[Observations on normal histology of umbilical vessels in various months of intrauterine fetal development].
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We have determined expression of human GGT gene encoding gamma-glutamyl transpeptidase (GGT) during fetal development of liver using the Northern-blot analysis with a cloned human GGT cDNA and immunohistochemistry with a monoclonal antibody. GGT mRNA could be detected as early as the 12th week of gestation. It then increased gradually to a peak of approx. threefold the amount at week 12, at week 40, just before birth. The size of the mRNA in the fetal liver was 2.7 kb and mRNA of the same size was detected both in the human fetal kidney and human hepatocellular carcinoma as well as normal adult liver. Immunohistochemical analyses show that GGT increased as the fetal liver developed in parallel with the increase in mRNA. Histochemically, GGT was shown to be located in the wall of bile canaliculi when synthesis was low in early development, but to be distributed, in addition, all over the cell membrane of the fetal hepatocytes when synthesis was high at the later stage of development.
To examine the effects of simulated weightlessness on cortico-adrenal function and on fetal development, we suspended pregnant rats for 20 days. The levels of adrenal and plasma corticosterone were examined in mothers and in fetuses. The animal control group was kept single in standard cages. Growth of the suspended animals was repressed for the first 8 days of the experiment, but thereafter it increased greatly, as did the daily food intake. By the 18th day of the experiment, the body masses and food intake of the two groups were equal. No modification in circulating corticosterone was found. It appears that there is no stress in pregnant rats submitted to simulated weightlessness.
We have identified the first TCRs to be generated in vivo during normal human fetal development. Before thymic formation, the liver is a site of generation for a subset of V gamma 9/V delta 2+ gamma delta T cells. Analysis of the expression of the male-specific gene, SRY, by V gamma 9/V delta 2+ gamma delta T cells isolated from the fetal liver of male donors has shown that these cells are generated de novo in the liver. Examination of TCR-V gamma and -V delta gene expression demonstrated that although multiple receptor rearrangements could be detected, V gamma 9-JP- and V delta 2-D delta 3-J delta 1/3-encoded receptors were preferentially expressed in each of five individual liver samples. Structural analysis of these receptor chains and those expressed by a panel of V gamma 9/V delta 2+ fetal T cell clones showed that the V gamma 9-JP receptors were invariant or canonical and that the delta-chains contained non-germ line-encoded structural motifs. gamma delta T cells expressing these structurally limited receptor chains were shown to be functional and capable of responding to mycobacterial Ags. Together with the observation that V gamma 9/V delta 2+ cells represented the majority of T cells present in the fetal liver between 7 and 11 wk of development, our findings demonstrate that this subset of gamma delta T cells is a major, and presumably important, component of the human fetal immune system.
OBJECTIVE: To study the fetal developmental regulation and gestational weeks at labor for triplets pregnancies. METHODS: To detect biparietal diameters and femoral length at different gestational weeks, record gestational weeks of labor and birth weights, and compare with those of singletons. RESULTS: The fetal development of triplets slowed down from the beginning of the 28th gestational week compared with that of singletons (the mean difference was 2.1 mm and 3.1 mm respectively, P < 0.01, P < 0.01). Birth weights of 36.2% triplets was less than that of the 10th percent of the same singletons gestational week. 95.7% triplets delivered their babies before 36 weeks. The average gestational week was 34.0 +/- 1.6, obviously ahead of the singletons'. CONCLUSION: The fetal developmental regulation of triplets pregnancies is different from that of singletons, the gestational period is shorter than those of twins and singletons.
