胎兔膈疝模型的制作及人工腹裂对肺发育的影响

目的胎兔膈疝模型进行孕期人工腹裂操作，探讨先天性膈疝宫内减压扩肺治疗的价值。方法新西兰孕兔32只，其中21只孕23d，双角子宫一侧末梢胚胎行膈疝造模，另一侧假手术作对照；另11只孕兔，子宫双侧末梢胚胎孕23d均手术造模，孕26d再次剖宫，一侧膈疝兔进行人工腹裂，另一侧仅打开羊膜腔，共得4组胎兔：假手术组（CR组）、膈疝组（DH组）、膈疝无腹裂组（CGS组）、膈疝合并腹裂组（GS组）。分别进行肝、肺重量及轴向腺泡计数（RAC）、终末支气管密度（MTBD）、肺泡相应区域面积（S%）、肺小动脉中膜厚度百分比（MT％）等病理学指标检测。结果①CR组肺湿重／体重（Lw／Bw）为（0．0262±0．005）、RAC（3．17±1．00）个、MTBD（3．42±1．20）个、S％（58．12±11．80）％。DH组和CGS组较CR组Lw／Bw、RAC、S%均明显减少，MTBD、MT％增加。GS组肺发育各项指标和MT％与DH组、CGS组比较无显著差异；②GS组、DH组、CGS组中肝脏重量／体重（Hw／Bw）相对CR组明显增加（P〈0．05），Hw／Bw与Lw／Bw比呈一定负性关系，但未能显示统计学上差异（R=0．2，Y=0．0513X＋0.024）。结论胎兔膈疝模型存在肺发育不良，人工腹裂不能改善肺发育不良，肝脏的主动长入是肺受压的主要因素。     

兔胎仔部分取出宫腔外模型制作可行性研究

目的 探讨将兔胎仔部分取出官腔外，制作动物模型的可行性及方法。方法 取16只日本长耳大白兔孕兔，体重2．6～4.0kg，于孕22d行宫内手术，每只母兔选一远离子宫颈的胎仔，将其部分取出宫腔外，切除一侧下腹壁皮肤、皮下及部分肌肉组织后，放回子宫．术后密切观察母兔有无流产，术后第8d以剖宫产方式取出胎仔，观察手术胎仔的存活情况。结果 16只母兔．2只术后1d内死于气温过高。其余14只母兔均存活至妊娠足月，无一流产。14只手术胎仔在剖宫产时存活9只。手术胎仔存活率64．3％。结论 通过本实验方法，将兔胎仔部分取出宫腔外手术，制作相对复杂的动物模型是可行的。     

大鼠腹裂模型肠管损伤的研究

目的研究先天性腹裂的肠管受损害情况，探讨该病术后并发症的原因。方法利用大鼠腹裂模型，运用组织学、生化学和免疫组织化学方法，分析腹裂胎鼠肠管的组织结构，DNA和蛋白质，细胞增生和凋亡等方面的改变。结果共获得腹裂胎鼠16只，对照胎鼠21只。与对照组相比，腹裂鼠肠管变短、充血水肿、粘连，肠壁表面纤维覆盖，壁内胶原沉积，DNA总量下降，蛋白质总量基本不变，细胞增生率下降，凋亡率上升。结论腹裂的肠管损伤是多方面的，是术后肠管运动和吸收功能异常的原因，大鼠的腹裂模型是对先天性腹裂的病因、病理等方面研究的合适工具。     

羊小肠锁模型的制作及宫内再通手术

对胎龄２．５－３个月的２０只绵羊胎仔制作小肠闭锁模型（正式实验１４只），同时对其中的５只实验胎仔实施宫内再通手术。模型成功率１０／１４，再通手术成功４只。对小肠闭模型中形成的粗大段的病理改变进行了讨论。     

胎羊小肠闭锁模型的制作及宫内再通手术

对胎龄２．５～３个月的２０只绵羊胎仔制作小肠闭锁模型（正式实验１４只），同时对其中的５只实验胎仔实施宫内再通手术。模型成功率１０／１４，再通手术成功４只。对小肠闭锁模型中形成的粗大段的病理改变进行了讨论。     

