Birth Defects Research最新文献

{"title":"Potential Effects of Prepubertal Exposure to Perfluorooctane Sulfonic Acid on the First Wave of Folliculogenesis in Young CD-1 Mice.","authors":"Bounleut Phanavanh, Jalina Moore, Amy Inselman, Xiaoqing Li, Kyung Sung, Pei-Hsuan Hung, Li You, Noriko Nakamura","doi":"10.1002/bdr2.70052","DOIUrl":"10.1002/bdr2.70052","url":null,"abstract":"<p><strong>Background: </strong>Perfluorooctane sulfonic acid (PFOS) belongs to a group of synthetic chemicals referred to as per- and polyfluoroalkyl substances (PFAS) that are known to degrade slowly. Exposure to PFOS has been reported to cause birth defects and disrupt female sex hormone levels in mice. However, to date, the direct effects of PFOS exposure on folliculogenesis in young animals have not been evaluated. Therefore, this study was conducted to examine the potential effects of in utero and prepubertal exposure to PFOS on follicle development in juvenile, female mouse pups.</p><p><strong>Methods: </strong>ICR dams and young, female mouse pups were dosed with 0.1 mg/kg PFOS or saline (vehicle) via gavage beginning on gestation day (GD) 6 (plug positive = GD 0) through GD 17 (n = 11-17 per group) [in utero exposure] or postnatal day (PND) 7 (PND 0 = day of birth) through PND 21 (n = 22-29 per group) [prepubertal exposure]. Ovaries and blood were then collected from a pup/litter on PND 28 for analysis.</p><p><strong>Results: </strong>There were no adverse effects of PFOS exposure observed in the measured endpoints upon in utero exposure; however, statistically significant differences following prepubertal exposure were noted for serum estradiol levels, the total number of primordial follicles, and the transcript levels of Foxo1 and Gdf9.</p><p><strong>Conclusion: </strong>The preliminary findings suggest that prepubertal exposure to PFOS may affect follicle development by disrupting estradiol production and altering Foxo1 and Gdf9 gene expression. Further studies will be important to examine the mechanisms underlying prepubertal exposure to PFOS on folliculogenesis.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 5","pages":"e70052"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perinatal Development: Misunderstood Biology That Can Lead Hazard Assessment Astray.","authors":"John M DeSesso","doi":"10.1002/bdr2.70061","DOIUrl":"10.1002/bdr2.70061","url":null,"abstract":"<p><strong>Background: </strong>Gestation periods of rodents and humans differ dramatically. Due to their brief time in utero, rodent offspring develop faster than humans, but at birth they are considerably less developmentally mature than human neonates. Because fetuses are harvested near-term in embryo-fetal development studies, some fetuses which lag others in developmental schedules may be characterized as malformed. However, if allowed to continue, many deficits in developmental timing would be eliminated quickly during the early lactational period. Consequently, it is important to appreciate the perinatal development of test species to inform interpretation of test results.</p><p><strong>Methods: </strong>This paper reviews the comparative timing as well as pre and postnatal development of exemplar organs for the purpose of providing context in interpreting rodent data and extrapolating them to human hazard assessment. The selected organs and developmental processes include ossification of the skeleton; septation of the cardiac atria and ventricles; surfactant synthesis in the lung; establishment of the intestinal lining and maturation of gastrointestinal absorption; myelination of the brain and establishment of the blood-brain barrier.</p><p><strong>Results: </strong>Comparative perinatal biology should be used in interpreting rodent test data to avoid mis-classifying substances. Due to the compressed development schedule of rodents compared with humans, delays in rodent development may be misinterpreted as malformations. Delays in lung maturation may explain some cases of early deaths in normally appearing rat pups. Invoking perinatal biology does not obviate study findings, but it can provide context that informs interpretation.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 5","pages":"e70061"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970361","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":"Sirenomelia: A Review of European Prevalence Data and Epidemiological Analysis of 17 Cases Registered in Wales.","authors":"Chris Emmerson, Michael Olson, Ceri Williams, Robert Maddison, David Tucker, Llion Davies, Annie Perraud, Linda Bailey, Ciarán Humphreys, Rhian Hughes, Joanna Sichitiu, Madalen Oribe Amores, Ingeborg Barisic, Michele Santoro, Clara Cavero Carbonell, Elizabeth S Draper, Martin Haeusler, Isabelle Monier, Anna Latos-Bielenska, Carlos Matias Dias, Elly Den Hond, Elisa Ballardini, Mary O'Mahony, Isabelle Perthus, Judith Rankin, Anke Rissmann, Florence Rouget, Sarah Stevens, Jorieke E H Bergman, Diana Wellesley, Wladimir Wertelecki","doi":"10.1002/bdr2.70051","DOIUrl":"10.1002/bdr2.70051","url":null,"abstract":"<p><strong>Background: </strong>Sirenomelia is a rare congenital condition most notably characterized by a single lower limb. Previous studies have suggested a prevalence of approximately 1 per 100,000 births. However, in Wales 17 cases were recorded between 1998 and 2016, suggesting a higher rate of sirenomelia in this country.