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prenatal amoxicillin exposure induces developmental toxicity in fetal mice and its characteristics

Journal of Environmental Sciences 2024年第3期137卷 287-301页

作者： Yongguo Dai Yu Peng Wen Hu Yi Liu Hui Wang Department of Pharmacology Wuhan University School of Basic Medical SciencesWuhan 430071China Department of Pharmacy Zhongnan Hospital of Wuhan UniversityWuhan 430071China Hubei Provincial Key Laboratory of Developmentally Originated Disease Wuhan 430071China

Amoxicillin,a widely used antibiotic in human and veterinary pharmaceuticals,is now considered as an“emerging contaminant”because it exists widespreadly in the environment and brings a series of adverse outcomes.Currently,systematic studies about the developmental toxicity of amoxicillin are still lacking.We explored the potential effects of amoxicillin exposure on pregnancy outcomes,maternal/fetal serum phenotypes,and fetal multiple organ development in mice,at different doses(75,150,300 mg/(kg·day))during late-pregnancy,or at a dose of 300 mg/(kg·day)during different stages(mid-/latepregnancy)and courses(single-/multi-course).Results showed that prenatal amoxicillin exposure(PAmE)had no significant infuence on the body weights of dams,but it could inhibit the physical development and reduce the survival rate of fetuses,especially during the midpregnancy.Meanwhile,PAmE altered multiple maternal/fetal serum phenotypes,especially in fetuses.Fetal multi-organ function results showed that PAmE inhibited testicular/adrenal steroid synthesis,long bone/cartilage and hippocampal development,and enhanced ovarian steroid synthesis and hepatic glycogenesis/lipogenesis,and the order of severity might be gonad(testis,ovary)>liver>others.Further analysis found that PAmE-induced multiorgan developmental and functional alterations had differences in stages,courses and fetal gender,and the most obvious changes might be in high-dose,late-pregnancy and multicourse,but there was no typical rule of a dose-response relationship.In conclusion,this study confirmed that PAmE could cause abnormal development and multi-organ function alterations,which deepens our understanding of the risk of PAmE and provides an experimental basis for further exploration of the long-term harm.

关键词： Amoxicillin prenatal exposure Fetal development Organ function Developmental toxicity

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prenatal metal mixture exposure and birth weight: A two-stage analysis in two prospective cohort studies

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Eco-Environment & Health 2022年第3期1卷 165-171页

作者： Jie Hu George D.Papandonatos Tongzhang Zheng Joseph M.Braun Bin Zhang Wenyu Liu Chuansha Wu Aifen Zhou Simin Liu Stephen L.Buka Kunchong Shi Wei Xia Shunqing Xu Yuanyuan Li Key Laboratory of Environment and Health(HUST) Ministry of Education&Ministry of Environmental Protectionand State Key Laboratory of Environmental Health(Incubation)School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Epidemiology Brown University School of Public HealthProvidenceRI 02903USA Division of Women’s Health Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonMA 02115USA Department of Biostatistics Brown University School of Public HealthProvidenceRI 02903USA Wuhan Children’s Hospital(Wuhan Maternal and Child Healthcare Hospital) Wuhan 430019China Division of Endocrinology Department of MedicineWarren Alpert Medical School of Brown UniversityProvidenceRI 02903USA

The understanding of the impact of prenatal exposure to metal mixtures on birth weight is limited.We aimed to identify metal mixture components associated with birth weight and to determine additional pairwise interactions between metals showing such associations.Concentrations of 18 metals were measured using inductively coupled plasma mass spectrometry in urine samples collected in the 3rd trimester from a prenatal cohort(discovery;n=1849)and the Healthy Baby Cohort(replication;n=7255)in Wuhan,China.In the discovery set,we used two penalized regression models,i.e.,elastic net regression for main effects and a lasso for hierarchical interactions,to identify important mixture components associated with birth weight,which were then replicated.We observed that 8 of the 18 measured metals were retained by elastic net regression,with five metals(vanadium,manganese,iron,cesium,and barium)showing negative associations with Z-scores for birth weight and three metals(cobalt,zinc,and strontium)showing positive associations.In replication set,associations remained significant for vanadium(β=-0.035;95%confidence interval[CI],-0.059 to0.010),cobalt(β=-0.073;95%CI,0.049 to 0.097),and zinc(β=-0.040;95%CI,0.016 to 0.065)after Bonferroni correction.We additionally identified and replicated a single pairwise interaction between iron and copper exposure on birth weight(P<0.001).Using a two-stage analysis,we identified and replicated individual metals and additional pairwise interactions-associated birth weight.The approach could be used in other studies estimating the effect of complex mixtures on human health.

