Rate Of Chromosomal Aberrations Research Articles

Evaluation of genotoxicity and teratogenicity of phillyrin

Phillyrin is extracted from Forsythia suspensa (Thunb.) Vahl, is significantly higher in (unripe Forsythiae Fructus) Qing qiao than in (ripe Forsythiae Fructus) Lao qiao fruits of the plant. However, the toxicity of phillyrin has not been adequately investigated. The study investigates the genetic and teratogenic effects of phillyrin to determine its safety profile. Assessing the genotoxicity and teratogenicity of phillyrin involved various tests, such as the bacterial reverse mutation assay, mammalian erythrocyte micronucleus assay, spermatocyte chromosome aberration assay, and teratogenicity assay. The results demonstrated that phillyrin exhibited no discernible impact on the following: number of colonies that spontaneously revert for Salmonella typhimurium TA 97, TA98, TA100, TA102, and TA1535, frequency of bone marrow polychromatic erythrocytes, and the rate of chromosomal aberrations. In the teratogenicity test, the pregnant rats exhibited no signs of toxicity or abnormal changes, and the growth, embryonic development, and visual anatomy of each pup were normal. In comparison with the negative control group, there were no significant differences in fetal body weight, mortality, deformity rate, malformed nest rate, gravid uterus weight, average number of fetuses per litter, fetal body length, or visceral and skeletal development in each dose group. In conclusion, these findings provide evidence that phillyrin does not exhibit genotoxic or teratogenic effects, supporting its potential safety for pharmacological applications.

Evaluation of XQ528 tartrate on embryo-fetus developmental toxicity in SD rats and genotoxicity

The effects of XQ528 tartrate on the embryonic and fetal development of fertile Sprague-Dawley (SD) rats, along with their embryos and littermates, were evaluated using an embryo-fetus developmental toxicity assay. fertile SD rats exhibited no significant general toxic effects when administered doses of 0.25, 1.25, and 5.0 mg/kg intranasally from days 6 to 15 of gestation. The genotoxicity of the compound was evaluated through an amalgam of tests that included the Ames test, the Chinese hamster ovary (CHO) cell chromosome aberration test, and the micronucleus test in ICR mice. The results from the Ames test indicated non-mutagenicity at concentrations of 5000, 500, 50.0, 5.0, and 0.5 μg/dish across strains TA97, TA98, TA100, TA102, and TA1535. Additionally, the chromosomal aberration rates in CHO cells were not significantly altered at concentrations of 50.5, 101.0, and 202.0 μg/mL. No micronuclei induction was observed in ICR mice at dosage levels of 11.25, 22.50, and 45.00 mg/kg post intranasal administration. In conclusion, the no observed adverse effect level (NOAEL) for developmental toxicity of XQ528 tartrate in fertile SD rats, embryos, and littermates under the test conditions in this study was established at 5.0 mg/kg/day. Under these test conditions, XQ528 tartrate did not exhibit any significant genotoxic or carcinogenic potential.

Occupational health risk recognition, evaluation, and management of radiation workers in Gansu province, China

