Aorta Without Coronary Arteries: Anatomic Variants of a Rare Malformation.

Absence of connection of both coronary arteries to the aorta is an extremely rare congenital malformation. Most cases reported are anatomic variants of anomalous left coronary artery to pulmonary artery, found in isolation or in association with other congenital heart defects. We describe here four cases of patients born without any coronary artery connected to the aorta, including two with an almost complete absence of epicardial coronary arteries, one with single coronary artery to the right pulmonary artery, and one with left ventricular connection of a single coronary artery. Those exceptional coronary malformations have a poor prognosis and are often diagnosed at autopsy. Total absence of epicardial coronary arteries, present in two of our patients and described only once in the literature, leads us to reconsider current knowledge of human coronary artery development.

Exon skip-inducing variants in FLNA in an attenuated form of frontometaphyseal dysplasia.

Pathogenic variation in the X-linked gene FLNA causes a wide range of human developmental phenotypes. Loss-of-function is usually male embryonic-lethal, and most commonly results in a neuronal migration disorder in affected females. Gain-of-function variants cause a spectrum of skeletal dysplasias that present with variable additional, often distinctive, soft-tissue anomalies in males and females. Here we present two, unrelated, male individuals with novel, intronic variants in FLNA that are predicted to be pathogenic. Their phenotypes are reminiscent of the gain-of-function spectrum without the skeletal manifestations. Most strikingly, they manifest urethral anomalies, cardiac malformations, and keloid scarring, all commonly encountered features of frontometaphyseal dysplasia. Both variants prevent inclusion of exon 40 into the FLNA transcript, predicting the in-frame deletion of 42 amino acids, however the abundance of FLNA protein was equivalent to that observed in healthy individuals. Loss of these 42 amino acids removes sites that mediate key FLNA functions, including binding of some ligands and phosphorylation. This phenotype further expands the spectrum of the FLNA filaminopathies.

Cardiac manifestations in a western moyamoya disease population: a single-center descriptive study and review.

An embryological association between moyamoya disease (MMD) and cardiac manifestations has been proposed. Data up to this point remains anecdotal, and the prevalence of cardiac manifestations in a western MMD population is uncertain. The objective of this study was to determine the prevalence of cardiac manifestations including coronary artery disease (CAD) and congenital cardiac defects in a mostly Caucasian population of MMD patients and review prior reports of such cases. Medical records of MMD patients who presented to our institution between 1990 and 2019 were retrospectively reviewed for the presence of various congenital cardiac malformations and concomitant CAD. The prevalence of congenital cardiac defects and CAD was determined. A literature search for prior cases of MMD with concomitant cardiac manifestations was performed. A total of 181 MMD patients were included in our analysis, 139 (76.8%) of whom were Caucasian. Ten patients had cardiac manifestations (5.5%). There were six total MMD patients with congenital cardiac defects (3.3%). All patients with congenital defects were diagnosed in childhood. The prevalence of congenital defects in MMD was slightly higher than the general population as reported previously (0.8-1.2%). Four MMD patients had CAD (2.2%). The mean age of patients with CAD was 41.0 years (SD = 12.3, range = 33-59) in our series and 33.1 years (SD = 15.0) in a review of prior reports. These mean ages of CAD are in contrast to the 7th and 8th decades of lifein the general population as indicated by prior studies. Our findings support an association between MMD and cardiac manifestations. Further investigation is warranted in order to further characterize this potential relationship and shed light on a possible cardio-cephalic neural crest syndrome.

First-trimester ductus venosus velocity ratio as a marker of major cardiac defects.