关键词： prenatal exposure Metal mixture Birth cohort Two-stage analysis

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The Identification of prenatal exposure to Mitragynine Using Umbilical Cord Tissue

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American Journal of Analytical Chemistry 2022年第4期13卷 162-174页

作者： Mary Ellen Wright Donna Coy Joseph Jones Andre Sukta Amy Racines Mary Jones Clemson University School of Nursing Greenville SC USA United States Drug Testing Laboratories Des Plaines USA

Objective: Kratom is widely available and literature exploring the effects of prenatal kratom exposure is lacking. This study aims to report a validated method for the detection of mitragynine in the umbilical cord and report our observations for specimens received at a national commercial reference laboratory. Study Design: Assays were validated according to the recommendations of ANSI/ASB. A retrospective evaluation of records at a national reference laboratory was conducted to determine prevalence and co-exposure to other substances of abuse. Result: Mitragynine was detected in 19 of 4456 specimens (0.43%) with concentrations ranging from 4 to >50 ng/g. Thirteen (13) of these specimens were positive for only mitragynine while the other 6 were also positive for either marijuana or opiates. Conclusion: Umbilical cord is a suitable specimen type for the surveillance of maternal kratom use and can be used to identify exposed neonates for further investigations into short- or long- term health consequences.

关键词： Kratom Mitragyna Speciose Mitragynine Umbilical Cord prenatal exposure Maternal Drug Use

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Maternal cigarette smoking during pregnancy and reproductive health in children： a review of epidemiological studies

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Asian Journal of Andrology 2014年第1期16卷 39-49页

作者： Linn Berger Hfikonsen Andreas Ernst Cecilia Host Ramlau-Hansen Department of Public Health Section for Epidemiology Aarhus University Aarhus Denmark

Maternal cigarette smoking may affect the intrauterine hormonal environment during pregnancy and this early fetal exposure may have detrimental effects on the future trajectory of reproductive health. In this review, we discuss the epidemiological literature on the association between prenatal exposure to maternal cigarette smoking and several aspects of reproductive health. The literature points towards an increased risk of the urogenital malformation cryptorchidism, but a potential protective effect on the risk of hypospadias in sons following prenatal cigarette smoking exposure. Studies on sexual maturation find a tendency towards accelerated pubertal development in exposed boys and girls. In adult life, prenatally exposed men have impaired semen quality compared with unexposed individuals, but an influence on fecundability, that is, the biological ability to reproduce, is less evident. We found no evidence to support an association between prenatal cigarette smoking exposure and testicular cancer. Among adult daughters, research is sparse and inconsistent, but exposure to cigarette smoking in utero may decrease fecundability. In conclusion, prenatal exposure to cigarette smoking may cause some long-term adverse effects on the reproductive health.

关键词： fertility prenatal exposure puberty testicular neoplasms time-to-pregnancy

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Evaluation of spermatogenesis and fertility in F1 male rats after in utero and neonatal exposure to extremely low frequency electromagnetic fields

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Asian Journal of Andrology 2005年第2期7卷 189-194,页

作者： M.K.Chung S.J.Lee Y.B.Kim S.C.Park D.H.Shin S.H.Kim J.C.Kim Reproductive Toxicology Division Korea Institute of ToxicologyKorea Research Institute of Chemical TechnologyDaejeon 305-600Korea College of Veterinary Medicine Chungbuk National UniversityCheongju 361-763Korea College of Veterinary Medicine Kyungpook National UniversityDaegu 702-701Korea College of Veterinary Medicine Chonnam National UniversityGwangju 500-757Korea

Aim:To determine whether in utero and neonatal exposure to a 60 Hz extremely low frequency electromagnetic field (EMF) results in spermatotoxicity and reproductive dysfunction in the F1 offspring of rats.Methods:Age-matched, pregnant Sprague-Dawley rats were exposed continuously (21 h/day) to a 60 Hz EMF at field strengths of 0 (sham control),5,83.3 or 500 μT from day 6 of gestation through to day 21 of lactation.The experimentally generated magnetic field was monitored continuously (uninterrupted monitoring over the period of the study) throughout the study.Results:No exposure-related changes were found in exposed or sham-exposed animals with respect to the anogenital distance,preputial separation,testis weight,testicular histology,sperm count,daily sperm production, sperm motility,sperm morphology and reproductive capacity of F1 offspring.Conclusion:exposure of Sprague- Dawley rats to a 60 Hz EMF at field strengths of up to 500 μT from day 6 of gestation to day 21 of lactation did not produce any detectable alterations in offspring spermatogenesis and fertility.

