The combined effects of MRI and X-rays on ICR mouse embryos during organogenesis

The combined effects of X-rays and magnetic resonance imaging (MRI) on mouse embryos at an early stage of organogenesis were investigated. Pregnant ICR mice were irradiated on day 8 of gestation with X-rays at a dose of 1 Gy and/or MRI at 0.5 T for 1 hour. The mortality rates of the embryos or fetuses, the incidence of external malformations, the fetal body weight and the sex ratio were observed at day 18 of gestation. A significant increase in embryonic mortality was observed after exposure to either 1 Gy of X-radiation or 0.5 T MRI. However, the combined X-rays and MRI did not show a statistically significant increase in embryonic mortality compared with the control. External malformations, such as exencephaly, a cleft palate and anophthalmia, were observed in mice irradiated with X-rays and/or MRI. The incidence of each malformation in all treated groups increased with statistical significance compared with the control mice. The incidence in mice irradiated with both X-rays and MRI was lower than in mice irradiated with only X-rays. The combined effects of the combination of radiation and MRI on the external malformations might be antagonistic. There were no statistically significant differences in fetal death, fetal body weight and sex ratio among all experimental groups.     

Effects of prenatal exposure to ionizing radiation

Prenatal exposure to ionizing radiation induces some effects that are seen at birth and others that cannot be detected until later in life. Data from A-bomb survivors in Hiroshima and Nagasaki show a diminished number of births after exposure under 4 wk of gestational age. Although a wide array of congenital malformations has been found in animal experimentation after such exposure to x rays, in humans only small head size (exposure at 4-17 wk) and mental retardation (exposure primarily at 8-15 wk) have been observed. In Hiroshima, small head size occurred after doses of 0.10-0.19 Gy or more, and an excess of mental retardation at 0.2-0.4 Gy or more. Intelligence test scores were reduced among A-bomb survivors exposed at 8-15 wk of gestational age by 21-29 IQ points per Gy. Other effects of in-utero exposure to atomic radiation include long-lasting complex chromosome abnormalities.     

Hydrocephalus in mice following X-irradiation at early gestational stage: possibly due to persistent deceleration of cell proliferation

The pathogenesis of X-ray-induced congenital hydrocephalus was studied. Pregnant mice were irradiated at 1.4 Gy on gestational day 7 (G7). Four hours after irradiation, extensive cell death was evident in the neuroepithelium and underlying mesoderm of the head region, and proliferating cell nuclear antigen (PCNA)-immunoreactive cells almost disappeared. Embryos with thinner lamina terminalis of the telencephalon, when compared with that of the control, were found in the irradiated group on G9. As early as G11 in some irradiated embryos the telencephalic wall was thinner and lateral ventricles were larger than those of the control. The choroid invagination from the lamina terminalis began on G11 in the control brain, but not in the affected brain. During the following development, fetuses with readily apparent hydrocephalus were consistently found among irradiated fetuses. In these brains the brain mantle was thinner, the corpus striatum and thalamic regions were smaller, and lateral ventricles were larger than those of the control. Even on G11 and G13 the frequencies of PCNA-positive cells in the brain mantle and other brain regions were lower in the hydrocephalic brain than those of the control, suggesting a decelerated proliferation of successive cell generations following exposure to X-rays. The cerebral aqueduct was open in the hydrocephalic brain during the fetal period when the lateral ventricles were dilated. The head was vaulted after birth but the cerebral aqueduct was not completely occluded even in these animals. These findings suggested that cell death in the neuroepithelium followed by a persistent deceleration of neural cell proliferation, resulting in the hypoplasia of brain parenchyma with compensatory ventricular dilatation, is important for the establishment of hydrocephalus.     

Effect of "in utero" exposure to low doses of low energy X-rays on the postnatal development of mouse

Pregnant Swiss albino mice were exposed to a single dose of 9 mGy or 50 mGy of 70 kVp X-rays on day 3.5 (preimplantation), 6.5 (early organogenesis) or 11.5 (late organogenesis) of gestation. The offspring were observed for any radiation induced changes in litter size at birth and sex ratio at 4 wks of age, and postnatal mortality and growth retardation up to 6 wks of age. Irradiation at the early organogenesis stage produced an increase in the postnatal death, statistically significant in the 50 mGy group. A significant increase in the number of retarded offspring and decrease in body weight were observed in the groups exposed at the early and late organogenesis periods. The results indicate that a single exposure to low energy low dose X-rays can be harmful to the growing embryos and the type and extent of the injury will depend on the stage of development as well as the dose of radiation.     