外源性肺表面活性物质对宫内感染所致肺损伤胎兔肺组织白细胞介素-8表达的影响

目的探讨外源性肺表面活性物质(PS)对宫内感染所致肺损伤胎兔肺组织IL-8表达的影响。方法选取健康成年育龄日本大耳白兔19只,成功受孕后随机分为对照组、细菌组、细菌+PS组。建立宫内感染致肺损伤胎兔模型,对照组和细菌组按胎龄又分为21d、22d、23d、24d、26d5个亚组;细菌+PS组分为24d、26d2个亚组。细菌组宫内注射E.coli菌株,细菌+PS组宫内注射E.coli菌株,同时胎兔羊膜腔内注射PS200mg·kg-1,对照组宫内注射9g.L-1盐水。模型建成后分别在各时间点对孕兔行剖宫产,杀取胎兔后取肺组织,以鼠抗兔IL-8单克隆抗体为一抗,用免疫组织化学方法检测其肺组织内IL-8表达;用反转录-PCR检测其IL-8mRNA表达;用Westernblotting方法检测其IL-8蛋白表达;应用SPSS13.0软件进行统计学处理。结果细菌感染后胎兔肺组织IL-8mRNA、IL-8蛋白表达增高,与对照组比较差异有统计学意义(Pa=0.000)。免疫组织化学结果显示对照组支气管黏膜上皮细胞、平滑肌细胞、血管内皮细胞及巨噬细胞胞质内可见阳性表达,细菌组和细菌+PS组表达增强,在肺泡上皮细胞胞质也见明显表达...     

肛门直肠畸形大鼠胚胎后期肠管Cajal间质细胞的研究

目的 研究肛门直肠畸形(ARM)胎鼠胚胎后期16 d(E16)、21d(E21)小肠、结肠和直肠Cajal间质细胞(ICC)的发育情况.方法 体重250～300 g的wistar大鼠,雌雄鼠夜间合笼交配.早晨雌鼠阴道涂片,发现精子被认为是E0.孕鼠随机分成4组,E16对照组孕鼠2只、实验组孕鼠8只,E21对照组孕鼠2只、实验组孕鼠6只.胚胎第10天实验组孕鼠经胃管注入125 mg/kg的ETU,对照组孕鼠经胃管注入等量生理盐水.E16、E21孕鼠腹腔注射10%水合氯醛6 ml/kg,剖宫取出所有胎鼠,辨认胎鼠是否存在畸形及畸形类型.选取对照组胎鼠、实验组无畸形胎鼠和ARM胎鼠,在大体显微镜下解剖整个肠管.选取距盲肠8cm处小肠,距盲肠2咖处结肠,距肛门0.5 cm处直肠各一段.使用c-kit抗体通过SABC免疫组织化学方法研究E16和E2t对照组、实验组乙烯硫脲(ETU)诱导无畸形胎鼠、实验组ETU诱导ARM胎鼠小肠、结肠和直肠c-kit抗体表达情况.结果 E16对照组小肠、结肠、直肠肌间神经从周围可见中等量c-kit抗体染色阳性细胞,肌层部分细胞c-kit抗体染色阳性.E21对照组肌间神经丛周围c-kit抗体染色阳性细胞增多,可见阳性细胞网络形成.E16、E21实验组无畸形胎鼠小肠、结肠、直肠和实验组ARM胎鼠小肠与对照组相比,阳性细胞面积百分比、平均光密度值、积分光密度值和对照组相比,P>0.05,差异无统计学意义.而实验组ARM胎鼠结肠,直肠阳性细胞面积百分比、平均光密度值和积分光密度值明显减小P<0.05,差异有统计学意义.结论 ARM胎鼠胚胎后期小肠ICC发育正常而结肠、直肠ICC发育异常,这可能影响生后肠管ICC网络的形成和功能的发挥,可能是ARM术后便秘的病因之一.     

