{"title":"Measurement of Androgen-Sensitive Preweaning Developmental Landmarks in Rodents: Best Practices and Toxicological Significance","authors":"Ross Gillette, Justin D. Vidal, Pragati S. Coder","doi":"10.1002/bdr2.2482","DOIUrl":"https://doi.org/10.1002/bdr2.2482","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Anogenital distance and nipple/areola(e) retention are biomarkers for monitoring normal age-appropriate masculinization of male offspring required by U.S. EPA and OECD guidelines for chemicals. OECD Guidance Document 150 considers both landmarks as sensitive, apical endpoints. For the last century, it has been known that nipple regression in male rodents is complete by late gestation and there are no external or microscopic traces of a nipple at the time of birth. Adverse effects of antiandrogen exposures in humans are well documented, and AGD/NR serve as surrogates for effects on physical and sexual development, although the human relevance of these individual endpoints and endocrine disruption in rodents continues to be debated. The European Chemicals Agency (ECHA) published its reports on the EOGRTS Review Project and ranked 37% AGD and 83% NR datasets across 72 studies as limited or of unacceptable quality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed AGD/NR data from 142 rodent studies based on sound scientific principles and per the agency's scoring criteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and Conclusion</h3>\u0000 \u0000 <p>For AGD, our data met standards for precision, variability, and separation of sexes. For NR, our data demonstrated that spontaneous nipple/areolae retention is far less common than asserted by the agency. We propose that the 5-point rating scale used by ECHA to rate NR data has considerable limitations as it is based on data from a single publication that evaluated a limited number of litters/studies. Based on our review of the literature, ECHA recommendations, and the data presented herein, we put forth best practice recommendations for data collection, analysis, and reporting in an effort to improve future data quality, interpretation, and coherence for regulatory review.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 5","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926168","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}
Zheng Guo, Xinxin Lv, Jianwen Li, Shiping Yue, Jing Du
{"title":"Blastocyst Cavity Expansion Promotes Cell Polarization During Early Development of Mouse Embryos","authors":"Zheng Guo, Xinxin Lv, Jianwen Li, Shiping Yue, Jing Du","doi":"10.1002/bdr2.2484","DOIUrl":"https://doi.org/10.1002/bdr2.2484","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cell polarization is an important morphological process that is crucial for the formation and function of tissues and organs. The blastocyst cavity expansion is an apparent event during the second cell fate specification in mouse embryos, yet its impact on cell polarization remains unclear. In this study, we investigate the effects of blastocyst cavity expansion on cell polarization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The methods of this study involve hyperosmotic treatment or disruption of TE cortical tension by laser ablation, combined with immunofluorescence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that inhibition of the blastocyst cavity expansion through hypertonic treatment or disruption of TE cortical tension by laser ablation suppresses the levels of the ζ isotype of protein kinase C (PKC ζ) which is a member of the atypical PKC subfamily involved in cell polarization. We further found that during the embryonic stages E3.5 to E4.0, the expression of extracellular signal-regulated kinase 1 (ERK1), a key upstream regulator of PKC ζ, is altered in a similar tendency to that of PKC ζ, indicating a potential regulatory function of ERK1 in cell polarization during early development of mouse embryos.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study reveals the function of the mechanical behavior of embryos in cell polarization of early mammalian embryos. The relationship between cell polarization and blastocyst cavity expansion in early embryonic development provides a new understanding, thereby offering fresh insights for the screening and detection of indicators for normal blastocyst development.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 5","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926108","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":"Embryo-Fetal Developmental Toxicity and Toxicokinetics Studies of YWS1903, a Novel Potassium-Competitive Acid Blocker, in Pregnant Rats","authors":"Chaoying Lu, Hongqun Qiao","doi":"10.1002/bdr2.2481","DOIUrl":"https://doi.org/10.1002/bdr2.2481","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In this study, we investigated the developmental and reproductive toxicity of YWS1903, a novel potassium-competitive acid blocker, in pregnant Sprague–Dawley rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>YWS1903 was administered orally at doses of 0 (control), 20, 60, and 200 mg kg<sup>−1</sup> from gestation days 6 to 17 (<i>n</i> = 24 per group). Concurrent toxicokinetic analysis was conducted to characterize the toxicokinetic profile and placental transfer of YWS1903.