OBJECTIVES: To examine ductus venosus (DV) flow in fetuses with and those without a cardiac defect and to evaluate different phases of DV flow in addition to the standard assessment of DV pulsatility index for veins (PIV) and the a-wave. METHODS: This was a retrospective study of singleton pregnancies that underwent first-trimester ultrasound screening, which included DV flow assessment, at the University of Tübingen (between 2010 and 2017) or the University of Cologne (between 2013 and 2016). The study population comprised normal fetuses and fetuses with major cardiac defects at a ratio of 10:1. For each fetus, the following parameters of the DV waveform were evaluated: qualitative assessment of the a-wave, PIV measurement and ratios of flow velocities during the S-wave (S) or D-wave (D) and the a-wave (a) or v-wave (v). Reproducibility of DV-PIV and DV flow ratios was evaluated in 30 fetuses in which the DV flow was assessed twice. RESULTS: Our study population included 480 anatomically normal fetuses and 48 with a cardiac defect. Median fetal nuchal translucency (NT) in the normal and in the affected group was 1.9 mm and 2.6 mm, respectively. In five (1.0%) of the normal and 18 (37.5%) of the affected cases, fetal NT thickness was above the 99th centile. In the normal group, the DV a-wave was reversed in 15 (3.1%) cases and the DV-PIV was above the 95th centile in 25 (5.2%). In the cases with cardiac defects, the a-wave was reversed and the DV-PIV measurement was above the 95th centile in 26 (54.2%). The reproducibility of measurement of the ratios of DV flow velocities was similar to that of the DV-PIV. Most cardiac defects were associated with an abnormal a/S or a/D ratio. If the cut-off for these two ratios was set at the 5th centile of the normal distribution, the detection rate of fetal cardiac anomalies would be 62.5%. This compares favorably with the DV-PIV, which detects 26 (54.2%) of the affected fetuses for the same threshold. CONCLUSION: In the first trimester, the a/S ratio has the potential to detect approximately 60% of congenital cardiac defects for a false-positive rate of 5%. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

[Relevant aspects of the ESC guidelines for the management of cardiovascular diseases during pregnancy for obstetric anaesthesia (update 2018)]. / Anästhesiologisch relevante Aspekte der ESC-Leitlinien für das Management von kardiovaskulären Erkrankungen während der Schwangerschaft (Update 2018).

The current update of the ESC (European Society of Cardiology) guidelines on managing cardiovascular diseases during pregnancy provides instructions for doctors in daily practice. Heart diseases are the most common reason for maternal death during pregnancy in western countries. Among other things, the following topics are dealt with: congenital heart disease, pulmonary hypertension, aortic and valvular diseases as well as arrhythmias and hypertensive disorders. Compared to the guidelines from 2011 some changes have been made regarding the recommendations to classify maternal risk according to the modified World Health Organization (mWHO) classification or in recommendations on anticoagulation for low-dose and high-dose requirements of vitamin K antagonists. The main focus of this summary of recent recommendations is the impact on the anesthesia management in order to provide responsible anesthesiologists with relevant background knowledge.

Silencing mutations in JAG1 gene may play crucial roles in the pathogenesis of Tetralogy of Fallot.

JAG1 gene through Notch signaling is implicated in cell fate decisions in early cardiac development, and mutations in several proteins in the pathway have been involved in various disorders. Tetralogy of Fallot (TOF) is the most frequent form of complicated congenital heart disease. The abnormality of TOF begins through the first eight weeks of fetal growth and is confused with ventricular septal defects, obstruction to right ventricular outflow tract, aortic dextroposition, and right ventricular hypertrophy. Hence the existence of mutations in JAG1 gene in Iranian patients with TOF is evaluated. The clinical data and peripheral blood samples were collected from 44 sporadic nonsyndromic patients with TOF and compared to 44 healthy individuals. DNA was extracted, and the exon 6 of the JAG1 gene was amplified by PCR then the PCR products were purified and sequenced. The age range in patients and the control group was 2-36 years, and the mean and standard deviation (SD) of the age in patients was (11.69 ± 7.85 years) and in control group (11.63 ± 7.99 years).  Finally, the samples were successfully sequenced, then analyzed and one synonymous variant (c.765C>T; p.Y255Y) was observed in 38 patients with frequency (86.4%) and three controls with frequency (6.8%). The c.765C>T variant is significantly associated with the pathogenesis of TOF in Iranian population.

Use of antibiotics during pregnancy and the risk of major congenital malformations: a population based cohort study.