The objective of this study was to assess the response of the feline thymus to fetal infection with feline immunodeficiency virus (FIV), an animal model for human immunodeficiency virus infection. Thirteen feline embryos from four litters were directly inoculated with FIV during the sixth week postbreeding, a period corresponding to the late second trimester of pregnancy. Thymus tissue was collected and analyzed from randomly selected kittens at 2, 4, and 16 weeks postinoculation (PI) and compared to age-matched control kittens that did not receive fetal inoculations. Of three kittens evaluated at 2 weeks PI (week 8 of gestation), neither thymus:body weight ratio nor histologic structure differed from five age-matched control animals. However, analysis of thymocyte subpopulations by flow cytometry revealed a significant (P = 0.011) reduction in the percentage of cluster of differentiation (CD)4+/CD8+ cells from an average of 66% in control fetuses to 45% in infected fetuses. FIV RNA transcription, assessed by in situ hybridization using an FIVgag RNA probe, was widely distributed throughout the thymus in patterns suggestive of both stromal and parenchymal infection. By 4 weeks PI (week 1 postpartum), the thymus:body weight ratio was significantly reduced (P = 0.007) from 0.36% in five control kittens to 0.13% in four fetal inoculates. Severely atrophied thymus lobules supported minimal virus transcription and mean CD4+/CD8+ thymocyte percentages were lower (P = 0.021) in infected kittens (15%) compared to age-matched controls (66%). By 16 weeks PI (week 12 postpartum), thymus:body weight ratios of six inoculated kittens were not significantly different from six age-matched controls, suggesting that partial postnatal thymus regeneration had occurred. However, despite similar size, the regenerative thymus contained reduced percentages of CD4+/CD8+ thymocytes (infected: 40% versus control: 76%; P = 0.009) and increased percentages of CD4+/CD8- (11% versus 5%; P = 0.002) and CD4-/CD8+ (16% versus 9%; P = 0.035) lymphocytes. These changes were associated with widespread FIV transcription within thymic lymphocytes. Thus, the thymus of kittens infected with FIV during late fetal development is characterized by two distinct changes: neonatal atrophy and postnatal regeneration. Despite a recovery in thymus weight, thymus regeneration ineffectively restores the normal phenotypic distribution of thymocytes and supports FIV transcription.
To assess the potential effect of cyclopiazonic acid (CPA) on pregnancy and fetal development, Fischer-344 rats were dosed daily with 0, 1, 5, or 10 mg CPA/kg body weight on either d 8-11 or d 12-15 of pregnancy (sperm day = d 1). There were significant (p less than 0.05) decreases in feed consumption by high-dose dams of both groups. One high-dose rat in each group died prior to term, and signs of toxicity were observed in other high-dose animals. Animals that died had histologic lesions in the liver, spleen, kidney, and other organs. Remaining dams were killed on d 21. Compared to controls, there were no significant differences in pup weights, percentage pre- or postimplantation losses, or fetal deaths. Significant differences in skeletal development included retardation of ossification of cervical centra (d 12-15) and caudal vertebrae (d 8-11) in the two highest dose groups. Retardations of development were the most common manifestations of embryotoxicity. Since significant maternal toxicity occurred at the highest dose level in the absence of fetal malformations, the teratogenic potential of CPA is low.
The application of targeted gene inactivation methodologies to the study of late fetal development and control of the timing for parturition in mice has yielded insight into the mechanisms that enhance fetal survival. An essential role for glucocorticoids in promoting lung maturation sufficient for viability ex utero before the onset of normal parturition has been demonstrated in corticotropin-releasing hormone-deficient mice. In contrast, maternal deficiency in the prostaglandin synthetic enzyme cyclooxygenase-1 results in the markedly delayed onset of labor and fetal demise because of postdates gestation. The complex interplay of factors that govern the onset of labor is highlighted by mice deficient in both cyclooxygenase-1 and oxytocin. Whereas mice deficient in oxytocin demonstrate normal parturition, simultaneous cyclooxygenase-1 and oxytocin deficiency rescues the delayed onset of labor found in cyclooxygenase-1 knockout mice but results in the prolonged duration of labor. The consequences of complete deficiency of molecules involved in parturition in mice suggest novel interventions for human preterm labor.
Effects of heavy, moderate, and rare alcohol consumption on fetal development were analyzed in a prospective study of 469 mother-infant pairs. Differential effects of heavy drinking in early and late gestation were evaluated by separate analysis of neonates born to women who reduced consumption before the third trimester. Using chi 2 analysis, multiple regression, and matched sets, statistically significant associations (P less than .01) were observed between sustained heavy drinking and both intrauterine growth retardation and congenital anomalies. These associations were independent of eight other risk factors. No differences were observed between offspring of rare and moderate drinkers. Infants born to women who reduced heavy drinking did not differ in growth from offspring of rare and moderate drinkers but demonstrated a higher frequency of abnormalities. Sustained heavy drinking represents a major risk; reduction in midpregnancy can benefit the newborn. Identification and therapy of heavy drinking are important components of prenatal care.