</p><p><strong>Objectives: </strong>This study compared current prevalence of sirenomelia in Wales with European data. This study further reviewed detailed time, place, and person data on sirenomelia cases in Wales to investigate possible causal factors.</p><p><strong>Method: </strong>A retrospective cohort study from birth defect surveillance programs. Individual-level records for all welsh cases were examined for evidence of causal factors. Comparator data from other countries were obtained from EUROCAT (a European network of population-based registries for the epidemiological surveillance of congenital anomalies).</p><p><strong>Results: </strong>European data from 24 national and regional registries of congenital anomalies included 97 cases of sirenomelia identified across 9.6 million births between 1998 and 2016, giving a prevalence rate of 1 per 100,000 (95% CI 0.83, 1.23). Five regions reported statistically significantly higher rates than that recorded across all registries, while one region reported a significantly lower rate. Small numbers of cases limit definitive statistical interpretation. Analysis of the Wales data did not identify common epidemiological factors between cases.</p><p><strong>Conclusions: </strong>The contemporary prevalence of sirenomelia across Europe is consistent with earlier studies at approximately 1 per 100,000 births (95% CI 0.83, 1.23). However, there is greater variation between regions than would be expected by chance. There remains no definitive evidence for causal environmental factors.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 5","pages":"e70051"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal Fish Intake in the Year Prior to Conception and Birth Defects, National Birth Defects Prevention Study, 1997-2011.","authors":"Dorothy Kim Waller, Zeyu Miao, Renata H Benjamin, Richard Finnell, Nithya Lakshmi Mohan Dass, Eirini Nestoridi, Marcia C de Oliveira Otto, Julie Peterson, Tunu Ramadhani, Mark A Canfield","doi":"10.1002/bdr2.70053","DOIUrl":"10.1002/bdr2.70053","url":null,"abstract":"<p><strong>Background: </strong>Epidemiologic data on the association between maternal fish intake and birth defects are sparse. Our objective was to assess associations between maternal fish intake and 52 different birth defects, most of which have not been assessed previously.</p><p><strong>Methods: </strong>Using logistic regression, data was analyzed for 29,242 mothers of infants with birth defects and 10,973 mothers of control infants who participated in the National Birth Defects Prevention Study (NBDPS) and delivered between 1997 and 2011. We focused on associations between mothers who reported high fish intake of 2 or more servings of fish per week for the year prior to conception versus those who reported little or no fish intake and 52 birth defects. Each birth defect was analyzed separately.</p><p><strong>Results: </strong>Among control mothers, 13.9% reported high fish intake and 31.3% reported eating very little or no fish. High fish intake was associated with lower odds of 9 birth defects (isolated heterotaxia, double outlet right ventricle transposition of the great arteries, total anomalous pulmonary venous return, Dandy Walker syndrome, holoprosencephaly, choanal atresia, cleft palate, craniosynostosis, and gastroschisis) with adjusted odds ratios (aORs) ranging from 0.32 to 0.83. An elevated association with high fish intake was observed for one birth defect (tricuspid atresia, aOR = 1.76; 95% CI 1.07, 2.89).</p><p><strong>Conclusion: </strong>Based on our findings, consumption of 2 or more servings of fish per week may help to prevent certain types of birth defects. This conclusion is similar to the existing FDA (Food and Drug Administration) recommendation that women who are or can become pregnant should consume 2-3 servings of low mercury seafood per week. A large majority of pregnant women in this US (United States) based study did not meet the FDA recommendations for fish intake, suggesting that many of them may have benefited from increasing their consumption of seafood.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 5","pages":"e70053"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural Tube Defects (NTDs) and Modifiable Maternal Behavioral Risks in a Low-Resource Setting: Evidence From a Multicenter, Hospital-Based, Case-Control Study in Ethiopia.","authors":"Rahel T Asrat, Abel Gedefaw, Tafese Bosha, Andrew J Copp","doi":"10.1002/bdr2.70055","DOIUrl":"10.1002/bdr2.70055","url":null,"abstract":"<p><strong>Background: </strong>Neural tube defects (NTDs) are among the most common and severe congenital anomalies, with an especially high prevalence in Ethiopia. This study aimed to identify potential maternal risk and protective factors associated with NTDs in a low-resource African setting.