汉防己甲素对先天性膈疝大鼠的保护作用

目的：探讨汉防己甲素（TET）产前干预对先天性膈疝（CDH）大鼠的保护作用及机制。方法：将妊娠Sprague-Dawley大鼠随机分为对照组、除草醚组与TET治疗组。后两组孕 9.5 d 时采用除草醚灌胃法建立 CDH 大鼠模型;治疗组自孕18.5 d 起给予 TET 灌胃（每日30 mg/kg,连续3 d）;21 d 对部分孕鼠行剖腹并抽取羊水,观察胎鼠膈疝形成情况。采用 ELISA 法、免疫组化染色法检测羊水和胎肺中 TNF-α 的表达情况。余孕鼠自然分娩,观察各组仔鼠出生后情况。结果：除草醚组胎鼠无论有无膈疝形成均存在肺发育不良,肺及羊水中 TNF-α 的表达均明显升高;TET治疗组胎鼠巨大膈疝的发生率低于除草醚组,肺与羊水中 TNF-α的含量明显较除草醚组少（P＜0.01）。在自然分娩的仔鼠中,TET治疗组仔鼠的 24 h存活率明显高于除草醚组（P＜0.01）。结论：产前应用 TET 能降低CDH大鼠模型胎肺与羊水中 TNF-α 的含量,改善因除草醚诱导的胎鼠肺发育不良,减少巨大膈疝的发生,提高仔鼠的存活率。     

阿霉素诱导十二指肠闭锁的实验研究

目的 制作阿霉素诱导大白鼠胎仔出现先天性十二指肠闭锁的模型。方法 Ｗｉｓｔａｒ孕鼠１０只,于妊娠第６至第９天腹腔注射阿霉素１．７５ｍｇ／ｋｇ,妊娠２０天剖宫取胎仔,做解剖、电镜及光镜观察。结果 用药组获胎仔３２只,十二指肠闭锁２６例（８１．３％）,其中腔内闭锁１５．４％,闭锁近远端由纤维或胰腺相连者占４６．２％,近远端游离者为３８．５％,十二指肠闭锁畸形均伴有胰腺发育异常,９例胰颈、胰体及胰尾缺如     

叶酸缺乏孕鼠子代血细胞形态学改变及脑额区皮层超微结构表现

探讨叶酸缺乏对胎鼠宫内脑发育的影响、研究叶酸缺乏孕鼠子代胎鼠脑组织超微结构的改变及为叶酸缺乏造成脑发育障碍提供细胞水平的依据，及采用雌性SD大鼠实验组30只、对照组20只，分别饲以不含叶酸和含2mg叶酸/kg的纯合饲料，两周后与雄鼠交配，于怀孕第20天对孕鼠剖腹取胎，对模型进行评价并观察叶酸缺乏对胎鼠发育的影响，应用途射电镜观察胎鼠额区皮层超微结构的改变。结果显示：1．实验组孕鼠交配前及妊娠晚期末血清叶酸均明显低于对照组，外周血出现多分叶核粒细胞。实验组胎鼠血清叶酸也明显低于对照组，出现巨幼红细胞，RBC和HB均低于对照组，且伴有宫内生长限制。2．实验组胎鼠额区皮层超微结构观察示：神经元出现核切迹、局灶性核周腔扩张、异染色质减少、胞质内细胞器肿胀、核糖体减少；某些胶质细胞亦见类似改变；神经毡膜性结构不完整。结论：1．交配前两周开始限食叶酸直至妊娠期结束，所建立的叶酸缺乏孕鼠动物模型处于叶酸缺乏第三阶段，其胎鼠宫内生长限制，红细胞出现巨幼变，但没有产生神经管闭合的异常。这是较理想的妊娠中晚期叶酸缺乏的孕鼠动物模型。2．母体叶酸缺乏能造成胎鼠皮层脑组织超微结构的改变，可能导致神经无功能的紊乱和丧失，以致防碍脑结构和脑功能的正常发育。3．受孕前后增补叶酸宜延长至妊娠结束，以减少不良妊娠结局的危险。     

Evaluation of diluted amniotic fluid effects on histological changes of intestine of rabbit fetus with gastroschisis