ObjectiveIn order to protect the health of radiation workers, scientific management of radiation workplace protection is implemented, and occupational health risks of radiation workplaces in Gansu Province, China are identified and evaluated through monitoring. MethodsThe basic situation of occupational health management of radiological workers in 1366 radiological diagnosis and treatment institutions was investigated, and 596 monitoring hospitals were selected for occupational health monitoring. Using a 2-IN∗2-in NaI (Tl) scintillation spectrometer and its supporting software, internal thyroid irradiation monitoring was performed. Fifty-one underground workers in a deep mine iron mine were selected to monitor the effect of high radon exposure. Results11 (6%) monitored hospital interventional radiology staff detected lead outside the aprons between 5 mSv and 20 mSv during a single monitoring period; In nuclear medicine, radiation monitoring in the thyroid detected 3(15%) people with doses between 5 mSv and 20msv.The chromosome aberration rate and Detection rate of posterior pole subcapsular opacification of interventional radiation group and nuclear medicine group was higher than that of conventional radiation group, and the difference between interventional radiation group and conventional medicine group was statistically significant. Abnormal detection of tumor markers in serum after sustained radon exposure accounted for 39.2% of NSE(neuron-specific enolase), 22.5% of SCC(squamous cell carcinoma associated antigen), and 5.9% of CyFRA21-1(cytokeratin 19 fragment), respectively, chest low-dose CT showed plaque and stripe shadow in 21 cases (41.2%) and nodules in 16 cases (31.4%). ConclusionIndividual dose monitoring found that radiation workers engaged in interventional radiology were exposed to higher doses and had higher occupational risks. The results of occupational health examination show that there is a certain degree of radiation injury in interventional radiology and nuclear medicine workers. Nuclear medicine radiation monitoring results show that some workplaces have radioactive contamination. The radon exposure of deep mine miners has a higher occupational risk of lung cancer caused by high radon.The analysis of chromosome aberration is an important index of occupational health monitoring of radiation workers.

Clinical Analysis of Y Chromosome Microdeletions and Chromosomal Aberrations in 1596 Male Infertility Patients of the Zhuang Ethnic Group in Guangxi.

The long arm of the Y chromosome (Yq) contains many amplified and palindromic sequences that are prone to self-reorganization during spermatogenesis, and tiny submicroscopic segmental deletions in the proximal Yq are called Y chromosome microdeletions (YCM). A retrospective study was conducted on male infertility patients of Zhuang ethnicity who presented at Reproductive Medical Center of Nanningbetween January 2015 and May 2023. Seminal fluid was collected for standard examination. YCM were detected by using a combination of multiplex PCR and agarose gel electrophoresis. Preparation of peripheral blood chromosomes and karyotyping of chromosomes was performed. 147 cases (9.22%) of YCM were detected in 1596 maleinfertility patients of Zhuang ethnicity. Significant difference was found in the detection rate of YCM between the azoospermia group and the oligospermia group (P < 0.001). Of all types of YCM, the highest detection rate was AZFc (n = 83), followed by AZFb + c (n = 28). 264 cases (16.54%) of sex chromosomal aberrations were detected. The most prevalent karyotype was 47, XXY (n = 202). The detection rate of sex chromosomal aberrations in azoospermia group was higher than that in severe oligospermia group and oligospermia group, and the differences were significant (P < 0.001). 28 cases (1.57%) of autosomal aberrations and 105 cases (6.58%) of chromosomal polymorphism were identified. The current research has some limitations due to the lack of normal men as the control group but suggests that YCM and chromosomal aberrations represent key genetic factors influencing spermatogenesis in infertile males of Zhuang ethnicity in Guangxi.

Chromosomal aberration analysis: Novel noninvasive techniques for early-stage cancer screening

ObjectiveChromosome breakage is a catastrophic event that leads to the progressive development and progression of cancer. In order to analyze the changes of peripheral blood microenvironment of tumor patients, to explore the indicators of non-specific non-invasive tumor early screening. This paper presents a new idea of whether the gene sequence near the DNA damage break point is the gene sequence that controls the unrestricted growth of normal cells. MethodsThe chromosomal aberrations of peripheral blood lymphocytes were analysed in 60 healthy adult and 49 cancer patients before radiotherapy. ResultsThe detection rate of chromosomal aberrations was high in tumor patients, and “dicentric + translocations” of chromosomes were detected in 36 patients (73.47 %). The chi-square test showed statistically significant differences (P < 0.01), and chromosome adhesion and dissolution were observed. Conclusions“Dicentric + Translocation” chromosome can be used as a nonspecific early screening indicator for cancer. This is worthy of further study. This index can be used to determine the genetic basis of various cancers at the gene level to modify the base sequence and prevent the occurrence of cancer. It is worthy of further study, and it can provide a new method for gene therapy of tumors.