关键词： spermatogenesis electromagnetic fields prenatal exposure postnatal exposure rat

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Pyridoxal 5'-phosphate alleviates prenatal pyridaben exposureinduced anxiety-like behaviors in offspring

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Environmental Science and Ecotechnology 2023年第1期13卷 125-133页

作者： Xingwang Ding Ya Wen Xuan Ma Yuepei Zhang Yuting Cheng Zhaofeng Liu Weiyue Hu Yankai Xia State Key Laboratory of Reproductive Medicine Center for Global HealthSchool of Public HealthNanjing Medical University101 Longmian AvenueJiangning DistrictNanjing211166China Key Laboratory of Modern Toxicology of Ministry of Education School of Public HealthNanjing Medical University101 Longmian AvenueJiangning DistrictNanjing211166China Department of Chronic Non-Communicable Disease Control Wuxi Liangxi District Center for Disease Control and PreventionWuxi214011China Department of Nutrition and Food Safety School of Public HealthNanjing Medical UniversityNanjing211166China

Pyridaben(PY)is a widely used organochlorine acaricide,which can be detected in the peripheral blood of pregnant women.Available evidence suggests that PY has reproductive toxicity.However,it remains uncertain whether prenatal PY exposure impacts neurobehavioral development in offspring.Here,we administered PY to pregnant mice at a dose of 0.5 and 5 mg kg^(-1)day^(-1)via gavage and observed anxietylike behaviors in PY offspring aged five weeks.We then integrated the metabolome and transcriptome of the offspring's brain to explore the underlying mechanism.Metabolome data indicated that the vitamin B6 metabolism pathway was significantly affected,and the pyridoxal 50-phosphate(PLP)concentration and the active form of vitamin B6 was significantly reduced.Moreover,the transcriptome data showed that both PLP generation-related Pdxk and anxiety-related Gad1 were significantly down-regulated.Meanwhile,there was a decreasing trend in the concentration of GABA in the hippocampal DG region.Next,we supplemented PLP at a dose of 20 mg kg^(-1)day^(-1)to the PY offspring via intraperitoneal injection at three weeks.We found up-regulated expression of Pdxk and Gad1 and restored anxiety-like behaviors.This study suggests that prenatal exposure to PY can disrupt vitamin B6 metabolism,reduce the concentration of PLP,down-regulate the expression levels of Pdxk and Gad1,inhibit the production of GABA,and ultimately lead to anxiety-like behaviors in offspring.

关键词： Pyridaben prenatal exposure Pyridoxal 50-phosphate Anxiety-like behaviors

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Pulmonary hypertension in extremely low birth weight infants:characteristics and outcomes

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World Journal of Pediatrics 2014年第1期10卷 46-52页

作者： Wambui Waruingi Maroun Jean Mhanna Department of Pediatrics Division of NeonatologyMetro Health Medical CenterCase Western Reserve University School of MedicineClevelandOH 44109USA

Background:To determine the characteristics and outcomes of pulmonary arterial hypertension(PAH)in extremely low birth weight(ELBW)infants.Methods:A retrospective case-control study of all ELBW infants admitted to a level III neonatal intensive care unit(NICU)between January 1,2003 and December 31,2010.Results:During the study period,450 ELBW infants were admitted.6.4%(29/450)were diagnosed with PAH and were matched to 26 controls.The mean gestational age of infants with PAH and their controls were similar[24.5±1.3 vs.24.9±1.8 weeks(P=0.26)];however the cases were smaller at birth than were controls[640.7±119.5 vs.727.0±184.5 g(P=0.04)].The diagnosis of PAH was made at a mean postnatal age of 131.8±53.7 days.Infants with PAH had a higher rate of intrauterine exposure to illicit maternal drug use[12/29(41%)vs.1/25(4%);P=0.001],a longer duration of initial mechanical ventilation[74.9±28.3 vs.59.1±27.8 days;(P=0.04)],a higher incidence of severe BPD[23/29(79%)vs.13/26(50%);P=0.02],and a greater NICU mortality rate[12/29(41%)vs.4/26(15%);P=0.04].Conclusion:PAH in ELBW infants is associated with maternal illicit drug use in pregnancy,longer exposure to mechanical ventilation,severe bronchopulmonary dysplasia and a significant increase in early mortality.

关键词： bronchopulmonary dysplasia echocardiography illicit drug use mechanical ventilation prenatal exposure

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Has Sperm Count Declined in the General Male Danish Population during the Last Several Decades?A Study on the Relation of Sperm Count and Birth Year

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Journal of Reproduction and Contraception 1997年第1期8卷 45-55页

作者：郑晔丁训诚 BondeJensPeter ErnstErik MortensenJensTolbol EgenseJohan NotionalEvaluationCentreforToxicologyofFertilityRegalatingDrugs Shanghai200032P.R.China TheSTENOInstituteofPublicHealth UniversityofAarhusDenmark DepartmentofOccupationalMedicine HospitalofAalborgAalborgDenmark DepartmentofClinicalChemistry SonderborgSygehusSonderborgDenmark