AIMS: Few studies have investigated the link between individual antibiotics and major congenital malformations (MCMs) including specific malformations owing to small sample size. We aimed to quantify the association between exposure to gestational antibiotic and the risk of MCMs. METHODS: Using the Quebec pregnancy cohort (1998-2008), we included a total of 139 938 liveborn singleton alive whose mothers were covered by the "Régie de l'assurance maladie du Québec" drug plan for at least 12 months before and during pregnancy. Antibiotic exposure was assessed in the first trimester and MCMs were identified within the first year of life. RESULTS: After adjusting for potential confounders, clindamycin exposure was associated with an increased risk of MCMs (aOR 1.34, 95% CI 1.02-1.77, 60 exposed cases), musculoskeletal system malformations (aOR 1.67, 95% CI 1.12-2.48, 29 exposed cases) and ventricular/atrial septal defect (aOR 1.81, 95% CI 1.04-3.16, 13 exposed cases). Doxycycline exposure increased the risk of circulatory system malformation, cardiac malformations and ventricular/atrial septal defect (aOR 2.38, 95% CI 1.21-4.67, 9 exposed cases; aOR 2.46, 95% CI 1.21-4.99, 8 exposed cases; aOR 3.19, 95% CI 1.57-6.48, 8 exposed cases, respectively). Additional associations were seen with quinolone (1 defect), moxifloxacin (1 defect), ofloxacin (1 defect), macrolide (1 defect), erythromycin (1 defect) and phenoxymethylpenicillin (1 defect). No link was observed with amoxicillin, cephalosporins and nitrofurantoin. Similar results were found when penicillins were used as the comparator group. CONCLUSIONS: Clindamycin, doxycycline, quinolones, macrolides and phenoxymethylpenicillin in utero exposure were linked to organ-specific malformations. Amoxicillin, cephalosporins and nitrofurantoin were not associated with MCMs.

Congenital pseudoaneurysm of the mitral-aortic intervalvular fibrosa: a case report.

The mitral-aortic intervalvular fibrosa is an area of fibrous continuity between the mitral and aortic valves. We present the first case of a congenital pseudoaneurysm in this region, detected prenatally as an isolated cardiac defect, which was followed-up conservatively postnatally. The diagnosis was confirmed by echocardiogram demonstrating blood flow into the pouch during systole and into the left ventricular outflow tract during diastole. The infant has been followed-up with serial echocardiograms demonstrating stable size and appearance of the lesion, without signs of obstruction, making close continued observation a reasonable approach.

ALCAPA Syndrome and Atrial Septal Defect In a 68-Year-Old Woman: An Extremely Rare Congenital Association.

Anomalous left coronary artery arising from the pulmonary artery (ALCAPA) has been generally reported as an isolated lesion that is also called Bland-White-Garland syndrome. Herein we report a case of ALCAPA syndrome with an atrial septal defect in a 68-year-old woman. She had been asymptomatic until the age of 68. Echocardiographic examination revealed atrial septal defect, and coronary angiography showed that the left main coronary artery originated from the pulmonary artery and intensive collateral connections between the right and left coronary artery. In this case, it would appear that ALCAPA is associated with atrial septal defect.

Ellis-van Creveld with an Unusual Dental Anomaly: A Case Report.

The Ellis-van Creveld (EVC) syndrome is a chondroectodermal dysplasia and is characterized by the cardinal features of disproportionate short stature, polydactyly, hidrotic ectodermal dysplasia, and congenital heart malformations, along with other skeletal and dental abnormalities. It is a rare condition, with very few cases reported in the medical literature. It is inherited as an autosomal recessive disorder with variable expressions, due to the mutation of the EVC syndrome 1 and 2 genes, which are located on chromosome 4p16. The present case report describes the EVC syndrome in a 14-year-old girl, who presented with a tetrad of all the cardinal features and other associated features. Additional unusual dental findings such as single-rooted funnel-shaped molars, reduced crown size, enamel hypoplasia, supernumerary teeth, dental fusion, taurodontism, abnormal occlusal anatomy with wide grooves, and atypical cusps have been reported in most previous cases of this syndrome. However, in our patient, surprisingly, the teeth present were relatively non-anomalous, both clinically and radiographically (i.e., with none of the usually found abnormalities mentioned above). The only abnormal dental findings were those of absent maxillary and mandibular incisors (including impacted permanent incisors) and mild malocclusion, a novel point of this case.

Interstitial deletion of 7q22.1q31.1 in a boy with structural brain abnormality, cardiac defect, developmental delay, and dysmorphic features.

This report describes a male child with a history of poor feeding and swallowing problems, hypotonia, mild bilateral sensorineural hearing loss, cerebral cortical agenesis, cardiac defects, cyanotic episodes triggered by specific movement, dysmorphic features, and developmental delays. Analysis by CytoScan HD array identified a 12.1 Mb interstitial deletion of 7q22.1q31.1 (98,779,628-110,868,171). We present a comprehensive review of the literature surrounding intermediate 7q deletions that overlap with this child's deletion, and an analysis of candidate genes in the deleted region. © 2016 Wiley Periodicals, Inc.