Genotoxicity Associated with Retroviral CAR Transduction of ATM-Deficient T Cells.

Somatic variants in DNA damage response genes such as ATM are widespread in hematologic malignancies. ATM protein is essential for double-strand DNA break repair. Germline ATM deficiencies underlie ataxia-telangiectasia (A-T), a disease manifested by radiosensitivity, immunodeficiency, and predisposition to lymphoid malignancies. Patients with A-T diagnosed with malignancies have poor tolerance to chemotherapy or radiation. In this study, we investigated chimeric antigen receptor (CAR) T cells using primary T cells from patients with A-T (ATM-/-), heterozygote donors (ATM+/-), and healthy donors. ATM-/- T cells proliferate and can be successfully transduced with CARs, though functional impairment of ATM-/- CAR T-cells was observed. Retroviral transduction of the CAR in ATM-/- T cells resulted in high rates of chromosomal lesions at CAR insertion sites, as confirmed by next-generation long-read sequencing. This work suggests that ATM is essential to preserve genome integrity of CAR T-cells during retroviral manufacturing, and its lack poses a risk of chromosomal translocations and potential leukemogenicity. Significance: CAR T-cells are clinically approved genetically modified cells, but the control of genome integrity remains largely uncharacterized. This study demonstrates that ATM deficiency marginally impairs CAR T-cell function and results in high rates of chromosomal aberrations after retroviral transduction, which may be of concern in patients with DNA repair deficiencies.

Constitutional chromosomal anomalies in children, fetal alcohol syndrome, and maternal toxicant exposures: A longitudinal cohort study

DNA alterations in gametes, which may occur either spontaneously or as a result of exposure to genotoxicants, can lead to constitutional chromosomal anomalies in the offspring. Alcohol is an established genotoxicant. The goal of this hypothesis-testing longitudinal cohort study was to evaluate the effect of significant/sustained maternal alcohol exposure on clinically diagnosed constitutional chromosomal anomalies among children diagnosed with fetal alcohol syndrome (FAS). De-identified eligibility and claim healthcare records, prospectively generated from the 1990–2012 Florida Medicaid system within the Independent Healthcare Research Database (IHRD), were analyzed. Children examined were continuously eligible with ≥ 8 outpatient office visits during the 96-month period following birth. Among these children, 377 were diagnosed with FAS and 137,135 were not. The incidence rate of chromosomal anomalies involving segregation (trisomy 13, 18, or 21, n = 625), microdeletions (microdeletion syndromes, n = 39), and point mutations (sickle-cell anemia/cystic fibrosis, n = 2570) were examined using frequency risk ratio (RR) and logistic regression (adjusted odds ratio (aOR) for sex, race, residence, socioeconomic/environmental exposure status, and birth date) models. The incidence rates of chromosomal anomalies involving segregation (RR=5.92, aOR=5.85) and microdeletions (RR=41.6, aOR=34.1) were significantly increased in the FAS cohort as compared to the non-diagnosed cohort, but there was no difference in the incidence rate of point mutations (RR=1.14, aOR=1.29). Maternal toxicant exposure should be considered in the etiology of constitutional chromosomal anomaly in offspring.

Contribution of radioactive particles to the post-explosion exposure of atomic bomb survivors implied from their stable chromosome aberration rates.

Even today when nearly 80 years have passed after the atomic bomb (A-bomb) was dropped, there are still debates about the exact doses received by the A-bomb survivors. While initial airborne kerma radiation (or energy spectrum of emitted radiation) can be measured with sufficient accuracy to assess the radiation dose to A-bomb survivors, it is not easy to accurately assess the neutron dose including appropriate weighting of neutron absorbed dose. Particularly, possible post-explosion exposure due to the radioactive particles generated through neutron activation have been almost neglected so far, mainly because of a large uncertainty associated to the behavior of those particles. However, it has been supposed that contribution of such non-initial radiation exposure from the neutron-induced radioactive particles could be significant, according to the findings that the stable chromosomal aberration rates which indicate average whole-body radiation doses were found to be more than 30% higher for those exposed indoors than for those outdoors even at the same initial dose estimated for the Life Span Study. In this Mini Review article, the authors explain that such apparently controversial observations can be reasonably explained by assuming a higher production rate of neutron-induced radioactive particles in the indoor environment near the hypocenter.