Amniotic fluid exchange is a method for prevention of intestinal damage in gastroschisis, but its techniques are different in studies. We investigated the effects of amnioinfusion exchange on histological changes of intestine and feasibility and safety of amniotic fluid exchange through central vein catheter (CVC) placed in pregnant rabbit uterus. A total of 15 pregnant New Zealand white rabbits were selected. Fetuses were randomly divided into three groups (case, control, sham). On gestational day 25, under general anesthesia with midline laparotomy, the graved bicornuate uterus was exposed. In controls, fetus abdomen was opened by a transverse incision in right lower quadrant region and intestines were eviscerated. In cases, after intestine evisceration, a central venous catheter was passed from mother skin and uterus and fixed to uterus wall. In shams, fetus was delivered on gestational day 32 and its abdomen was opened. In case group, after operation, 1–2 cc of warm saline solution was replaced through catheter every 6 h. On gestational day 32, fetuses of case and control groups were delivered. Mucosal and serosal thickness, muscle thickness, fibrin deposition, serosal collagen and ganglia were compared. Ten fetuses as shams, 7 fetuses as controls and 7 fetuses as case group were studied. Serosal thickness was 4.5 ± 3.6 μm in shams, 64.2 ± 28.7 μm in controls and 6 ± 4.1 μm in cases. Serosal thickness in control group was higher than sham (P < 0.001) and case (P < 0.002) groups. In case group, infiltration of inflammatory cells with mild edema without fibroblast infiltration was seen. Application of the CVC technique was found to be a simple procedure that effectively decreased serosal inflammatory response of intestine in gastroschisis.     

The impact of iatrogenic gastroschisis on pulmonary maturation in the fetal rabbit models of congenital diaphragmatic hernia

Purpose  The aim of this study was to analyze the effect of iatrogenic gastroschisis on pulmonary hypoplasia in fetal rabbits with congenital diaphragmatic hernia (CDH). Materials and methods  A total of 30 pregnant rabbits received fetal surgery on gestational day 23. A left diaphragmatic hernia was created in one end fetus (DH group) of each rabbit, and the other end fetus of the same rabbit received sham thoracotomy as control (CR group). Another 19 pregnant rabbits underwent partial resection of the diaphragm in both end fetuses on gestational day 23, and then artificial gastroschisis was performed on one end fetus (GS group) on gestational day 26, while the other end remained as control (CGS group). The fetuses were harvested on gestational day 30. The histological and morphometric evaluation of lungs and livers of the end fetuses in each group was conducted. Results  In the DH group, the lungs were hypoplastic with a decrease in the total lung weight to body weight ratio, and remarkable thickening in alveolar septa. The lung vessels showed significantly thicker arterial walls when compared with those from control fetuses. The pathological finding in the CGS group was similar to that of the DH group. The thickness of the alveolar septa and of the pulmonary arterial walls showed no significant difference among the GS group, DH group and the CGS group. The ratio of liver weight to body weight increased notably in the GS group, DH group and CGS group compared with that in the CR group. Conclusions  In the fetal rabbit models of CDH, pulmonary hypoplasia is the most significant pathological feature. Iatrogenic gastroschisis does not improve pulmonary maturation due to the active growth of the liver that herniates into the thoracic cavity.     

The effect on the intestines of continuous release of methylene blue from a drug delivery system: an experimental study in a chick embryo gastroschisis model