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Aside from hair loss at the highest dose, no significant maternal toxicity was observed up to 200 mg kg<sup>−1</sup>. Fetal assessments revealed reductions in body weight and crown-rump length at 200 mg kg<sup>−1</sup>, alongside increased skeletal malformations, but no visceral abnormalities were detected. Toxicokinetic linearity studies revealed that within the 20–200 mg kg<sup>−1</sup> dose range, both <i>C</i><sub>max</sub> and AUC<sub>0-t</sub> of YWS1903 exhibited disproportionate increases following initial and final administrations. In the high-dose group, the escalation in AUC<sub>0-t</sub> substantially exceeded the corresponding dose changes, suggesting potential saturation of metabolic pathways at higher exposure levels. YWS1903 was shown to cross the placenta, although fetal plasma concentrations were consistently lower than maternal levels, suggesting reduced direct fetal exposure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The no observed adverse effect level was established at 60 mg kg<sup>−1</sup>, supporting the compound's safety at moderate doses. These findings provide valuable insights into YWS1903's developmental and reproductive safety profile and offer reference for its clinical application as a therapeutic agent for gastroesophageal reflux disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 5","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914128","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}
L. David Wise, Alan M. Hoberman, Christopher J. Bowman, Elise M. Lewis
{"title":"Perspectives on Implementing Virtual Control Groups in Developmental and Reproductive Toxicity Studies","authors":"L. David Wise, Alan M. Hoberman, Christopher J. Bowman, Elise M. Lewis","doi":"10.1002/bdr2.2479","DOIUrl":"https://doi.org/10.1002/bdr2.2479","url":null,"abstract":"<div>\u0000 \u0000 <p>The use of virtual control groups (VCGs) in nonclinical toxicology studies was first proposed in 2020 with the main purpose of reducing animal use while integrating historical control data (HCD) to enhance study interpretation. The use of VCGs has gained increasing attention as evidenced by an increasing number of publications that highlight implementation challenges. Laboratories that conduct harmonized studies with standardized procedures, consistent environmental conditions, and validated electronic databases are well-suited to implement VCGs in future nonclinical safety studies. We suggest that individual laboratories conducting rodent and rabbit developmental and reproductive toxicity studies should begin planning for VCG implementation. If possible, a harmonized approach to VCG implementation by multiple laboratories will lend credence to regulatory approval. We apply the six-step VCG implementation framework from Palazzi et al. to the routine GLP studies covered by international guidelines, which emphasize validation through retrospective and prospective trials. We discuss the risks and challenges to VCG implementation that have been previously presented. To address some of these concerns, a hybrid approach is proposed that combines a small concurrent control group (CCG) with multiple virtual control (VC) animals from the same test facility. The inclusion of a CCG addresses the need to monitor for disease and environmental changes and prevent depletion of HCD. Two approaches to the selection of VC animals are discussed. Given that developmental and reproductive toxicity studies use the most animals in nonclinical safety studies, we support the timely implementation of VCGs to significantly reduce these animal numbers.</p>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 5","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905115","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":"Racial and Ethnic Disparities in California's Use of Agricultural Pesticides","authors":"Caroline Cox, Jonathan K London","doi":"10.1002/bdr2.2480","DOIUrl":"https://doi.org/10.1002/bdr2.2480","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The objective of this study is to determine whether the current use of agricultural pesticides in California is unequally distributed with respect to race and ethnicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted the analysis using publicly available data from the California Department of Pesticide Regulation and the US Census Bureau. We used two relatively simple statistical techniques to conduct the analysis: concentration curves and linear regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We showed that agricultural pesticide use in California is not distributed equally with respect to racial and ethnic composition. Similar patterns held whether we looked at current data, data from past years, or individual pesticides of public health concern. Importantly for public health, the use of a group of pesticides that, according to California regulations, causes reproductive harm also was concentrated in areas with a lower percentage of non-Hispanic Whites. The percentage of the population that is Hispanic/Latinx is a strong statistical driver of these inequalities. The data also show similar patterns of inequity in pesticide use with respect to three socioeconomic factors: income, education level, and prevalence of agricultural employment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Policy and regulatory actions are needed to reduce these disparities and maintain California's leadership in environmental justice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 5","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909249","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}