Clinical value of screening prenatal ultrasound combined with chromosomal microarrays in prenatal diagnosis of chromosomal abnormalities

Objective To evaluate the clinical value of ultrasound findings in the screening of fetal chromosomal abnormalities and the analysis of risk factors for chromosome microarray analysis (CMA) abnormalities. Methods We retrospectively analyzed the datasets of 15,899 pregnant women who underwent prenatal evaluations at Affiliated Maternity and Child Health Care Hospital of Nantong University between August 2018 and December 2022. Everyone underwent ultrasound screening, and those with abnormal findings underwent CMA to identify chromosomal abnormalities. Results The detection rates for isolated ultrasound anomalies and combined ultrasound and CMA anomalies were 11.81% (1877/15,899) and 2.40% (381/15,899), respectively. Among all ultrasound abnormalities, detection rates for isolated ultrasound soft marker anomalies, isolated structural abnormalities, and both ultrasound soft marker anomalies with structural abnormalities were 82.91% (1872/2258), 15.99% (361/2258), and 1.11% (25/2258), respectively. The detection rate of abnormal chromosomes in pregnant women with abnormal ultrasound results was 16.87% (381/2258). The detection rates were 13.33% in cases with two or more ultrasound soft markers anomalies, 47.37% for two or more structural anomalies, and 48.00% for concomitant ultrasound soft marker and structural anomalies. Conclusions Enhanced detection rates of chromosomal anomalies in fetal malformations are achieved with specific ultrasound findings (NT thickening, cardiovascular abnormalities, and multiple soft markers) or when combined with high-risk factors (advanced maternal age, familial history, parental chromosomal anomalies, etc.). When the maternal age is over 35 and with ≥2 ultrasound soft marker anomalies accompanied with any high-risk factors, CMA testing can aid in the diagnosis of prenatal chromosomal abnormalities.

Analysis of the results of occupational health examination of radiation workers in Shaanxi Province

Objective: To analyze the results of occupational health examinations of radiation workers in Shaanxi Province, and to provide basis and reference for effectively conduct occupational health monitoring. Methods: From April 2016 to January 2022, a questionnaire survey was conducted to collect the basic information on occupational health examinations of qualified radiation workers in Shaanxi Province from 2016 to 2021. Based on the abnormal rate of occupational health among radiation workers, 1018 people were randomly selected using a cluster stratified sampling method to analyze the occupational health examination results of different positions, types of work, gender, length of service, and exposure doses. Results: The chromosomal aberration rates of peripheral blood lymphocytes among radiation workers in Shaanxi Province from 2016 to 2021 were 0.26% (10/3876), 0.77% (27/3512), 0.16% (16/10153), 0.09% (13/14769), 0.10% (13/13399), and 0.12% (20/16671), respectively. The abnormal rates of thyroid ultrasound examination were 32.33% (150/464), 24.46% (649/2653), 55.24% (786/1423), 32.89% (888/2700), 35.69% (1475/4133), and 42.51% (1993/4688), respectively. There was a statistically significant difference in the abnormal rates among different years (P<0.05). The abnormal rate of renal function examination in male radiation workers was higher than that in females (P<0.05). Compared with non medical users, the abnormal rates of renal function, thyroid function, and blood routine examination in medical radiation workers were higher (P<0.05), and the abnormal rates of renal function, thyroid function, and blood routine examination in medical applications were higher than those in radiation diagnosis, nuclear medicine, and radiation therapy (P<0.05). The abnormal rates of electrocardiogram, chest X-ray, blood pressure, thyroid function, and blood routine increased with the length of service (P<0.05). The abnormal rates of blood pressure, liver function, kidney function, thyroid function, and blood routine examination increased with the exposure dose (P<0.05) . Conclusion: The occupational health status of radiation workers is not optimistic. Occupational health monitoring should be strengthened, especially interventional radiation diagnosis occupational health examination, as well as changes in the indicators of sensitive organs such as eye lens and thyroid, so as to ensure the health of radiation workers.