Increased small bowel nitric oxide synthase (NOS) activity has been suspected as a cause of postnatal intestinal dysmotility in gastroschisis. The effect of continuous delivery of methylene blue loaded polymer (MBLP) hydroxy-propyl methyl cellulose-ethyl cellulose (HPEC—MC) and daily injection of methylene blue (MB) on the intestinal damage (ID) was evaluated using a chick embryo gastroschisis model. Fourteen-day-old fertilized chick eggs were divided into five groups. In the control (C) group, no intervention was performed. In the sham (S) group, the allantoic and amniotic membranes were opened to create a common cavity that resembles the amniotic cavity in human. In the gastroschisis only (GO) group, a defect in the abdominal wall of the embryo was made, and intestinal loops were exteriorized following connection of amniotic and allantoic cavities. In the gastroschisis plus methylene blue (G+MB) group, gastroschisis was created and MB administered into the amnioallantoic cavity (AAC) by daily injections for 5 days. In the gastroschisis plus methylene blue loaded polymer (G+MBLP) group, MBLP was placed into AAC after gastroschisis was created. At the end of the 19th day of incubation, intestinal morphological changes were investigated macroscopically and microscopically. Although the survival rates were decreased in the chick embryos with creation of gastroschisis compared with C and S groups (p<0.001), the survival rates were increased in G+MBLP group (76.92%) when compared with the GO group (41%) (p<0.001). Because of multiple intervention of embryos, higher mortality was observed in the G-MB group (75.61%). Macroscopic and microscopic scores of ID and mean intestinal wall thickness were significantly higher in the GO group when compared with C, S, G+MB, and G+MBLP groups (p<0.001). The mean score of intestinal ganglia morphology was significantly increased and the total number of ganglion cells was significantly decreased in the GO group when compared with C, S, G+MB, and G+MBLP groups (p<0.001). It is possible to decrease intrauterine intestinal morphological changes in gastroschisis by inhibiting NOS. As a first preliminary study, we believe that use of MBLP may be an alternative for fetal treatment by eliminating the harmful effects of multiple interventions or amniotic fluid exchanges.     

The development of the gastrointestinal system in fetal sheep in the absence of ingested fluid

Our aim was to determine the effects of preventing the passage of ingested fluid on the development of the digestive tract in fetal sheep. The esophagus was fistulated and ligated in six fetuses at 90 days of gestation (term = 145 days); vascular catheters were implanted at day 120. Six control fetuses had vascular catheters implanted at day 120. At autopsy (day 135), although fetal body weights were similar in both groups, the abdominal girth and weights of the gastrointestinal tract, liver, and pancreas were reduced in experimental fetuses. In the gastric (abomasal) fundus and antrum, there was evidence of altered mucus composition in epithelial cells, a decrease in thickness of the muscularis externa, and an increase in thickness of the mucosa and its components. In the duodenum, there were significant changes in the thickness of most components of the wall; Brunner's glands were greatly reduced in size of were absent. Glandular cells contained less mucus in comparison to controls. In the proximal small intestine, there were significant reductions in the thickness of most components of the wall, and epithelial cell migration was retarded, resulting in a longer renewal time for villous cells. In the distal small intestine, the diameter of the intestine and submucosal and epithelial cell migration rate were significantly decreased in the experimental group. In summary, the absence of the passage of ingested fluid in fetal sheep restricts the growth and development of the gastrointestinal tract, liver, and pancreas.     

Is induction of fetal diuresis with intraamniotic furosemide effective for the removal of intestinal waste products from amniotic fluid?

AIM: In gastroschisis, contact with amniotic fluid (AF) causes intestinal damage. Intraamniotic meconium has been shown to be responsible for the intestinal damage, and intestinal damage has been shown to correlate with intraamniotic meconium concentrations. Intraamniotic meconium below a threshold level does not cause intestinal damage. Intraamniotic meconium concentrations can be lowered by AF exchange. Can induction of foetal diuresis by an intraamniotic injection of furosemide be used as an alternative method for the same purpose? METHOD: Pregnant rabbits on the 23rd - 25th gestational days (normal gestation time: 31 - 33 days) were divided into two groups, the control group and the furosemide group. Initial AF samples were taken, then either 5 mg/kg furosemide or a placebo was injected into the amniotic cavity. Final AF samples were obtained 6 hours later. AF urea nitrogen, creatinine, amylase, alkaline phosphatase and bilirubin levels were determined. RESULTS: There was no significant difference between the initial and final levels of AF urea nitrogen, creatinine, bilirubin, amylase, and alkaline phosphatase in the control group, while the final AF urea nitrogen and creatinine levels of the furosemide group were not significantly different from the initial levels (p > 0.05). Final AF bilirubin, amylase and alkaline phosphatase levels of the furosemide group were significantly decreased compared with initial levels (p < 0.01). CONCLUSION: Induction of foetal diuresis with intraamniotic furosemide is effective for the removal of intestinal waste products from amniotic fluid.     