Shimaa Antar Fareed, Heba El-Sayed Mostafa, Yousif Mohamed Saleh, Yasmin Islam Magdi, Islam Mohamed Magdi Ammar
{"title":"How Does Maternal Lipopolysaccharide Exposure Impact Prenatal Testicular Development in Rats, and Could α-Tocopherol Provide a Protective Effect? A Histological, Immunohistochemical and Biochemical Study","authors":"Shimaa Antar Fareed, Heba El-Sayed Mostafa, Yousif Mohamed Saleh, Yasmin Islam Magdi, Islam Mohamed Magdi Ammar","doi":"10.1002/bdr2.2469","DOIUrl":"https://doi.org/10.1002/bdr2.2469","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lipopolysaccharides or endotoxins trigger proinflammatory cytokines and nitric oxide release, whereas α-tocopherol protects cells from oxidative damage. This study investigated the effects of maternal lipopolysaccharide exposure on prenatal testicular development in male rat offspring and assessed α-tocopherol's protective role.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Forty pregnant female rats were divided into four groups. Group I (control) included a negative control receiving normal saline and a positive control receiving 30 mg/kg of α-tocopherol intraperitoneally from the 3rd to 18th gestational day. Group II received 50 mg/kg of lipopolysaccharides intraperitoneally from the 13th to 17th gestational day, whereas Group III received both α-tocopherol and lipopolysaccharides at the same dosages. On the seventh day postpartum, fetuses were weighed, sexed, and dissected; sera from male fetuses were collected for biochemical analysis, and fetal testes were used for histology, immunohistochemistry, and morphometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Rats treated with lipopolysaccharide showed reduced body weight, testosterone, and luteinizing hormone levels, with histopathological changes, including thickened testicular capsules and abnormalities in the number, size, shape, and cellular components of seminiferous tubules. These adverse effects were improved by α-tocopherol supplementation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We concluded that lipopolysaccharide exposure during pregnancy impairs testicular development and steroidogenesis, which are ameliorated by α-tocopherol coadministration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 5","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143896961","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":"Correction to “Cognitive, Behavioral and Educational Outcomes in Children Aged 5–11 Years With Spina Bifida in Northern Ireland”","authors":"","doi":"10.1002/bdr2.2478","DOIUrl":"https://doi.org/10.1002/bdr2.2478","url":null,"abstract":"<p>Parajuli, Y. G. and Sinclair, M. 2025. “Cognitive, Behavioral and Educational Outcomes in Children Aged 5–11 Years With Spina Bifida in Northern Ireland.” <i>Birth Defects Research</i> 117: e2434. https://doi.org/10.1002/bdr2.2434.</p><p>In the originally published article, the Acknowledgments section omitted some names. The correct Acknowledgments section is shown below.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 5","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdr2.2478","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143896962","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}
Tonia C. Carter, Denise M. Kay, Faith Pangilinan, Lynn M. Almli, Mary M. Jenkins, Elizabeth E. Blue, Pagna Sok, Janson J. White, Christopher M. Cunniff, A. J. Agopian, Michael J. Bamshad, Lorenzo D. Botto, Lawrence C. Brody, Muge Gucsavas-Calikoglu, Jessica X. Chong, Horacio Gomez-Acevedo, Philip J. Lupo, Cynthia A. Moore, Wendy N. Nembhard, Richard S. Olney, Andrew F. Olshan, Mohammed S. Orloff, Jennita Reefhuis, Paul A. Romitti, Gary M. Shaw, Martha M. Werler, Mahsa M. Yazdy, Marilyn L. Browne, Meredith M. Howley, University of Washington Center for Mendelian Genomics, NISC Comparative Sequencing Program, the National Birth Defects Prevention Study