Evaluation of chromosomal abnormalities in the postnatal cohort: A single-center study on 14,242 patients.

Chromosomal analysis is a laboratory technique used to examine the chromosomes of an individual, offering insights into chromosome numbers, structures, and arrangements to diagnose and comprehend genetic diseases. This retrospective study provides a comprehensive understanding of the distribution by indications in a large cohort of 14,242 patients and the frequency of chromosomal abnormalities in different clinical populations. The study examined various indications for karyotype evaluation, with recurrent pregnancy loss being the most common indication, followed by intellectual disability, dysmorphic features, congenital anomalies, and developmental delay. The overall chromosomal abnormality rate was found to be 5.4%, with numerical abnormalities accounting for the majority of cases (61.7%). Trisomies, particularly trisomy 21, were the most frequent numerical abnormalities. In terms of structural abnormalities, inversions and translocations were the most commonly identified. The rates of chromosomal anomalies varied in specific indications such as amenorrhea, disorders of sex development, and Turner syndrome. The study also highlighted significant differences between males and females in the presence of chromosomal abnormalities across certain indications. Males exhibited a higher incidence of chromosomal abnormalities in cases of Down syndrome and infertility, whereas females showed higher abnormalities in terms of recurrent pregnancy loss. While this study provides valuable insights into the frequency and distribution of chromosomal abnormalities, it has limitations, including its retrospective design and reliance on data from a single medical genetics department. Nevertheless, the findings emphasize the importance of karyotype analysis in diagnosing chromosomal disorders and providing appropriate management, while also pointing to potential gender-related variations in chromosomal abnormalities that warrant further investigation.

Analysis of chromosome aberrations in peripheral blood lymphocyte of medical radiation workers in a tertiary hospital

Objective: To analyze the level of chromosome aberration in lymphocytes of medical radiation workers and its influencing factors. Methods: From July to September 2020, 252 medical workers in a tertiary hospital were selected as the study subjects and 107 preserviceworkers were selected as the control group. The Chromosomal aberrations of peripheral blood lymphocytes were measured using conventional cytogenetic analysis method, and the differences were analyzed. Results: The frequencies of dicentric puls centric ring, total chromosome-type aberrations, and abnormal detection rate in the radiation group were significantly higher than those in the control group (Z=2.59, 3.74, 9.99, P<0.05). There was significant difference in the frequencies of dicentric plus centric ring and total chromosome-type aberrations among different types of work (χ(2)=8.59, 8.17, 11.39, P<0.05), and the frequencies of dicentric plus centric ring were significantly higher in the interventional radiology group than those in diagnostic radiology (χ(2)=2.90, P<0.05), While the rates of acentric fragment and total chromosome-type aberrations were significantly higher in the nuclear medicine group than those in diagnostic radiology (χ(2)=2.81, 3.19, P<0.05). The difference in the abnormal detection rate of chromosome aberrations between different types of work was statistically significant (P<0.05), and the rate in the interventional radiology group was significantly higher than that in the diagnostic radiology group (χ(2)=7.66, P<0.05). There was no significant difference in chromosome aberration level and abnormal detection rate among different working ages (P>0.05). Poisson regression analysis indicated that the type of work is a risk factor for chromosomal aberration [IRR=2.31 (nuclear medicine group), 1.66 (Radiation therapy), and 1.78 (interventional group) ; P<0.05]. Conclusion: Ionizing radiation causes certain radiation damage to medical radiology workers, and the frequencies of chromosome aberration in the radiation workers of nuclear medicine and interventional radiology groups are relatively high, so radiation protection should be strengthened to ensure the health of relevant workers.