Teratogenic effects of lithium and ethanol in the developing fetus

Prolonged administration of either lithium (7 mg/kg body wt.) or ethanol (30% of daily caloric intake) for 10 days to pregnant rats results in several anatomical abnormalities in the fetus. Intragastric administration of lithium carbonate to pregnant rats immediately after confirmation of pregnancy resulted in high incidence of cleft palate, growth retardation, brain liquification and pulpy brain, hepatomegaly and digital abnormalities, when compared to the saline-treated controls. Furthermore, lithium administration during gestation also resulted in other less frequently observed abnormalities in the fetus, e.g., cardiomegaly, hydronephrosis, ankle-joint defects, syndactyly, defected ribs and sternum ossification defects. Chronic ethanol consumption by pregnant rats during early gestation also resulted in several anatomical abnormalities of prenatal growth retardation, resorption and still births, cleft palate, hydrocephaly and hydronephrosis. The severity and frequency of several of the fetal abnormalities were compounded when lithium and ethanol were administered simultaneously. The possible mechanisms of lithium and ethanol teratogenicity and their synergistic effects have been explained on a biochemical basis.     

Maternal Folic Acid Deficiency Is Associated to Developing Nasal and Palate Malformations in Mice

Craniofacial development requires extremely fine-tuned developmental coordination of multiple specialized tissues. It has been evidenced that a folate deficiency (vitamin B₉), or its synthetic form, folic acid (FA), in maternal diet could trigger multiple craniofacial malformations as oral clefts, tongue, or mandible abnormalities. In this study, a folic acid-deficient (FAD) diet was administered to eight-week-old C57/BL/6J female mouse for 2–16 weeks. The head symmetry, palate and nasal region were studied in 24 control and 260 experimental fetuses. Our results showed a significant reduction in the mean number of fetuses per litter according to maternal weeks on FAD diet (p < 0.01). Fetuses were affected by cleft palate (3.8%) as well as other severe congenital abnormalities, for the first time related to maternal FAD diet, as head asymmetries (4.6%), high arched palate (3.5%), nasal septum malformed (7.3%), nasopharynx duct shape (15%), and cilia and epithelium abnormalities (11.2% and 5.8%). Dysmorphologies of the nasal region were the most frequent, appearing at just four weeks following a maternal FAD diet. This is the first time that nasal region development is experimentally related to this vitamin deficiency. In conclusion, our report offers novel discoveries about the importance of maternal folate intake on midface craniofacial development of the embryos. Moreover, the longer the deficit lasts, the more serious the consequent effects appear to be.     

Role of corticosterone in cleft palate formation in methylmercuric chloride-treated mice

The effect of simultaneous administration of sodium selenite and methylmercuric chloride on plasma corticosterone, and the effect of adrenalectomy and methylmercuric chloride treatment on the incidence of fetal cleft palate in mice were examined. After 6 consecutive days of treatment, methylmercury (as methylmercuric chloride) at 5 mg/kg per day increased plasma corticosterone to approximately twice the concentration observed in the controls. When administered together, selenium (as sodium selenite) at 125–135 mg/kg per day did not affect the increase of plasma corticosterone induced by methylmercuric chloride. Selenite by itself (125–135 mg selenium/kg per day) resulted in an increase of approximately 50% over the controls. Sham operation or adrenalectomy of mice on Day 7 of pregnancy did not result in a significant incidence of cleft palate in the fetuses. However, the administration of methylmercury (5 mg/kg per day) on Days 11, 12, and 13 of gestation to the operated mothers resulted in cleft palate in approximately 30% of the fetuses, regardless of the type of operation. The significance of these findings is discussed.     

Effect of sodium selenite on methylmercury-induced cleft palate in the mouse

The effects of simultaneous administration of sodium selenite on the teratogenic action of methylmercury was examined. Methylmercury, or sodium selenite, or a mixture of methylmercury and sodium selenite was administered subcutaneously to pregnant ICR-strain mice on Days 9 through 12 or Days 7 through 12 of gestation, and intraperitoneally to pregnant C57BL-strain mice on Days 7 through 12 of gestation. On Day 17 of gestation the fetuses were removed and examined for cleft palates. Although the incidence of cleft palate in the fetuses, on Day 17, differed according to the concentration of methylmercury (3 or 5 mg/kg/day) and the duration of administration (1 injection per day for 4 or 6 days), the simultaneous administration of selenium at concentrations of 0.0625 to 3.5 mg/kg/day did not reduce the incidence of cleft palate. At the higher concentrations (0.5 to 3.5 mg/kg/day) selenium appeared to increase the maternal toxicity and the teratogenicity of methylmercury. Analysis of fetal body weights on Day 17 of gestation indicated that in those groups in which methylmercury alone resulted in a significant decrease in body weight, the simultaneous administration of selenium did not prevent this growth suppression. It is suggested that cleft palate induction by methylmercury is the result of suppression of growth, rather than a tissue-specific teratogenic action. The effects of methylmercury and selenium on other parameters of maternal and fetal health are also discussed.     

