Visceral heterotaxy syndrome causes abnormal arrangement of thoracoabdominal organs and severe complex cardiac anomalies by abnormal laterality. The purpose of the present study is to analyze the incidence and pattern of heterotaxy syndrome in etretinate and all-tran retinoic acid treated pregnant DDY mice. Pregnant DDY mice were intragastrically given a single dose of 15 mg/kg of etretinate at day 6, 7 of gestation, 30 mg/kg of etretinate at day 7 of gestation and 20 mg/kg of all-trans retinoic acid at day 7 of gestation. The incidence of visceral heterotaxy was highest in the etretinate 15 mg/kg treated group on day 7 of gestation (38.5%). The major cardiovascular anomalies in heterotaxy syndrome were common atrium, common atrioventricular valve, atrioventricular septal defect, transposition of great arteries, pulmonary atresia, pulmonary artery hypoplasia and aortic arch anomalies. Atrial situs of heterotaxy syndrome were right isomerism, solitus-like, inversus-like and left atrial aplasia, but right isomerism was observed most frequently. The results suggest that retinoic acid exerts a significant effect on the determination of atrial situs during the development of mouse embryo.
*Abnormalities, Drug-Induced ; Animal ; Blood Vessels/abnormalities ; Female ; Heart Defects, Congenital/chemically induced ; Mice ; Pregnancy ; Syndrome ; Tretinoin/*toxicity

The pharmaceutical ethynylestradiol (EE) is a potent endocrine modulator. Application enlargement of ethynylestradiol in clinics and abuse in livestock farming and fishing make it important to explore ethynylestradiol toxicological action on vertebrate embryonic development and to establish an in vivo method for EE toxicity detection efficiently and conveniently. In the present study, using a model animal zebrafish and 17alpha-ethynylestradiol as a representative compound, we have investigated EE2 teratogenicity, target tissues and target genes on zebrafish embryo. The results show that median teratogenesis concentration (TC50) of EE2 is 0.8 microg x mL(-1), and median lethal dose (LD50) is 3.3 microg x mL(-1). Targets of EE2 action were implicated in brain, eyes, heart, muscle, skeleton, pigment and viscera. Embryonic cardiac arrhythmia caused by EE2 is probably resulted from heart abnormal structure. The embryonic stage sensitive to EE2 mainly started at cleavage and last up to the organogenesis with time-accumulating effect. RT-PCR results indicate that EE2 treatment disturbed gene expression pattern at the early period of zebrafish embryonic development by suppressing transcription of gene boz that promotes brain development, upregulating genes for trunk and tail, such as ntl, spt, shh, and perturbing Nodal signal expression of TGFbeta superfamily, for example, cyc, sqt and oep. Using zebrafish, an efficient in vivo method for quick evaluation of EE toxicity on embryonic development has been developed.
Abnormalities, Drug-Induced ; etiology ; Animals ; Arrhythmias, Cardiac ; chemically induced ; embryology ; Dose-Response Relationship, Drug ; Embryo, Nonmammalian ; abnormalities ; drug effects ; Embryonic Development ; drug effects ; Ethinyl Estradiol ; administration & dosage ; toxicity ; Gene Expression Regulation, Developmental ; Teratogens ; toxicity ; Zebrafish ; abnormalities ; embryology

The use of antiepileptic drugs in pregnancy always presents challenges to doctors and their patients as it may have deleterious effects on the developing embryo. Lamotrigine is most commonly-prescribed drug among the newer antiepileptic drugs; hence, it has been selected for the present review. A number of studies pertaining to the safety of lamotrigine use during pregnancy have been reported, with differing results. Contradictory results have been reported in animals regarding lamotrigine teratogenicity, and human studies have also proven inconclusive. In many countries, human pregnancy registries are maintained to establish the safety of antiepileptic drugs during pregnancy, as all the different suggestions favour some over others, with specific antiepileptic combinations still being questioned. It is our hope that the present work may integrate the available disparate relevant facts into a directed effort towards minimising the risk of foetal compromise.
Abnormalities, Drug-Induced ; Animals ; Anticonvulsants ; adverse effects ; therapeutic use ; Epilepsy ; drug therapy ; Female ; Folic Acid Deficiency ; chemically induced ; Humans ; Pregnancy ; Teratogens ; pharmacokinetics ; pharmacology ; Triazines ; adverse effects ; therapeutic use