Fetal redistribution of blood flow and amniotic fluid volume in growth-retarded fetuses

Our purpose was to assess the relationship between the fetal redistribution of blood flow and the amount of amniotic fluid in appropriate-for gestational-age fetuses and growth-retarded fetuses. Blood flow velocity waveforms of the umbilical artery, descending aorta, middle cerebral artery, renal artery and uterine artery were recorded using pulsed Doppler ultrasonography in 100 appropriate-for gestational age fetuses and 39 growth-retarded fetuses. The pulsatility index (PI) values and the amount of amniotic fluid were compared between the two groups. The PI values of the umbilical artery and renal artery were significantly higher in appropriate for gestational-age-fetuses with oligohydramnios than in fetuses with an adequate amount of amniotic fluid. The PI values of the umbilical artery and renal artery were significantly higher and the PI of the middle cerebral artery was significantly lower in growth-retarded fetuses with oligohydramnios than in fetuses with an adequate amount of amniotic fluid. Furthermore, there was a significant negative correlation between the PI value of the renal artery and the vertical diameter of amniotic fluid, and between the PI value of the renal artery and the amniotic fluid index. The PI value of the renal artery was related to the amount of amniotic fluid in growth-retarded fetuses, and the same relationship was demonstrated in appropriate-for gestational age fetuses.     

Intra-amniotic endotoxin accelerates lung maturation in fetal rabbits

The hypothesis that endotoxin in amniotic fluid accelerates fetal lung maturation was tested. On day 25 of gestation, LPS (5 microg/fetus) was injected intra-amniotically into one uterine horn of eight New Zealand white rabbits, whereas the contralateral amniotic sacs were injected with saline vehicle. The fetuses were delivered 48 h after LPS administration and their lungs were studied. One dam went into premature labor prior to the 48 h time point and was excluded from the study. Mean white cell counts in amniotic fluid and bronchoalveolar lavage fluid from LPS-treated fetuses were increased 3.2-fold (p = 0.04) and 9.9-fold (p = 0.04), respectively. Fetal weights and lung weights were not affected by LPS. Surfactant protein SP-A and SP-B mRNA expressions in LPS-treated fetuses were increased 2.3-fold (p = 0.03) and 1.4-fold (p = 0.04), respectively. Static lung compliance was increased in animals treated with LPS (p = 0.001). Lungs from LPS-treated animals had better aeration than those of controls. Mean volume of inflation-fixed lungs of LPS-treated fetuses was 1.7 times greater than that of controls (p = 0.03). CONCLUSION: Intra-uterine exposure to LPS increases surfactant protein expression and improves lung stability and aeration in preterm animals.     

Prenatal developmental toxicity studies of 1,1,1-trichloro-2,2-bis(4-methoxyphenyl)ethane (methoxychlor) in rats and rabbits

ABSTRACT  The studies were conducted in rats and rabbits to elucidate the potential developmental toxicity of methoxychlor in general accordance with the improved Japanese MAFF guidelines (12-Nousan-No. 8147, 2–1–18, 2000). Methoxychlor dissolved in corn oil was administered orally to pregnant Jcl:SD rats on gestational days (GD) 6–19 at a dose of 0,1,50, or 150 mg/kg/day and to pregnant Kbl:JW rabbits on GD 6–27 at a dose of 0,1, 15, or 45 mg/kg/day. Maternal animals were killed on the day after the last day of administration for morphological examination of their fetuses with special attention to the reproductive organs.
Adverse effects on maternal animals were found at 2 higher doses in both species; i.e. vaginal red discharge (rat only), abortion or premature delivery (rabbit only), and significantly decreased body weight gains and food consumption. While the numbers of corpora lutea and implants were comparable between the control and treated groups in both species, slight increase in the percent resorptions and fetal deaths in rats and a reduction of fetal weights in both species were observed at the highest dose. Anogenital distance and testicular histology were not affected in rats. Although fetal examination revealed significant increase in the incidences of 27 presacral vertebrae at 2 higher doses in rabbits, there was no treatment-related increase in the incidence of malformations in rats and rabbits.
Based on these results, it is concluded that methoxychlor causes no malformations, including male reproductive organ abnormalities, in either rats or rabbits, although it results in decreased fetal weights and an increased incidence of fetal resorptions or skeletal variations at maternally toxic doses.     

