about 20 % of pregnant women and is usually treated with over-the-counter topical antifungal medication (azoles). Vaginal or transdermal application of azoles are absorbed and detectable in circulation. Azoles inhibit CYP51, which is crucial for the integrity of fungal cellular membranes. However, cell cultures have shown that azoles also affect steroidogenesis. This study investigated maternal antifungal application during pregnancy and the association with reproductive hormones during <em>minipuberty</em> and anogenital distance (AGD) the in the offspring from infancy to 9 years of age. In the Odense Child Cohort (2010–2012), women completed questionnaires about antifungal application during pregnancy. Serum concentrations of luteinising hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estrone (E1), estradiol (E2), Δ4-androstenedione (adione), 17α-hydroxyprogesterone (17-OHP) and dehydroepiandrosterone-sulphate (DHEAS) were analysed in 454 infants at 3 months. AGD was assessed at 3, 18 months and 3, 5, 7 and 9 years of age, with 1792 measurements. Topical antifungal application during pregnancy was reported by 35 women. In boys, maternal application before GW 19 was associated with shorter AGD as well as lower adrenal hormone levels. In girls, application before GW 19 was associated with longer AGD and lower reproductive and adrenal hormone levels, while application after GW 19 was associated with shorter AGD, while hormone levels did not differ. Given the small number of cases, the findings should be interpreted with caution. The widespread use of over-the-counter antifungals appears to affect AGD and hormone production in offspring, which is concerning and may have long-term consequences for reproductive health.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109007"},"PeriodicalIF":3.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695177","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":"Maternal smoking affects human fetal X-inactivation","authors":"Sanam Zeib Khan ,&nbsp;Linn Salto Mamsen ,&nbsp;Erik Ernst ,&nbsp;Esben Budtz-Jørgensen ,&nbsp;Claus Yding Andersen ,&nbsp;Niels Tommerup","doi":"10.1016/j.reprotox.2025.109010","DOIUrl":"10.1016/j.reprotox.2025.109010","url":null,"abstract":"<div><div>Females inactivate one of their two X-chromosomes in each cell before implantation, at a time where any factor that affect the number of these primordial cells may lead to deviation from the usual random choice. Thus, non-random (skewed) X-inactivation may occur due to early stochastic effects in the limited primordial pool size. The primodial pool size can be calculated from the variance of the ratio between the unmethylated and methylated CAG-repeats within exon 1 of the androgen receptor gene (<em>AR</em>) corresponding to the active and inactive X-chromosome (X-inactivation (XI)-ratio), respectively. Since maternal smoking during pregnancy is associated with a general growth inhibition and a reduced number of fetal gonadal cells, we have tested the XI-ratios in tissues obtained from fetuses of smoking (n = 8) and non-smoking (n = 10) mothers in connection with legal termination of the pregnancy. A tighter distribution of XI-ratios was seen in tissues from fetuses in the smoking group. Combined with more skewed X-inactivation (&gt;=80 %) and a higher mean XI-ratio in the fetal samples from pregnancies of non-smoking mothers, this support a larger pool of primordial cells in fetuses exposed to smoking, suggesting that smoking during pregnancy delays fetal X inactivation.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109010"},"PeriodicalIF":2.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708590","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}