It has been hypothesized that during the last several decades human sperm count has declined because of prenatal exposure to environmental chemicals. We examined the relation between semen quality and birth year among 8608 men born from 1922 to 1971 and who from 1968 to 1992 consulted 4 Danish medical centers because of barren marriage. Data were obtained from medical records and by a postal questionnaire to a subset of the population. The sperm concentration was significantly declining with increasing year of birth in 2 of the 4 centers, but this association disappeared when confounders were adjusted for. Within the subset of men born during 1955~1970 comprising 36% of the entire population we revealed a decrease of the average sperm concentration by 1.6 million /ml (95% CI:0.7~2.5) per one advancing year of birth.This finding was consistent across all the 4 centers and robust to adjustment for effects of calendar period, season and duration of sexual abstinence. Effects of age were accounted for by restriction of the sample to men between 20 and 45 years. The findings are compatible with environmental impact in the prenatal period after 1955 but are far from unequivocal evidence that the sperm count in the general male Danish population has changed during the past decades.

关键词： Sperm count prenatal exposure Secular trend Fertility,Birth year

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Developmental nicotine exposure impair proliferation and survival of hippocampal neural cells in adolescent offspring mice

Developmental nicotine exposure impair proliferation and sur...

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中国神经科学学会第十二届全国学术会议

作者： Fei LIU Di-Qing WU Yu-Ting HU Hui YANG Xin-Rong TAO Center for Medical research Medical School Anhui University of Science and Technology Department of Biochemistry and Molecular Biology Medical School Anhui University of Science and Technology

Smoking addiction during pregnancy is still an important health problem. It associates with variety of brain impairment in the offspring including cognitive deficits, anxiety disorders and attention deficit hyperactivity disorder. The underlying mechanism of hippocampal modulation remains elusive. Objective The purpose of this study is to investigate the proliferation and survival of hippocampal neural cells in mouse offspring of nicotine exposure during pre-pregnancy, pregnancy and breastfeeding. Methods 7-weeks-old C57 BL/6 female mice were administrated with nicotine（200 μg/ml in 2% saccharin） via drinking water starting from 2 weeks pre-mating until the offspring were weaned, while control female mice were received 2% saccharin. Locomoter activity and anxiety-like behavior were analyzed by open field test in adolescent offspring（P35）. 5-Bromo-2-deoxyuridine（Brd U） intraperitoneal injection was used to detect the proliferation and survival of neural cells in hippocampus. Immunofluorescence staining was performed to colocalize Brd U/Neu N, Brd U/GFAP or Brd U/Iba-1 double positive neural cells. Results（1） Total distance and immobility within one hour showed no significant difference in the open field between nicotine and control group. However, the exploration time in the center of the open field reduced remarkly in both male and female adolescent offspring mice of nicotine group compared to the control（P ＜ 0.05）.（2） Both male and female mice in nicotine offspring group showed less newborn neurons relative to the control（P ＜ 0.05）.（3） We found that offspring male mice in nicotine group had more Brd U positive neurons（Neu N+/Brd U+） in the dentate gyrus compared to the female ones although no statistic difference was detected. Surprisingly, nicotine offspring male mice exhibited more Brd U positive（GFAP+/Brd U+ and Iba1+/Brd U+） neuroglia in CA1 and CA2 region than nicotine female ones. Conclusion These results suggest that developmental nicotine exposure contributed to adolescent anxiety-like behavior in offspr

关键词： Nicotine neurotoxicity Neural development Hippocampal neural cells Cell proliferation and survival Children’s disorders prenatal exposure Animal model

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Maternal endotoxemia results in increases in blood pressure and body weight in rats

Maternal endotoxemia results in increases in blood pressure ...

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两岸三地药理学与临床药理学术会议

作者： WEI Yan-ling LI Xiao-hui (Institute of Materia Medica, School of Basic Medicine, Third Military Medical University, Chongqing 400038, China)

Objective To investigate the effects of prenatal exposure to lipopolysaccharide (LPS) on blood pressure and body weight of offspring in rats.Methods Sixteen healthy pregnant rats were randomly divided into two groups.The rats in LPS group were injected intraperitoneally with LPS (0.79 mg·kg) at the 8,10,12 day of gestation.Those in the control group were only treated with NS.After delivery,all off- spring were weighed and blood pressure was measured by tail-cuff method once every two weeks from the 6 to 24 week.In the 15 week,their food intakes were weighed every day.At the end of the 24 week, the rats were put to death by decapitation.Abdominal adipose tissues were taken to weigh,and serum level of leptin was detected by RIA.Results The offspring with prenatal LPS exposure showed increased systemic arterial pressure,heavier body weight,elevated food intake,increased adipose tissue weight and increased circulating leptin compared with controls.Conclusions prenatal exposure to LPS leads to increases in blood pressure and body weight in rats.

关键词： hypertension inflammation obesity prenatal exposure

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