{"title":"Exome Sequencing to Identify Novel Susceptibility Genes for Nonsyndromic Split-Hand/Ft Malformation: A Report From the National Birth Defects Prevention Study","authors":"Tonia C. Carter, Denise M. Kay, Faith Pangilinan, Lynn M. Almli, Mary M. Jenkins, Elizabeth E. Blue, Pagna Sok, Janson J. White, Christopher M. Cunniff, A. J. Agopian, Michael J. Bamshad, Lorenzo D. Botto, Lawrence C. Brody, Muge Gucsavas-Calikoglu, Jessica X. Chong, Horacio Gomez-Acevedo, Philip J. Lupo, Cynthia A. Moore, Wendy N. Nembhard, Richard S. Olney, Andrew F. Olshan, Mohammed S. Orloff, Jennita Reefhuis, Paul A. Romitti, Gary M. Shaw, Martha M. Werler, Mahsa M. Yazdy, Marilyn L. Browne, Meredith M. Howley, University of Washington Center for Mendelian Genomics, NISC Comparative Sequencing Program, the National Birth Defects Prevention Study","doi":"10.1002/bdr2.2472","DOIUrl":"https://doi.org/10.1002/bdr2.2472","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Split-hand/foot malformation (SHFM) is a rare, genetically heterogeneous, congenital limb defect. Some but not all associated genes are known; therefore, the aim was to identify genes underlying SHFM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Buccal cell-derived DNA from 26 children with SHFM and their parents who participated in the National Birth Defects Prevention Study was exome sequenced. Family-based trio analyzes prioritized rare coding variants by inheritance patterns, predicted pathogenicity, and location within putative limb development genes. Copy-number variants in SHFM candidate genomic regions were also examined. Case–control analyzes compared coding variants between case children and 1191 controls (parents of children with non-limb birth defects). Variant validation was by Sanger sequencing or droplet digital polymerase chain reaction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In family-based analyzes, the prioritized and validated variants (each in a single family) included likely damaging variants that were heterozygous and <i>de novo</i> in speckle type BTB/POZ protein (<i>SPOP</i>) and ubiquitin-like modifier activating enzyme 2 (<i>UBA2</i>), X-linked recessive in fibroblast growth factor 13 (<i>FGF13</i>) and RNA binding motif protein 10 (<i>RBM10</i>), and compound heterozygous in interleukin enhancer binding factor 3 (<i>ILF3</i>). Validation assays did not confirm predicted <i>de novo</i> copy-number gains at chromosomes 10q24 and 19p13.11. Case–control analyzes did not identify statistically significant associations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Exome analysis nominated new susceptibility genes (<i>FGF13</i>, <i>ILF3</i>, <i>RBM10</i>, <i>SPOP</i>) and detected a variant in a known candidate gene (<i>UBA2</i>). Follow-up investigation is needed to ascertain damaging variants in these genes in additional cases with SHFM and evaluate the impact of the variants on gene expression, protein function, and limb development.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 5","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889015","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":"Domestic Use of Solvents and Pesticides and the Risk of Hypospadias in Offspring: A Case–Control Study From Brittany, France","authors":"Flore-Anne Martin, Ronan Garlantezec, Cécile Chevrier, Adèle Bihannic, Patrick Pladys, Rémi Béranger, Florence Rouget","doi":"10.1002/bdr2.2476","DOIUrl":"https://doi.org/10.1002/bdr2.2476","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>There is a growing concern about the potential role of environmental exposure in congenital male anomalies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We aimed to assess the association between the domestic use of products containing solvents or pesticides during pregnancy and the risk of hypospadias in the offspring.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included newborns from the PENEW case–control study, which took place in Brittany, France, from October 2012 to December 2018. Newborns affected with hypospadias (<i>n</i> = 100) were matched with one to four controls (<i>n</i> = 283) according to the biological sex assigned at birth, center of birth, year, and season of birth. We assessed self-reported domestic exposure to solvents (cosmetics, house cleaning, and home renovation products) and pesticides (used indoors and outdoors) through a maternal questionnaire at birth. We performed multivariable conditional logistic regression, adjusting for potential confounders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The self-reported use of indoor pesticides during pregnancy was associated with an increased risk of hypospadias in offspring (adjusted odds ratio [aOR] = 2.68, 95% CI = 1.5, 4.81), especially those against wood insects (aOR = 13.19, 95% CI = 1.11, 59.57), rodents (aOR = 4.61, 95% CI = 1.03, 20.7), and flying and crawling insects (aOR = 2.77, 95% CI = 1.46, 5.28). Other studies have shown that domestic exposure was not statistically significantly associated with a risk of hypospadias.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The use of indoor pesticides during pregnancy may be associated with a higher risk of hypospadias in offspring, especially those against flying and crawling insects. Further studies might be needed to identify specific molecules to target and confirm our results on a larger sample.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 5","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871850","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}