孕期服用叶酸预防和阻止小鼠腭裂的初步研究

目的:探讨叶酸对地塞米松所诱导小鼠腭裂的预防和阻止作用,为唇腭裂的预防提供新的途径。方法:选取NIH系小鼠,分为5组,第1组孕鼠在GD1-15经口灌胃0·6ml的生理盐水,第2、3、4组在GD1-15分别经口灌胃10mg/kg、30mg/kg、60mg/kg的叶酸;第5组在GD13-18经口灌胃60mg/kg的叶酸。5组孕鼠均在GD12腹腔注射50mg/kg醋酸地塞米松。在GD18断颈处死孕鼠,剖腹检查胎鼠吸收和死亡情况,对活的胎鼠检查腭裂发生情况。结果:第1组未用叶酸处理的孕鼠所产胎鼠腭裂的发生率为63·8%;第2组腭裂的发生率为64·9%;第3组腭裂的发生率为58·9%;第4组腭裂发生率为42·3%;第5组腭裂的发生率为65·3%。统计学分析第4组与第1组之间差异有显著性;第2、3、5组与第1组之间差异无统计学意义。结论:只有高剂量的叶酸(60mg/kg)才能降低胎鼠腭裂的发生率;并且要从妊娠的前期开始连续使用,才能达到良好的预防效果。     

Teratogenicity of polybrominated biphenyls in rats.

The teratogenic potential of a mixture of polybrominated biphenyls (PBB) was investigated. Pregnant Wistar albino rats were given single doses of PBB in seasame oil by gavage on one day of pregnancy, from day 6 through 14 (sperm day = 0). The dose ranged from 40 to 800 mg/kg maternal body weight. At autopsy (day 20) fetuses were recovered and subsequently examined for skeletal and soft-tissue abnormalities. Resorptions followed treatment at all days. No skeletal malformations were seen at any dose level. The majority of soft tissue defects were found following 800 mg/kg PBB at day 11, 12, or 13. Only two malformations were produced, cleft palate and diaphragmatic hernia. It is concluded that a single high dose of PBB can be embryolethal and teratogenic to the rat embryo.     

The influence of dietary folate supplementation on the incidence of teratogenesis in zinc-deficient rats

Two studies were conducted to investigate the possibility that pteroylmonoglutamic acid supplementation would alleviate teratogenesis in zinc-deficient rats. Pregnant rats of the Wistar strain were fed on Zn-deficient (less than 0.5 mg Zn/kg) or Zn-supplemented (75 or 95 mg Zn/kg) diets from mating until day 18.5 of gestation. The basal level of pteroylmonoglutamic acid added to all diets (0.56 mg/kg) was supplemented with 30-200 mg/kg in selected diets. Dietary Zn deprivation resulted in fetal resorption, fetal growth retardation and reduced concentrations of Zn in fetuses and maternal plasma and tibia. Low maternal body-weight at conception emerged as an important determinant of risk of resorption in Zn-deficient rats. Dietary Zn deficiency resulted in reduced maternal plasma folate concentrations and these values were inversely correlated with litter size or weight in Zn-deficient rats. Pteroylmonoglutamic acid supplementation increased maternal plasma folate concentrations, but did not reduce the high incidence of teratogenesis which occurred in Zn-deficient rats. Supplementation of Zn-deficient rats with pteroylmonoglutamic acid significantly increased the incidence of clubbed foot and tended to increase the incidence of brain or meningeal abnormalities, or both, and cleft palate, but did not reduce maternal or fetal Zn status. Pteroylmonoglutamic acid supplementation also increased the weights of Zn-supplemented control fetuses.     