Fetal congenital gastrointestinal obstruction: prenatal diagnosis of chromosome microarray analysis and pregnancy outcomes

ObjectiveThe aim of this study was to investigate the incidence of chromosome anomalies in different types of congenital gastrointestinal obstruction and assess pregnancy outcomes of fetuses with congenital gastrointestinal obstruction.MethodsA total of 64 cases with gastrointestinal obstruction between January 2014 and December 2020 were enrolled in this study. They were divided into three groups according to sonographic images. Group A: isolated upper gastrointestinal obstruction; Group B: isolated lower gastrointestinal obstruction; Group C: non-isolated gastrointestinal obstruction. The rate of chromosome anomalies in different groups was calculated. Pregnant women with amniocentesis were followed up by medical records and telephone. The follow-up included pregnancy outcomes and development of the live born infants.ResultFrom January 2014 to December 2020, there were 64 fetus with congenital gastrointestinal obstruction underwent chromosome microarray analysis(CMA), the overall detection rate of CMA testing was 14.1%(9/64). The detection rate of Group A, B and C were 16.2%, 0 and 25.0% respectively. 9 fetuses with abnormal CMA results were all terminated. Among 55 fetuses with normal chromosomes, 10(18.2%) fetuses were not found to have any gastrointestinal obstruction after birth. 17(30.9%) fetuses were diagnosed with gastrointestinal obstruction and underwent surgical treatment after birth, one of which had lower gastrointestinal obstruction combined with biliary obstruction and died due to liver cirrhosis. 11(20.0%) pregnancy were terminated due to multiple abnormalities. 5(9.1%) fetuses were intrauterine death. 3(5.5%) fetuses were neonatal deaths. 9(16.4%) fetuses were lost to follow-up.ConclusionIt is crucial to understand whether the gastrointestinal tract abnormality is isolated or associated to other findings. The risk of chromosomal abnormalities in fetuses with isolated lower gastrointestinal obstruction is lower than upper gastrointestinal obstruction. While genetic abnormalities excluded, a promising prognosis is expected for fetuses with congenital gastrointestinal obstruction.

Association between low fetal fraction in cell-free DNA screening and fetal chromosomal aberrations: A systematic review and meta-analysis.

To perform a systematic review and meta-analysis of the available literature on low fetal fraction (LFF) in cell-free DNA (cfDNA) screening and the risk of fetal chromosomal aberrations. We searched articles published between January 2010 and May 2021 in PubMed and EMBASE databases. Risk of bias was assessed using QUADAS-2. Twenty-seven studies met the inclusion criteria, comprising data of 243,700 singleton pregnancies. Compared to normal fetal fraction, LFF was associated with a higher risk of trisomy 13 (OR 5.99 [3.61-9.95], I 2 of heterogeneity = 0%, n=22 studies), trisomy 18 (OR 4.46 [3.07-6.47], I2 = 0%, n=22 studies), monosomy X (OR 5.88 [2.34-14.78], I2 = 18%, n=10 studies), and triploidy (OR 36.39 [9.83-134.68], I2 = 61%, n=6 studies), but not trisomy 21 (OR 1.25 [0.76-2.03], I2 = 36%, n=23 studies). LFF was also associated with a higher risk of various other types of fetal chromosomal aberrations (OR 4.00 [1.78-9.00], I2 = 2%, n=11 studies). Meta-analysis of proportions showed that absolute rates of fetal chromosomal aberrations ranged between 1-2% in women with LFF. A limitation of this review is the potential risk of ascertainment bias because of differences in outcome assessment between pregnancies with LFF and those with normal fetal fraction. Heterogeneity in population characteristics or applied technologies across included studies may not have been fully addressed. An LFF test result in cfDNA screening is associated with an increased risk of fetal trisomy 13, trisomy 18, monosomy X, and triploidy, but not trisomy 21. Further research is needed to assess the association between LFF and specific other types of fetal chromosomal aberrations. This article is protected by copyright. All rights reserved.