Warfarin is an oral anticoagulant which is known to cross the placenta causing birth defects, known as warfarin embryopathy; fetal effects of early gestational exposure to warfarin is known to cause marked nasal hypoplasia, rhizomelia, and stippled epiphyses. The period of greatest sensitivity is 6 to 9 weeks of gestational age. Clinical studies have suggested that discontinuing warfarin before 6 weeks of gestational age could avoid the teratogenic effect. We experienced a women who had been taking warfarin for 15 years because of SLE (Systemic Lupus Erythematosus) and CRF (Chronic renal failure), who was found to be pregnant at 9 weeks of gestation. She discontinued warfarin and started heparin treatment, however the ultrasound examination showed shortened long bone, scalp edema, and cardiac anomaly (Ventricular septal defect), and termination of pregnancy was performed at 17 weeks of gestation. We report a case of warfarin embryopathy resulting from warfarin exposure until 9 weeks of gestation with a brief review of literature.
Abnormalities, Drug-Induced ; Chondrodysplasia Punctata ; Congenital Abnormalities ; Edema ; Female ; Fetal Diseases ; Gestational Age ; Heparin ; Humans ; Morphinans ; Nasal Bone ; Placenta ; Pregnancy ; Scalp ; Warfarin

Metabonomics approach is a science that systematically studies the regularity of changes of metabolites and reveals the nature of metabolic activities of the lives in the dynamic process of metabolism. In this study, pregnant C57BL/6J mice were randomly divided into two groups with 15 mice in each. The ones in the experimental group were intraperitoneally injected with Dexamethasone and the others in the control group with isotonic Na chloride from 10th to 12th day of gestational period. On 17.5th day, all the mice were executed. The livers were extracted and prepared into aqueous soluble liver tissue extracts. The technology of nuclear magnetic resonance (NMR) was used to detect the endogenous small molecule metabolites. Finally, through the method of principal component analysis (PCA), changes of metabolites ingredients could be determined. The experimental results showed that there was significant difference in PCA scores plot between the two groups. Furthermore, the difference was in line with that of incidence of cleft palate in the embryos between the two groups. Therefore, metabonomics results can be used to reflect the changes of metabolites group interfered by Dexamethasone in the course of pregnancy of C57BL/6J mice and this method opens up a new way for further study of pathogenic mechanism of cleft lip with or without palate.
Abnormalities, Drug-Induced ; etiology ; metabolism ; Animals ; Cleft Palate ; chemically induced ; Dexamethasone ; toxicity ; Embryo, Mammalian ; Female ; Magnetic Resonance Spectroscopy ; methods ; Metabolomics ; Mice ; Mice, Inbred C57BL ; Pregnancy

Isotretinoin is a known human teratogen that can cause multiple malformations. At present, women who conceive one cycle after discontinuing isotretinoin are told that their teratogenic risk is not higher than baseline. We present a case of both ear malformation in a newborn whose mother had taken isotretinoin for 2 years until one month prior to the time when she became pregnant. We suggest that further studies of pharmacokinetics and malformation of isotreinoin are needed.
Abnormalities, Drug-Induced/*diagnosis/*etiology/pathology ; Adult ; Female ; Humans ; Infant, Newborn ; Isotretinoin/*adverse effects ; Male ; Pregnancy ; *Prenatal Exposure Delayed Effects

OBJECTIVEThe aim of the present study was to investigate the effects of paternal Di-N-butyl-phthalate (DBP) exposure pre- and postnatally on F1 generation offspring, and prenatally on F2 generation offspring.

METHODSMale mice were exposed to either 500 mg/kg or 2 000 mg/kg of DBP for 8 weeks, and mated with non-exposed females. Three-quarters of the females were sacrificed a day prior to parturition, and examined for the number of living and dead implantations, and incidence of gross malformations. Pups from the remaining females were assessed for developmental markers, growth parameters, as well as sperm quantity and quality.