Effect of epidermal growth factor on lung growth in experimental fetal pulmonary hypoplasia

The purpose of this study was (1) to compare the expression of epithelial growth factor receptor (EGFR) in the lung tissues of human fetuses with or without pulmonary hypoplasia, and (2) to investigate the effects of EGF on lung growth in experimental pulmonary hypoplasia in rabbits. Firstly, we investigated the expression of EGFR in lung tissues of human fetuses with or without pulmonary hypoplasia by immunohistochemistry. Secondly, the amniotic fluid was shunted into the maternal abdominal cavity in a group of 12 fetal rabbits, another group (n = 12) received EGF injection (5 microg, i.p.) at day 25 of gestation. The third group (n = 12) was only treated with EGF while littermates not operated on served as the control group (n = 12). On day 29 of gestation, fetuses were delivered by Cesarean section and the lungs removed. The body weight and wet lung and liver weights were measured. As a measure of fetal lung growth, we determined the size of lung acini, the number of terminal airspaces, and diameter of alveoli (n = 6, each groups). We also measured the concentration of phosphatidylcholine (PC) and the lecithin/sphingomyelin (L/S) ratio in lung lavage fluid at birth in some fetuses (n = 6, each groups). In human fetuses with pulmonary hypoplasia, there was a significant decrease in radial alveolar count and expression of EGFR compared with fetuses without pulmonary hypoplasia. Amniotic shunt significantly decreased fetal lung/body weight ratio compared with control. Injection of EGF in the shunted group significantly increased lung/body weight ratio to the control level. The concentration of PC and L/S ratio in lung fluid lavage from rabbit fetuses with hypoplastic lungs was significantly higher than the other three groups. Histopathological examination of fetuses with hypoplastic lungs treated with EGF showed no significant change in the size of acini, number of terminal airspaces or the diameter of alveoli compared with the control group. Our results suggested that EGF was associated with lung growth and maturation of human lung and that treatment of rabbit fetuses with hypoplastic lungs with EGF facilitated lung growth and development.     

Prenatal developmental toxicity studies of 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p, p'-DDT) in rats and rabbits

ABSTRACT  The studies were conducted in rats and rabbits to elucidate the potential developmental toxicity of p, p '-DDT in general accordance with the improved Japanese MAFF guidelines (12-Nousan-No. 8147,2–1–18, 2000). p, p '-DDT suspended in 1% aqueous solution of CMC was administered orally to pregnant Jcl:SD rats on gestational days (GD) 6–19 at a dose of 0,5, 25, or 100 mg/kg/day and to pregnant KbI: JW rabbits on GD 6–27 at a dose of 0,5,20, or 80 mg/kg/day. Maternal animals were killed on the day after the last day of administration for morphological examination of their fetuses with special attention to the reproductive organs.
Adverse effects on maternal animals were found only at the highest dose in both species; i.e. , clonic convulsion (2/24 in rats, 5/22 in rabbits), mortality (1/24 in rats), abortion or premature delivery (4/22 in rabbits), and reduced body weight gains and food consumption. However, the control and treated groups showed comparable values for the numbers of corpora lutea and implants, percent preimplantation losses, number of live fetuses, percent resorptions and fetal deaths, sex ratio, fetal body weights, and placental weights in both species, and anogenital distance and testicular histology in rats. Although fetal examination revealed slightly increased incidence of 27 presacral vertebrae in the highest dose group in rats, there was no treatment-related increase in the incidence of malformations in any of the species.
Based on these results, it is concluded that p, p '-DDT causes no malformations, including male reproductive organ abnormalities, in either rats or rabbits, although it results in an increased incidence of skeletal variations in rats at a maternally toxic dose.