Incidence and Types of Fetal Chromosomal Abnormalities in First Trimester of Thai Pregnant Women between Miscarriages and Intrauterine Survivals

Abortion is a common pregnancy complication. Fetuses with several types of chromosomal abnormalities are aborted during the first trimester, while others have a better chance of surviving. This research aims to study and compare the incidence and types of fetal chromosomal abnormalities during the first trimester of Thai pregnant women between miscarriages and intrauterine survivals. Cytogenetic and BACs-on-Beads™ assays were assessed from 2010 to 2020 in Ramathibodi Hospital using first trimester samples of 265 chorionic villi as a retrospective study. Chromosomal abnormalities were observed in 135 cases (50.94%) including 38.11% miscarriages and 12.83% intrauterine survivals. In total, 75.56% single autosomal trisomies, 18.52% sex chromosome aneuploidies, 5.19% double aneuploidies, and 0.74% structural abnormalities were detected. In miscarriages, all chromosomes were involved in abnormalities except chromosomes 1, 5, 8, 9, 11, and 17, while survivals had only trisomy 13, 18, 21, and sex chromosome aneuploidy. Trisomy 16 and 18 were the most common abnormalities in miscarriages and intrauterine survivals, respectively. The highest rate of chromosomal aberrations was demonstrated in 8–9⁺⁶ and 12–13⁺⁶ weeks of gestation in miscarriages and intrauterine survivals, respectively. Correlation between chromosomal abnormalities and maternal age <35 years and ≥35 years was significant (p < 0.05) in intrauterine survival and first trimester groups.

Acute toxicity and genotoxicity studies on new melatonergic antidepressant GW117

GW117, a novel derivate compound of agomelatine that acts as both a 5-HT2C receptor antagonist and a MT1/MT2 receptor agonist, likely underlines the potent antidepressant action with less hepatotoxicity than agomelatine. We evaluated the acute toxicity of GW117, and the genotoxicity of GW117 using bacterial reverse mutation test, mammalian chromosomal aberration test in Chinese hamster lung cells (CHL) and mouse bone marrow micronucleus test. The acute toxicity test results showed that maximum tolerated dose (MTD) of GW117 was 2000 mg/kg, under which mean Cmax and AUC0→t was 10,782 ng/mL and 81,046 ng/mL × h, respectively. The result of bacterial reverse mutation test showed that the number of bacterial colonies in each dose group of GW117 did not increase significantly compared with that in the solvent control group with or without S9 metabolic activation system. In vitro chromosome aberration test of CHL cells, the chromosome aberration rate of each dose group of GW117 did not increase with or without S9 metabolic activation system. In mouse micronucleus test, the highest dose was 2000 mg/kg, the micronucleus rate did not increase significantly. Under the conditions of this study, the MTD of a single GW117 administration was 2000 mg/kg, there was no genotoxicity effect of GW117.

The association between a carrier state of FMR1 premutation and numeric sex chromosome variations.

Women carriers of FMR1 premutation are at increased risk of early ovarian dysfunction and even premature ovarian insufficiency. The aim of this study was to examine a possible association between FMR1 permutation and numeric sex chromosome variations. A retrospective case-control study conducted in the reproductive center of a university-affiliated medical center. The primary outcome measure was the rate of sex chromosomal numerical aberrations, as demonstrated by haplotype analyses, in FMR1 premutation carriers compared to X-linked preimplantation genetic testing for monogenic/single gene defect (PGT-M) cycles for other indications that do not affect the ovarian follicles and oocytes. A total of 2790 embryos with a final genetic analysis from 577 IVF PGT-M cycles were included in the final analysis. Mean age was similar between the groups, however, FMR1 carriers required more gonadotropins, and more women were poor responders with three or less oocytes collected. The ratio of embryos carrying a numeric sex chromosome variation was similar: 8.3% (138/1668) of embryos in the FMR1 group compared to 7.1% (80/1122) in the controls. A subgroup analysis based on age and response to stimulation has not demonstrated a significant difference either. Although carriers of FMR1 premutation exhibit signs of reduced ovarian response, it does not seem to affect the rate of numeric sex chromosomal variation compared to women undergoing PGT-M for other indications. This suggests that the mechanism for chromosomal number aberrations in women at advanced maternal age are different to those FMR1 premutation carriers with poor ovarian reserve.