The aim of this work was to determine the pattern of expression of hepatic bilirubin UDP-glucuronosyltransferase throughout fetal development in rats, with the purpose of using fetal hepatocytes at the most appropiate stage of development for transplantation into Gunn rats lacking bilirubin UDP-glucuronosyltransferase activity and then assessing the therapeutic capacity of the implants. The results show that at day 13 of gestational life there is already bilirubin UDP-glucuronosyltransferase gene expression. Twenty-one-day fetal hepatocyte transplantation was also performed into the spleens of hyperbilirubinemic Gunn rats, when alpha-fetoprotein mRNA is still detectable. At 15, 30, and 90 days after transplantation, a mild decrease in total bilirubin serum levels was observed. An increase in bile conjugated bilirubin also was observed at 30 and 90 days. These data suggest the favorable evolution of transplanted cells and show its feasibility for therapy.
In this study, maternal toxicity and developmental effects of exposure to Ascaris trypsin inhibitor were evaluated in mice. Pregnant BALB/c females were injected intraperitoneally by Ascaris inhibitor /AIT/ at 200, 300, and 400 mg/kg body weight/day, on days 12 to 15 of gestation (stage of fetal development). At day 19 of pregnancy, uterine contents were inspected for implantation sites, early resorptions (moles), living fetuses and dead fetuses. The living fetuses were weighed and examined for external, internal and skeletal abnormalities. The results showed that AIT induced maternal toxicity, evidenced by maternal deaths, abortions, bleeding from uterus and reduced body weight gain as compared to control (p < 0.01). There were no differences between the control group and the rest of all groups investigated for total implantation sites and early resorptions. Fetotoxicity was observed as shown by the decrease in the number of living fetuses and mean fetal weight, a high rate of intrauterine fetal deaths, delayed skeletal ossification, occurrence of pathological changes of fetal organs and tissues. Only one type of congenital malformations (hydronephrosis) was noted in fetuses after injection of higher doses of AIT.
A surfactant NP-10 was administered subcutaneously to 7-week-old Jcl:Wistar female rats at dose levels of 2 and 20 mg/kg/day for 15 weeks to assess its effects on their reproductive ability and fetal development, and on the growth, behavior and functions of the offspring they delivered. In the general condition of the F0 dams, changes that were considered to be the local irritation effect of the test substance, such as scab formation and loss of hair at the test substance administration site in the 2 and 20 mg/kg groups and induration of the skin at the test substance administration site in the 20 mg/kg group were observed. Whitish changes of the subcutis were detected at the test substance administration site in the 2 and 20 mg/kg groups and adhesion of abdominal organs in the 20 mg/kg group in the necropsy findings. In addition, an increase was observed in body weight and in food consumption in the 20 mg/kg group. The reproductive ability test failed to reveal any evidence of an effect that could be ascribed to the test substance. The observations at cesarean section or external, visceral and skeletal examinations revealed no effects attributable to the test substance in the F1 fetuses. The observations on the day of birth and during the period of lactation, external examination, physical development test, general condition, body weight and necropsy findings for F1 and F2 offspring and reflex test, open-field test, water-maze test, organ weight and reproductive ability test performed on the F1 offspring failed to reveal any evidence that could be ascribed to the test substance. These results indicate that under the conditions of this study, NP-10 had no effect on the reproductive ability of females or the fetal development or growth, behavior and functions of their offspring.
Fetuses from hamsters exposed to repetitive 5.2-ATA (140 fsw) air dives during early pregnancy showed no significant differences from the control group in birth weight, frequency of malformation, or death. Also, exposure of mothers to hyperbaric oxygen as required for treatment of decompression sickness (DCS) has no adverse effect on fetal development or survival. Although the number of females who suffered and survived DCS in this study was small (n = 3), teratogenic effects were nevertheless found among the fetuses of this group. In fact, at least one fetus from each female undergoing DCS was found to have serious malformations. These results suggest that DCS during early organogenesis may have significant deleterious effects on fetal development.