RESULTSThere were no changes in the fertility of parents and in intrauterine development of the offspring. Pups of DBP-exposed males demonstrated growth-retardation. Following paternal exposure to 500 mg/kg bw of DBP, there were almost twice the number of males than females born in the F1 generation. F1 generation females had a 2.5-day delay in vaginal opening. Paternal exposure to 2 000 mg/kg bw of DBP increased the incidence of sperm head malformations in F1 generation males; however, there were no changes in the fertility and viability of foetuses in the F2 generation.

CONCLUSIONPaternal DBP exposure may disturb the sex ratio of the offspring, delay female sexual maturation, and deteriorate the sperm quality of F1 generation males.

Abnormalities, Drug-Induced ; Animals ; Dibutyl Phthalate ; toxicity ; Female ; Male ; Mice ; Paternal Exposure ; adverse effects ; Plasticizers ; toxicity ; Pregnancy ; Sex Ratio ; Sexual Development ; drug effects ; Sperm Head ; drug effects ; pathology

Abnormalities, Drug-Induced ; etiology ; Abnormalities, Radiation-Induced ; etiology ; Antineoplastic Agents ; adverse effects ; Breast Neoplasms ; diagnosis ; therapy ; Contraindications ; Female ; Humans ; Mastectomy ; Neoplasm Staging ; Pregnancy ; Pregnancy Complications, Neoplastic ; diagnosis ; therapy ; Prognosis ; Radiotherapy ; adverse effects ; Risk Assessment ; Risk Factors ; Sentinel Lymph Node Biopsy

OBJECTIVETo explore the possible correlations between clinical and experimental pathological changes of congenital clubfoot and the pathodynamic developmental procedure.

METHODSEighty-three female Wistar rats were administered with retinoic acid on the 10th day after pregnancy. And from February 2001 to February 2004, 48 patients were analyzed with electropysiological examination.

RESULTSThere was clubfoot-like deformity in 53.7% of the experimental fetuses. Persistence of the embryonic position of the talus and tibia in fetuses was observed. Poor overlapping between talus and calcaneus was seen. Cell apoptosis at the anterior corner of spinal cord were seen. Of all the patients, 68.3% were abnormal with electropysiological examination. The pathological sites were frequently localized in lumbarsacral region.

CONCLUSIONCongenital clubfoot is correlated closely with defects of neural tube and spinal cord.

Abnormalities, Drug-Induced ; pathology ; physiopathology ; Animals ; Anterior Horn Cells ; drug effects ; physiology ; Apoptosis ; drug effects ; Child ; Child, Preschool ; Clubfoot ; chemically induced ; pathology ; physiopathology ; Female ; Humans ; Infant ; Pregnancy ; Rats ; Rats, Wistar ; Tretinoin ; pharmacology

Decabromodiphenylethane (DBDPE) has been widely used as an alternative flame retardant due to the restriction or phase-out of traditional polybrominated diphenyl ethers (PBDEs), and is of increasing concern regarding its ubiquity, persistence, and potential adverse effects. In the present study, the toxicological effects of DBDPE were evaluated using zebrafish as an in vivo model. Upon being exposed to DBDPE-polluted sediments for a short term, it was found that the mortality and malformation of zebrafish (including edema, bent notochord, and bent tail) were not affected even at the highest concentration tested (1000.0 µg/kg dry sediment). Regarding behavioral responses, it was found that zebrafish larvae of 48 hours post fertilization (hpf) in all groups escaped successfully with a touch to the dorsal fin. However, when exposed to the highest DBDPE concentration, the larvae of 120 hpf exhibited significantly smaller distances as compared to the control. Moreover, the results of the acetylcholinesterase (AChE) activity, the expression levels of two important nerve-related genes, and the cell apoptosis all indicated that DBDPE posed low neurotoxicity in embryo-larval zebrafish. The results in this study shed some light on the potential risks of DBDPE in the real environment and highlight the application of the sediment exposure route in the future.
Abnormalities, Drug-Induced ; etiology ; Animals ; Apoptosis ; drug effects ; Behavior, Animal ; drug effects ; Bromobenzenes ; toxicity ; Geologic Sediments ; analysis ; Larva ; drug effects ; Neurotoxicity Syndromes ; etiology ; Water Pollutants, Chemical ; toxicity ; Zebrafish ; embryology