</p><p><strong>Methods: </strong>A multicenter, hospital-based, matched case-control study was conducted in Hawassa and Addis Ababa, in which cases were mothers of live born, stillborn, or electively terminated pregnancies after 12 weeks of gestation with an established NTD in the fetus or infant. Controls were pregnant and postpartum women whose pregnancy did not involve an NTD. The data collection tool included: maternal socio-demographic factors, reproductive histories, and current pregnancy-related and behavioral characteristics. Bivariate and multivariate conditional logistic regression analysis was performed to estimate adjusted odds ratios (AOR) and 95% confidence intervals.</p><p><strong>Results: </strong>Significant associations with NTDs include: khat (Catha edulis) chewing during pregnancy (AOR: 3.214; 95% CI: 1.53-6.75), maternal alcohol intake (AOR: 3.017; 95% CI: 1.57-5.79), and high coffee consumption (more than three cups per day) (AOR: 2.46; 95% CI: 1.35-4.46). Also, industry working (AOR: 10.03; 95% CI: 2.16-46.64) and nulliparity (AOR: 2.06; 95% CI: 1.14-3.72) were significantly associated with NTDs. Folic acid/multivitamin supplementation had a strong protective effect when taken a month before conception (AOR: 0.18; 95% CI: 0.04-0.81), and to a lesser extent when taken after conception (AOR: 0.51; 95% CI: 0.31-0.85).</p><p><strong>Conclusion: </strong>In the high-prevalence setting of Ethiopia, maternal behavioral factors such as khat chewing, alcohol intake, and excessive coffee consumption are significantly associated with increased risk of NTDs, suggesting possible teratogenic effects. Folic acid supplementation, particularly when started before conception, is a strong protective factor.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 5","pages":"e70055"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873360","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":"How Epigenetics Bridges Genes and Environment: A Multiomics Evidence Chain in Congenital Diaphragmatic Hernia.","authors":"Yunshan Gao, Xian Zhu, Rutao Dai, Xichen Zhang, Yongyu Ma, Ya Dao, Junru Chen, Shiwu Yang, Jun Wu","doi":"10.1002/bdr2.70047","DOIUrl":"10.1002/bdr2.70047","url":null,"abstract":"<p><strong>Background/objectives: </strong>Congenital diaphragmatic hernia (CDH) is a severe developmental anomaly with high etiological heterogeneity. Although numerous susceptibility genes have been identified, genetic factors alone fail to explain the full disease risk. Epidemiological data highlight the contribution of environmental exposures. Epigenetic regulation provides a crucial link bridging genetic predisposition and environmental influence. This review aims to summarize recent multiomics evidence elucidating how epigenetic mechanisms mediate gene-environment interactions in CDH.</p><p><strong>Methods: </strong>This narrative review summarizes studies published over the past decade on epigenetic mechanisms in congenital diaphragmatic hernia (CDH), including DNA methylation, histone modifications, noncoding RNAs, and integrative genomic and transcriptomic analyses in human samples, animal models, and iPSC-derived organoids. Relevant literature was identified through targeted searches of the biomedical literature and screening of reference lists from key articles. Relevant studies were considered according to their relevance to epigenetic regulation, gene-environment interactions, and translational implications in CDH.</p><p><strong>Results: </strong>Aberrant DNA methylation, histone acetylation imbalance, and dysregulated miRNAs converge on key developmental pathways, including retinoic acid, TGF-β, and NF-κB signaling. Experimental evidence shows that miR-200b supplementation or pharmacological restoration of histone acetylation can partially rescue pulmonary hypoplasia in nitrofen-induced CDH models. iPSC and organoid systems further demonstrate synergistic effects between genetic susceptibility and mechanical stress, supporting epigenetic regulation as a mechanistic bridge.</p><p><strong>Conclusions: </strong>Epigenetic mechanisms serve as core mediators linking genetic and environmental factors in CDH pathogenesis. Future directions include large-scale EWAS/WGBS and multiomics integration, establishment of standardized epigenetic databases, and ethically guided development of prenatal epigenetic diagnostics and targeted interventions.