Screening of in vitro-produced cattle embryos to assess incidence and characteristics of unbalanced chromosomal aberrations

In cattle, pregnancy rates of in vitro-produced embryos are lower than those of in vivo-produced embryos. One of the reasons may be the increase in chromosomal aberrations due to in vitro maturation and fertilization of the oocyte. Currently, embryo transfer is commonly applied in nucleus cattle breeding programs, and the embryos are genotyped for genomic selection. Therefore, intensity data from SNP arrays can be exploited for preimplantation genetic testing by screening the intensity data of the embryos for unbalanced chromosomal aberrations. A total of 558 stage 8 Dutch Holstein embryos genotyped with SNP arrays were screened in an observational study in retrospect. We found a 5% incidence rate of unbalanced chromosomal aberrations (aneuploidy and ploidy issues) among 430 successfully genotyped cattle embryos. The 22 affected embryos showed either aneuploidy or ploidy issues; monosomy was most frequently observed (14/22). In most cases (16/19) the maternal chromosome or chromosomes were lost or gained. One of the monosomy cases gave rise to a live-born fully diploid individual, suggesting mosaicism. Given that embryo genotypes are readily available, monitoring incidence can easily be applied. Moreover, selection for euploid embryos may improve pregnancy rates for in vitro embryo transfer.

THE LANDSCAPE OF CHROMOSOMAL ABERRATIONS IN 10,000 EMBRYOS DERIVED FROM FRESH DONOR OOCYTES

Information on chromosomal aberration rates in embryos derived from a young population, such as egg donors, is limited. PGT-A is the best predictive tool for embryo selection. It is most often offered to patients with advanced age, but with contradicting recommendations in younger patients. The objective was to evaluate the type and frequency of chromosomal aberrations in embryos derived from fresh young donor oocytes detected at NGS resolution of 10Mb and >30% mosaicism.

Chromosomal Aberrations in Large Japanese Field Mice (Apodemus speciosus) Captured in Various Periods after Fukushima Daiichi Nuclear Power Plant Accident.

After the Fukushima Daiichi Nuclear Power Plant accident, we studied the chromosomal aberrations (dicentrics and translocations) in the splenic lymphocytes of wild mice inhabiting Fukushima prefecture. Here, we report the frequencies of chromosomal aberrations in large Japanese field mice (Apodemus speciosus) captured from 2012 to 2016 in a heavily contaminated area. The chromosomal aberrations were detected using newly developed 4-color FISH (fluorescence in situ hybridization) with A. speciosus chromosome 1-, 3-, 4- and 5-specific painting probes. The frequencies of chromosomal aberrations in mice captured in July 2012 and October 2014 were significantly higher than that in the mice inhabiting the non-contaminated control area; however, the frequency of chromosomal aberrations in mice captured in January 2016 was not. The frequency of chromosomal aberrations in individual mice tended to increase with certain dose rates and accumulated doses. Regression tree analyses suggested increasing chromosomal aberration rate in mice exposed to chronic radiation at dose rates of more than 1.1 mGy day-1 and at accumulated doses of more than 200 mGy. It is concluded that ambient dose rates in the most severely contaminated area of Fukushima prefecture and radiation doses to wild mice inhabiting this area decrease with time; consequently, chromosomal aberrations induced by radiation have not been detected 5 years after the accident.