Nkx2-5 suppresses the proliferation of atrial myocytes and conduction system.

RATIONALE: Tight control of cardiomyocyte proliferation is essential for the formation of four-chambered heart. Although human mutation of NKX2-5 is linked to septal defects and atrioventricular conduction abnormalities, early lethality and hemodynamic alteration in the mutant models have caused controversy as to whether Nkx2-5 regulates cardiomyocyte proliferation. OBJECTIVE: In this study, we circumvented these limitations by atrial-restricted deletion of Nkx2-5. METHOD AND RESULTS: Atrial-specific Nkx2-5 mutants died shortly after birth with hyperplastic working myocytes and conduction system including two nodes and internodal tracts. Multicolor reporter analysis revealed that Nkx2-5-null cardiomyocytes displayed clonal proliferative activity throughout the atria, indicating the suppressive role of Nkx2-5 in cardiomyocyte proliferation after chamber ballooning stages. Transcriptome analysis revealed that aberrant activation of Notch signaling underlies hyperproliferation of mutant cardiomyocytes, and forced activation of Notch signaling recapitulates hyperproliferation of working myocytes but not the conduction system. CONCLUSIONS: Collectively, these data suggest that Nkx2-5 regulates the proliferation of atrial working and conduction myocardium in coordination with Notch pathway.

3D Visualization of Developmental Toxicity of 2,4,6-Trinitrotoluene in Zebrafish Embryogenesis Using Light-Sheet Microscopy.

Environmental contamination by trinitrotoluene is of global concern due to its widespread use in military ordnance and commercial explosives. Despite known long-term persistence in groundwater and soil, the toxicological profile of trinitrotoluene and other explosive wastes have not been systematically measured using in vivo biological assays. Zebrafish embryos are ideal model vertebrates for high-throughput toxicity screening and live in vivo imaging due to their small size and transparency during embryogenesis. Here, we used Single Plane Illumination Microscopy (SPIM)/light sheet microscopy to assess the developmental toxicity of explosive-contaminated water in zebrafish embryos and report 2,4,6-trinitrotoluene-associated developmental abnormalities, including defects in heart formation and circulation, in 3D. Levels of apoptotic cell death were higher in the actively developing tissues of trinitrotoluene-treated embryos than controls. Live 3D imaging of heart tube development at cellular resolution by light-sheet microscopy revealed trinitrotoluene-associated cardiac toxicity, including hypoplastic heart chamber formation and cardiac looping defects, while the real time PCR (polymerase chain reaction) quantitatively measured the molecular changes in the heart and blood development supporting the developmental defects at the molecular level. Identification of cellular toxicity in zebrafish using the state-of-the-art 3D imaging system could form the basis of a sensitive biosensor for environmental contaminants and be further valued by combining it with molecular analysis.

Existence of mutations in the homeodomain-encoding region of NKX2.5 gene in Iranian patients with tetralogy of Fallot.

BACKGROUND: Tetralogy of Fallot (TOF), the most common cyanotic heart defect and one of the most common congenital heart diseases, occurs mostly sporadically and nonsyndromically. The underlying molecular genetic mechanism is not known. Therefore, the existence of mutations in the homeodomain-encoding region of NKX2.5 gene in Iranian patients with tetralogy of Fallot is evaluated. MATERIALS AND METHODS: In the present study, we analyzed the peripheral blood samples of27 patients in order to find any mutation in the 180 bp homeodomain-encoding region of NKX2.5 gene, which is known to be involved in heart development and diseases. DNA was extracted and all the samples were amplified by polymerase chain reaction (PCR) and sequenced. RESULTS: Twenty-seven patients were included in the study. Twenty-five of them were infants and children (6 days to 11 years of age), one was a teenager (14-years of age), and another was a 33-year-old man [mean ± standard deviation (SD): 5.80 ± 3.90 years]. Thirteen patents were males (mean ± SD: 6.587077 ± 5.02 years) and 14 were females (mean ± SD: 5.0726 ± 2.81 years). One synonymous variant, i.e., c.543G>A was identified in one patient. CONCLUSION: Mutations in the homeodomain-encoding region of NKX2.5 gene may not have an outstanding role in etiology of tetralogy of Fallot patients in Iran.