Species and strain differences in teratogenic effects of biotin deficiency in rodents

The teratogenicity of maternal biotin deficiency of mice, rats and Syrian hamsters was compared. Biotin deficiency during pregnancy caused severe malformations and growth retardation in mouse fetuses. The malformations were mainly cleft palate, micrognathia, micromelia and open eyelid. The ICR and C57BL strains of mice were more susceptible than the A/Jax strain to biotin deficiency. In rats, no malformations were seen in the fetuses from biotin-deficient dams. In hamsters, embryonic lethality was very high in biotin-deficient dams, and teratogenicity of biotin deficiency was rather equivocal. The results of measurements of the maternal and fetal biotin content suggest that a possible underlying mechanism is a difference in the efficiency of the mother-to-fetus transport of biotin among these species.     

The embryotoxic response produced by inorganic mercury in different strains of hamsters

This report compares the mercury-induced embryotoxicity among one noninbred (LVG) and five inbred (CB, LHC, LSH, MHA, PD4) strains of hamsters. A single dose of mercuric acetate (15 mg/kg, sc) was injected into pregnant hamsters on the morning of the 8th gestation day. Treated and control animals were killed on either the 12th or 15th gestation day and studied for the types and frequency of external and internal abnormalities as well as the incidence of resorption sites. The hamster strains exhibited significant resorption rates as well as a variety of abnormalities including edema, retardation, ventral wall defects, pericardial cavity distention, cleft palate, hydrocephalus, and heart defects. Significant but varied interstrain differences were observed for most of these indicators of mercury-induced embryotoxicity. The results of this study were compared with prior work in which the same hamster strains were exposed to cadmium or lead.     

三维超声在胎儿半椎体诊断中的应用价值

目的:探讨三维超声(3DUS)在胎儿半椎体诊断中的应用及临床价值。方法:回顾性分析诊断的12例胎儿半椎体病例的产前二维超声(2DUS)及3DUS声像图表现,并与引产后影像学检查及病理结果进行对照。结果:3DUS胎儿半椎体的声像图比2DUS更准确直观;12例中单发4例(33.3%),合并其他系统畸形8例(66.7%),分别是泌尿系统畸形4例,心脏畸形2例,单脐动脉2例,肠道闭锁、肺囊腺瘤样病变、唇腭裂、双足内翻各1例。结论:3DUS对胎儿半椎体及其相关畸形的诊断是较准确的,具有显著的临床价值。     

以形态与组织学为基础筛选诱导胎鼠腭裂的四氯二苯二噁英最适剂量

目的观察在不同四氯二苯二噁英(TCDD)剂量的作用下,胎鼠腭裂形成过程中的形态学、组织学变化,以筛选TCDD诱导腭裂模型的最适剂量。方法C57BL/6J孕鼠于妊娠第10天随机分为对照组和实验Ⅰ～Ⅳ组,每组6只;对照组以玉米油0.1ml灌胃,实验Ⅰ、Ⅱ、Ⅲ、Ⅳ组分别以TCDD32、28、24、20μg/kg灌胃。妊娠第17.5天处死孕鼠,称量孕鼠及胚胎体重,记录活胎鼠数、腭裂数、吸收胎及死胎鼠数。另取15只C57BL/6J孕鼠随机分组同前,处理方法同前;各组分别于妊娠第13.5、14.5和15.5天剪取胎鼠头部,解剖显微镜下观察;并行苏木精-伊红染色(HE染色),观察。结果各组孕鼠增加的体重及活胎鼠的体重差异均无显著性。Ⅰ、Ⅱ、Ⅲ组较对照组双侧腭突发育瘦小,上抬延迟;Ⅳ组双侧腭突发育及上抬与对照组相比无明显差异。Ⅰ～Ⅳ组胎鼠腭裂发生率分别为97.37%、93.02%、65.12%、56.82%,对照组未见胎鼠腭裂形成。结论 TCDD28μg/kg是建立C57BL/6J胎鼠腭裂模型的最适剂量。     

Prenatal radiation exposure: background material for counseling pregnant patients following exposure to radiation

Fetal sensitivity to radiation-induced health effects is related to gestational age, and it is highly dependent on fetal dose. Typical fetal doses from diagnostic radiology are usually below any level of concern. Although rare, significant fetal radiation doses can result from interventional medical exposures (fluoroscopically guided techniques), radiation therapy, or radiological or nuclear incidents, including terrorism. The potential health effects from these large radiation doses (possibly large enough to result in acute radiation syndrome in the expectant mother) include growth retardation, malformations, impaired brain function, and neoplasia. If exposure occurs during blastogenesis (and the embryo survives), there is a low risk for congenital abnormalities. (In all stages of gestation, radiation-induced noncancer health effects have not been reported for fetal doses below about 0.05 Gy [5 rad].) The additional risk for childhood cancer from prenatal radiation exposure is about 12% per Gy (0.12%/rad) above the background incidence.     