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 5","pages":"e70047"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13169189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probing the Biological Plausibility of Fluoride as an Endocrine Disruptor.","authors":"Ashley M Mudd, Bladimir J Ovando, George P Daston","doi":"10.1002/bdr2.70046","DOIUrl":"10.1002/bdr2.70046","url":null,"abstract":"<p><strong>Background: </strong>Fluoride has come under recent scrutiny regarding concerns over potential neurodevelopmental and endocrine-related toxicities, with recent reviews by the National Toxicology Program (NTP) and European Food Safety Authority (EFSA) concluding with moderate or reasonable confidence, respectively, that exposure to drinking water having greater than 1.5 mg fluoride/L is associated with lower IQ in children. A key outcome of these reviews is the uncertainty regarding the biological plausibility of these findings. However, it has been hypothesized that endocrine disruption could be a potential factor.</p><p><strong>Methods: </strong>To determine if sodium fluoride exerts direct biological activity on molecular and cellular targets related to endocrine disruption, receptor binding and activity assays of thyroid and other hormone-related targets, H295R steroidogenesis, and sodium-iodide symporter (NIS) assays were carried out using exposures comparable to or in excess of those that have been reported to be associated with neurodevelopmental outcomes and other effects.</p><p><strong>Results: </strong>Sodium fluoride at up to 316 μM NaF did not affect synthesis of estrogen or testosterone. Sodium fluoride at up to 10 μM NaF did not interact with aromatase, steroid 5 alpha-reductase, estrogen receptors, androgen receptors, thyroid hormone receptors, nor did it inhibit thyroid peroxidase. Furthermore, there were no changes in iodide uptake via symporter transport (up to 300 μM NaF). Other endocrine targets were also evaluated at 10 μM NaF, including PR, PPARα, PPARγ, AhR, CAR, PXR, RARα, or GR, and no binding was observed either.</p><p><strong>Conclusions: </strong>Together, the results from this series of experiments demonstrate an absence of effects of fluoride on endocrine disruption targets at concentrations comparable to or in excess of exposures reported in the literature to be associated with neurodevelopmental outcomes and other effects.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 5","pages":"e70046"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13177271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147939593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Approach Methodologies and Open Access Tools Help Characterize Risks for DART, DNT, or Endocrine Effects From Exposure to Hallucinogens With Potential Pesticide Contaminants.","authors":"Marilyn H Silva","doi":"10.1002/bdr2.70048","DOIUrl":"10.1002/bdr2.70048","url":null,"abstract":"<p><strong>Background: </strong>Psilocybe mushrooms (psilocybin/psilocin [PSI/PSC]) and ayahuasca (N,N-dimethyltryptamine [DMT]) are hallucinogenic serotonergic agonists. Pregnant and lactating women are frequently omitted from clinical studies; hence minimal developmental/reproductive/neurotoxicity (DART/DNT) and endocrine disruption (ED) data in humans are available. Hallucinogens contaminated with pesticides may have overlapping metabolic pathways affecting toxicity. An examination of potential adverse effects on pregnancy and development from exposure to hallucinogenic plants, hypothetically contaminated with organophosphates (OP) or organochlorines (OC), was performed using new approach methodologies (NAMs) and open access tools.</p><p><strong>Methods: </strong>Cheminformatics Modules, Predicting Developmental Toxicity Potential Project, Toxicity Estimation Software Tool (TEST) using quantitative structure-activity relationships, Endocrine Disruptor Screening Program, California's Proposition 65 list, and ToxCast assays were investigated for DART/DNT and ED reported effects and/or predictions related to PSI/PSC, DMT, and sentinel pesticides (chlorpyrifos/chlorpyrifos-oxon and endosulfan). ToxCast data were inputs for Integrated Chemical Environment (ICE) PBTK adult and fetal models to generate adjusted human Administered Equivalent Doses (AdjAEDs) that were compared to regulatory dose ranges for hallucinogens and pesticides to assess model predictions.</p><p><strong>Results: </strong>Cheminformatics Modules, PregPred, and TEST-QSAR predicted that hallucinogens and pesticides have DART, DNT, and ED effects. No ToxCast data were reported for DMT and PSI was ToxCast inactive. PSC/pesticide overlapping metabolic pathways were CYP2C9 modulated by serotonin, thyroid hormones and sonic hedgehog, each associated with development. Clinical PSC and regulatory pesticide points of departure were generally within range of predicted fetal AdjAEDs.</p><p><strong>Conclusions: </strong>Open access NAMs tools identified risks to fetal development from exposure to hallucinogens and pesticides.