Sertraline use during pregnancy and the risk of major malformations.

OBJECTIVE: Given the current debate and growing public concerns on selective serotonin reuptake inhibitors (SSRIs) and birth defects generated by Food and Drug Administration warnings, we aim to quantify the association between first-trimester exposure to sertraline, a first-line treatment, and the risk of congenital malformations in a cohort of depressed women. STUDY DESIGN: This was a population-based cohort study in Quebec, Canada, 1998 through 2010. From a cohort of 18,493 depressed/anxious pregnancies, sertraline-exposed, nonsertraline SSRI-exposed, non-SSRI exposed, and unexposed (reference category) women were studied. Major malformations overall and organ-specific malformations in the first year of life were identified. Generalized estimating equation models were used to obtain risk estimates and 95% confidence intervals (CIs). Analyses were adjusted for potential confounders. RESULTS: Among the 18,493 eligible pregnancies, 366 were exposed to sertraline, 1963 to other SSRIs, and 1296 to non-SSRI antidepressants during the first trimester of pregnancy. Sertraline use was not statistically significantly associated with the risk of overall major malformations when compared to nonuse of antidepressants. However, sertraline exposure was associated with an increased risk of atrial/ventricular defects specifically (risk ratio [RR], 1.34; 95% CI, 1.02-1.76; 9 exposed cases), and craniosynostosis (RR, 2.03; 95% CI, 1.09-3.75; 3 exposed cases). Exposure to SSRIs other than sertraline during the first trimester of pregnancy was associated with craniosynostosis (RR, 2.43; 95% CI, 1.44-4.11; 19 exposed cases), and musculoskeletal defects (RR, 1.28; 95% CI, 1.03-1.58; 104 exposed cases). CONCLUSION: Sertraline use during the first trimester of pregnancy was associated with an increased risk of atrial/ventricular defects and craniosynostosis above and beyond the effect of maternal depression. Nonsertraline SSRIs were associated with an increased risk of craniosynostosis and musculoskeletal defects.

High-risk single ventricle palliation in children with Down syndrome: single institution experience.

BACKGROUND: Of the children with Down syndrome 40-50% have cardiac defects and the majority of these cardiac defects are amenable to biventricular repair. The outcome of single ventricle palliation is improving; nonetheless, there are limited data on Down syndrome patients with associated high-risk factors undergoing single ventricle palliation. Our aim was to study the outcomes of children with Down syndrome and high-risk factors on the single ventricle palliation pathway. METHODS: A retrospective study on all patients with Down syndrome on the single ventricle palliation pathway from 2005 until 2011 was conducted. Operative, clinical, echocardiographic, haemodynamic data, and follow-up data were reviewed. RESULTS: A total of 310 patients underwent at least one single ventricle surgical intervention. Of those, eight patients had Down syndrome, five of which had associated risk factors - low birth weight, high pulmonary vascular resistance, pulmonary vein stenosis, significant atrioventricular valve regurgitation, and extracardiac anomalies. Mortality in the high-risk group was 80% (4/5), compared with 33% (1/3) in the non-high-risk patients. Overall, after a median follow-up period of 138 days (8-576 days), only 37.5% (3/8) of patients were alive. CONCLUSION: Despite many improvements in the care of single ventricle patients, the fate of those with Down syndrome and associated high-risk factors remains poor. Further multicentre longer-term studies are needed to validate and quantify the cumulative effects of negative prognostic factors in this complex group of patients.

Fetal phenotype associated with the 22q11 deletion.

The 22q11 deletion syndrome is one of the most common human microdeletion syndromes, with a wide spectrum of abnormalities. The fetal phenotype associated with the 22q11 deletion is poorly described in the literature. A national retrospective study was performed from 74 feto-pathological examinations. The objectives were to evaluate the circumstances of the 22q11 deletion diagnosis and to describe fetal anomalies. Post mortem examinations were performed after 66 terminations of pregnancy and eight fetal deaths. The series included nine fetuses from the first trimester, 55 from the second trimester, and ten from the third trimester. A 22q11 FISH analysis was recommended for 57 fetuses after multidisciplinary prenatal diagnostic counseling and for 17 fetuses by a fetal pathologist. Conotruncal heart defects were the most common anomalies (65 fetuses), followed by thymus defects (62 fetuses), and malformations of the urinary tract (25 fetuses). This study identified several unusual and severe features rarely described in the literature. Neurological abnormalities were described in ten fetuses, with seven neural tube defects and five arhinencephalies. This series also included lethal malformations: two hypoplastic left heart syndromes, two bilateral renal agenesis, and one tracheal agenesis. Genetic analysis for a 22q11 deletion is usually indicated when a congenital conotruncal heart and/or thymus defect is detected, but might also be useful in case of other lethal or severe malformations that initially led to the termination of pregnancy.