Maternal smoking, genetic variation of glutathione s-transferases, and risk for orofacial clefts

BACKGROUND: Maternal smoking is a known risk factor for orofacial clefts. We investigated whether risk is greater among offspring who lack the genetic capacity to produce glutathione S-transferase enzymes relevant to detoxification of chemicals in cigarette smoke. METHODS: Using a population-based case-control design, we genotyped 423 California infants with an isolated cleft and 294 nonmalformed controls for null variants of the glutathione S-transferases GSTT1 and GSTM1. RESULTS: If a mother smoked during pregnancy and her fetus was homozygous null for GSTT1, the risk of isolated cleft lip with or without cleft palate was tripled (odds ratio = 2.9; 95% confidence interval = 1.2-7.2). For fetuses who were homozygous null for GSTM1 and whose mothers smoked >/=20 cigarettes per day, we found nearly a 7-fold increased risk (6.8; 0.82-57). Combined absence of GSTM1 and GSTT1 enzymes among the offspring of smoking mothers was associated with a nearly 6-fold increased risk for cleft lip (6.3; 1.3-42). A similar increased risk for cleft palate was associated with absence of GSTM1, but not for absence of GSTT1. CONCLUSIONS: Maternal smoking during pregnancy increases risks for clefts among fetuses lacking enzymes involved in the detoxification of tobacco-derived chemicals.     

18-三体综合征胎儿的产前超声筛查

目的:评价18三体综合征胎儿的超声表现特征和产前超声筛查的价值。方法:对羊膜腔穿刺或脐血管穿刺确诊为18-三体综合征的27例胎儿超声声像图进行分析。结果:27例18-三体胎儿均表现为胎儿结构异常,每例胎儿可检出四项及四项以上超声异常,最常见的超声改变是心脏畸形,共25例;其它常见的异常包括重叠指17例,单脐动脉11例,小下颌10例,上消化道梗阻9例,脉络丛囊肿及桡骨发育不良或缺如各8例,草莓头7例,小脑发育不良、小脑延髓池扩大、脐膨出及腕关节异常各6例,宫内生长受限11例,羊水过多19例。结论:超声检查是产前筛查18-三体综合征胎儿的有效手段。     

妊娠期高血压患者在晚孕期胎儿心脏Tei指数的改变

目的:研究妊娠期高血压疾病(HDCP)患者于晚期妊娠期不同胎龄胎儿心脏Tei指数的变化。方法:应用超声心动图测量41例HDCP患者的胎儿(28～32周,32+1～36周)和41例与其胎龄匹配的正常胎儿的心脏多普勒时间间期,计算左、右心室Tei指数范围,分析不同胎龄胎儿心室Tei指数间有无统计学差异。结果:晚期妊娠中胎儿胎龄不同,其心脏Tei指数改变亦不同,病例组与对照组胎龄为28～32周的胎儿左、右心室Tei指数比较,右心室Tei指数病例组高于对照组,差异具有统计学意义(P<0.05),病例组与对照组胎龄为32+1～36周的胎儿左、右心室Tei指数比较,病例组胎儿左、右心室Tei指数均高于对照组,差异具有统计学意义(P<0.05)。结论:妊娠期高血压疾病(HDCP)患者于晚期妊娠期胎儿心脏Tei指数改变与HDCP患者胎儿胎龄有关。     

超声容积断层显像技术在胎儿唇腭裂诊断中的价值

目的探讨超声容积断层显像技术在胎儿唇腭裂诊断中的价值,以提高超声对胎儿唇裂、唇裂合并腭裂的检出率。方法采用SIEMENS ACUSON Antares超声诊断仪对33例产前二维超声诊断为唇裂及唇裂合并腭裂可疑的胎儿进行多切面扫查,同时采集经正中矢状切面胎儿颜面部的三维容积数据进行保存,应用三维后处理功能Multi Slice超声容积断层显像技术对容积数据进行处理分析。结果 33例产前超声诊断为唇裂及唇裂合并腭裂可疑的胎儿均获得较满意的超声容积断层图像,其中单侧唇裂3例,双侧唇裂合并双侧腭裂5例,单侧唇裂合并牙槽突裂7例,单侧唇裂合并双侧腭裂2例,单侧唇裂合并单侧腭裂14例,正中唇裂合并正中腭裂1例,漏诊1例单纯软腭裂。所有病例经产后和引产证实。结论超声容积断层显像技术是诊断胎儿唇腭裂特别是腭裂有效的方法。