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 5","pages":"e70048"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980504","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":"Teratogenic Effect of OROV Infection: An Analysis of Its Causality.","authors":"María Paz Bidondo, Paloma Brun, Boris Groisman, Marianela Trotta, Pablo Barbero","doi":"10.1002/bdr2.70062","DOIUrl":"10.1002/bdr2.70062","url":null,"abstract":"<p><p>Oropouche virus (OROV) is an arbovirus that has caused multiple epidemic outbreaks in several Latin American countries. In 2024, cases of possible vertical transmission with congenital microcephaly were reported, raising concerns about potential teratogenic effects. However, the causal relationship between OROV infection during pregnancy and congenital anomalies remains poorly defined. This study aimed to analyze the evidence on the potential teratogenic effect of OROV in humans through a systematic literature review, applying Shepard's criteria for causality. The available evidence supports a temporal relationship between exposure during critical periods of prenatal development and observed effects in offspring. Reported cases share certain common characteristics that could suggest a specific syndrome. Experimental studies in animal models demonstrate vertical transmission of OROV and harmful effects in offspring. Considering the documented vertical transmission, viral presence in the central nervous system, and known pathogenic mechanisms, biological plausibility exists for a teratogenic effect. However, no epidemiological study has yet evaluated the association between OROV infection and teratogenicity. Furthermore, given that infection occurs during epidemic outbreaks rather than through sporadic environmental exposure, the criterion of infrequent exposure associated with an infrequent defect is not met. Therefore, Shepard's teratogenicity criteria are not yet fully fulfilled. In conclusion, while suggestive evidence exists, definitive proof of OROV teratogenicity remains lacking. Health authorities should prioritize research initiatives, strengthen epidemiological surveillance groups, ensure availability of serological testing for OROV infection, and enhance congenital defect surveillance systems to better characterize this potential association.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 5","pages":"e70062"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970392","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":"Ontogeny of Placental FcRn Protein During Human and Animal Pregnancy to Inform Developmental Toxicity Testing.","authors":"Christopher J Bowman, William J Breslin, Connie Chen, Warren Foster, Julia Hui, Beata Kusmider, Susan Laffan, Matt Myers, Lakshmi Sivaraman, Belen Tornesi, Susan Westmoreland, John M DeSesso","doi":"10.1002/bdr2.70058","DOIUrl":"10.1002/bdr2.70058","url":null,"abstract":"<p><strong>Introduction: </strong>Species differences exist in Fc domain-containing molecule transfer/biodistribution to the embryo-fetus during pregnancy. Placentation was reviewed and placental neonatal Fc receptor (FcRn) quantitation in the chorioallantoic placenta (CAP) and/or inverted yolk sac placenta (InvYSP) was investigated across species throughout gestation to further understand and inform developmental toxicity testing of Fc domain-containing molecules.</p><p><strong>Methods: </strong>Quantitative mass spectrometry was used to quantify FcRn protein in CAP and/or InvYSP throughout gestation in mouse, rat, guinea pig, rabbit, and nonhuman primate (NHP). In human placental tissues, immunohistochemistry was used to localize FcRn distribution during each trimester.</p><p><strong>Results: </strong>FcRn protein was detected and concentration increased throughout gestation in mouse, rat, guinea pig, and rabbit; with InvYSP concentration markedly higher compared with CAP at all gestational ages. In contrast, NHP FcRn protein concentration in the CAP remained constant throughout gestation. In humans, during 1st trimester, FcRn occurred in decidua, maternal endothelium, and maternal and fetal macrophages. During 2nd trimester, fetal FcRn increased in syncytiotrophoblasts and fetal chorionic vessels. FcRn expression decreased in maternal endothelium near term.</p><p><strong>Conclusions: </strong>FcRn protein was detected throughout gestation (including organogenesis) in placental tissue of all animal species. Regardless of FcRn location, these data support that Fc domain-containing molecules can access the embryo-fetus throughout gestation in all species, with the extent of transfer likely depending on FcRn concentration and size of the placenta. This information on placental FcRn ontogeny will help improve study design and translation of nonclinical developmental toxicity data to human safety assessment of Fc domain-containing molecules.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 5","pages":"e70058"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13176392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147939571","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}