Accessory tricuspid valve leaflet and an anomalous muscle bundle in the right ventricular outflow tract in a patient with double-outlet right ventricle: a rare case report.

Double-outlet right ventricle (DORV), a clinically important congenital heart disease, occurs in 1-3% of persons with congenital heart disease. It may occur as an isolated cardiac defect, together with other cardiac lesions, or in association with extracardiac anomalies. Other rare cardiac anomalies include an anomalous muscle bundle (AMB) in the right ventricular outflow tract (RVOT) and an accessory tricuspid valve leaflet. We report a very rare case of concomitant DORV, AMB in the RVOT and accessory tricuspid valve leaflet in a 17-year-old male patient. The patient eventually died from severe decompensated heart failure. To the best of our knowledge, such a case has not been previously reported in the literature.

The anatomy of nuchal translucency at 10-14 weeks gestation in fetuses with trisomy 21: An incredible medical mystery.

Nuchal translucency (NT) is a hypo-echoic region of subcutaneous fluid accumulation in the posterior neck at the level of the cervical spine between the skin and soft tissues found at 10-14 weeks gestation. This ultrasound finding is important because increased NT measurements place the fetus at increased risk for chromosomal and structural abnormalities. It is a fascinating phenomenon that displays the intersection of anatomy, development, and imaging. In addition, with the ever increasing use of ultrasound in anatomy, NT is a readily demonstrable example of how important ultrasound has become to the practice of medicine. Articles on NT were obtained from OVID database and reviewed for their contribution to an understanding of the anatomical basis of NT. Whereas it is well established that the ultrasound finding of increased NT is a sensitive marker for Trisomy 21 at 10-14 weeks gestation, why this phenomena occurs has yet to be explained. The basis of nuchal edema is most likely multifactorial, a combination of delayed or disturbed lymphangiogenesis, cardiac and vascular abnormalities, and abnormal extracellular matrix components. Further research on the development of the fetal head and neck related to lymphatic development and fluid regulation during 8-14 weeks gestation will enable a greater understanding of how and why increased NT occurs compared to what is currently known. This could lead to early intervention to manage some of the repercussions of Trisomy 21 and other abnormalities related to NT.

Resveratrol ameliorates cyprodinil-induced zebrafish cardiac developmental defects as an aryl hydrocarbon receptor antagonist.

Cyprodinil, a globally utilized broad-spectrum pyrimidine amine fungicide, has been observed to elicit cardiac abnormality. Resveratrol (RSV), a naturally occurring polyphenolic compound, showcases remarkable defensive properties in nurturing cardiac development. To investigate whether RSV could protect against cyprodinil-induced cardiac defects, we exposed zebrafish embryos to cyprodinil (500 µg/L) in the presence or absence of RSV (1 µM). Our results showed that RSV significantly mitigated the decrease of survival rate and embryo movement and the hatching delay induced by cyprodinil. In addition, RSV also improved cyprodinil-induced zebrafish cardiac developmental toxicity, including pericardial edema and cardiac function impairment. In mechanism, RSV attenuated the cyprodinil-induced changes in mRNA expression involved in cardiac development, such as myh6, myl7, tbx5, and gata4, and calcium ion channels, such as ncx1h, slc8a4a, and atp2a2b. We further showed that RSV might inhibit the activity of aryl hydrocarbon receptor (AhR) signaling pathways induced by cyprodinil. In summary, our findings establish that the protective effects of RSV against the cardiac developmental toxicity are induced by cyprodinil due to its remarkable ability to inhibit AhR activity. Our findings not only shed light on a new avenue for regulating and ensuring the safe utilization of cyprodinil but also presents a novel concept to promote its responsible use.