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The authors determined gestational age from fetal weight, examined the range in conception dates, and classified the external fetal development process in sika deer of eastern Hokkaido. Gestational age (T) can be estimated from fetal weight (W) with the equation: T = (3 square root of W + 2.730)/0.091. Conception date can then be calculated back from date of kill of pregnant female, using gestational age. Though estimated conception dates ranged from 7 October to 17 January, most of them were concentrated between mid October and early November. In late November and after, nine conceptions were observed and six out of the nine late cases occurred in yearling females. This phenomenon is probably due to the excellent nutritional condition of deer in the study areas, which allows yearling females to mature sexually even in early winter. In fetuses, periods of tactile hair development, appearance of white spots, and development of general hairs overlap very little. In addition, these developmental changes occur at specific fetal weights. Based on these external phases, the gestation period can be divided into four stages. These stages will be useful for simple determination of fetal age in various sika deer populations.
Oral vanadate treatment is effective in normalizing blood glucose in both Type I and Type II diabetics. Using Sprague Dawley rats we examined the effectiveness of such treatment in amelioration of hyperglycemia in diabetic pregnancy and its effect on fetal growth in both normal and diabetic pregnant dams. Initiation of vanadate treatment to diabetic and normal pregnant dams increased blood vanadium levels in both groups, but this concentration in the diabetic pregnant group reached approximately twice the value present in the normal group. Despite this high blood vanadium level in the diabetic pregnant dams, oral vanadate treatment was not effective in normalizing blood sugar in this group. Additionally, vanadate treatment was found to be toxic during diabetic pregnancy, causing death to 45% of the test animals. Maternal blood vanadium had a negative effect on fetal development, markedly reducing the number of live fetuses per pregnancy. In summary, oral vanadate treatment is toxic and ineffective during diabetic pregnancies and interferes with fetal growth and development in both normal and diabetic pregnancy.
BACKGROUND: Given the role of nutrition and body weight gain in normal development, pharmaceuticals intended to reduce appetite and promote weight loss will generate safety data that may be challenging to interpret. To aid with this, the effects of feed restriction and subsequent body weight reductions on embryo-fetal development were investigated in the rat. METHODS: Groups of 20 timed pregnant female Sprague-Dawley rats were offered Certified Rodent Diet 5002 either ad libitum or in restricted amounts of 20, 15, 10, and 7.5 g/day from Gestation Day (GD) 6-17. Clinical signs, body weights, and food consumption were recorded. Cesarean sections were performed on GD 21 and fetuses were sexed, weighed, and examined for external, visceral, and skeletal development. RESULTS: Mean maternal body weights at the end of the feed restriction period, GD 18, were reduced 0.87 x, 0.80 x, 0.69 x, and 0.63 x control mean in the 20, 15, 10, and 7.5 g/day groups, respectively. Mean body weight gains for the restriction period inclusive, GD 6-18, were 0.49 x and 0.24 x control at 10 and 7.5 g/day, respectively, and a mean body weight loss occurred at 10 and 7.5 g/day (0.95 x and 0.85 x mean GD 6 body weight, respectively). Fetal body weights were reduced 0.95 x, 0.93 x, 0.90 x, and 0.76 x control at 20, 15, 10, and 7.5 g/day, respectively. This resulted in a reduction in gravid uterine weight at 10 and 7.5 g/day. There were no external, visceral, or skeletal malformations attributed to feed restriction. There was an increase in the skeletal variation of wavy ribs and a decrease in ossification at 7.5 g/day. CONCLUSIONS: These data demonstrate that feed restriction-induced reductions in maternal gestational body weight gain of approximately 50% compared to ab lib fed rats only caused a reduction in fetal body weight. Even up to a 15% maternal gestational body weight loss had no effect on embryo viability in rats, but retarded fetal growth significantly enough to induce minor changes in skeletal development. There were no external, visceral, or skeletal malformations associated with any of the levels of maternal body weight reduction or loss.