Administration of growth hormone or IGF-I to pregnant rats on a reduced diet throughout pregnancy does not prevent fetal intrauterine growth retardation and elevated blood pressure in adult offspring.
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Increasing evidence from human epidemiological studies suggests that poor growth before birth is associated with postnatal growth retardation and the development of cardiovascular disease in adulthood. We have shown previously that nutritional deprivation in the pregnant rat leads to intrauterine growth retardation (IUGR), postnatal growth failure, changes in the endocrine parameters of the somatotrophic axis, and to increased blood pressure in later life. In the present study, we investigated whether administration of insulin-like growth factor-I (IGF-I) or bovine growth hormone (GH) during pregnancy could prevent IUGR and/or alter long-term outcome. Dams from day 1 of pregnancy throughout gestation received a diet of ad libitum available food or a restricted dietary intake of 30% of ad libitum fed dams. From day 10 of gestation, dams were treated for 10 days with three times daily subcutaneous injections of saline (100 microl), IGF-I (2 micrograms/g body weight) or GH (2 micrograms/g body weight). Maternal weight gain was significantly increased (P<0.001) in ad libitum fed dams treated with GH, (98.9+/-4.73 g) compared with the IGF-I (80.5+/-2.17 g) and saline-treated (70.7+/-2.65 g) groups. There was a small increase in maternal weight gain (P<0.06) in 30% ad libitum fed dams following GH (16.3+/-2.47 g) and IGF-I (15.8+/-1.97 g) treatment compared with saline (9.2+/-1.96 g). Whole spleen, kidney and carcass weights were significantly (P<0.05) increased in ad libitum fed and 30% ad libitum fed dams with GH treatment. Circulating IGF-I was significantly increased (P<0.001) in ad libitum fed dams with both IGF-I (369.6+/-32.33 ng/ml) and GH (457.9+/-33.32 ng/ml) compared with saline treatment (211.7+/-14.02 ng/ml), and with GH (223.4+/-23.72 ng/ml) compared with saline treatment (112.0+/-7.33 ng/ml) in 30% ad libitum fed dams. Circulating GH binding protein (GHBP) levels were significantly reduced (P<0.05) in GH-treated (299.1+/-51.54 ng/ml) compared with saline-treated (503.9+/-62.43 ng/ml) ad libitum fed dams, but were not altered in 30% ad libitum fed dams. There was no significant effect of either IGF-I or GH treatment on fetal weight, placental weight, fetal organ weights or circulating IGF-I levels in both ad libitum fed and 30% ad libitum fed fetuses. Offspring of 30% ad libitum fed dams remained significantly growth retarded postnatally and showed elevated blood pressure in later life. The increased maternal weight gain following IGF-I or GH administration, without an effect on fetal and placental weights, suggests a modification in the mode of maternal nutrient repartitioning during mid to late pregnancy at the expense of the fetus. (+info)
Abundance of leptin mRNA in fetal adipose tissue is related to fetal body weight.
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Leptin mRNA was measured in adipose tissue of fetal sheep by reverse transcription polymerase chain reaction (RTPCR). Abundance of leptin mRNA relative to b-actin mRNA in fetal perirenal adipose tissue increased (P<0.02) with gestation, being higher at 144 d (0.73 +/- 0. 10, n=5) than at 90-91 d (0.40 +/- 0.08, n=6) or 125 d (0.40 +/- 0. 04, n=5) gestation (term approximately 147- 150 d). There was a positive relationship between relative abundance of leptin mRNA (y) and fetal body weight (x)between 90 and 144 d gestation (r 2 =0.27, P<0.01). The slope of the linear dependence of leptin mRNA on fetal weight was 15-fold greater (P<0.001) at 90-91d (y = 2.81x - 1.1, n=6, r 2 =0.71, P<0.025) than between 125-144 d gestation (y = 0.195x - 0.15, n=16, r 2 =0.39, P<0.01). Thus the leptin synthetic capacity of fetal adipose tissue appears to increase in late gestation but this is accompanied by constraint of its sensitivity to fetal body weight. We hypothesise that leptin synthesis in fetal adipose tissue is related to fetal nutrient supply and growth rate. (+info)
Adaptation of pancreatic islet B-cells during the last third of pregnancy: regulation of B-cell function and proliferation by lactogenic hormones in rats.
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In rodents, placental lactogen (PL)-I is considered to be the first trigger to enhance pancreatic islet B-cell function, and after its secretion is diminished at mid-pregnancy, PL-II takes over this role. However, little information is available on the regulation of islet B-cell function and proliferation by lactogenic hormones during the last third of pregnancy. This was the focus of the present study using rats in which pregnancy was forcibly prolonged. This rat possesses unique characteristics in that PL-I is re-secreted during the prolonged period of pregnancy and the peak concentrations in maternal circulation are comparable with those observed during mid-pregnancy in normal-pregnancy rats. Pregnancy was prolonged by successive administration of pregnant mare's serum gonadotropin (30IU/rat, s.c. on day 12) and human chorionic gonadotropin (10IU/rat, i.v. on day 14). When the insulin secretory responses to 10mmol/l glucose in islets obtained from normal-pregnancy and prolonged-pregnancy rats were tested, each insulin secretory response correlated well with the values of plasma lactogenic activity throughout the period of pregnancy and lactation. Examination of B-cell proliferation in normal-pregnancy rats showed that 5-bromo-2'-deoxyuridine (BrdU) incorporation into dividing B-cells reached a maximum on day 15 and then decreased markedly towards term. No increase in B-cell proliferation was observed on day 19 when plasma lactogenic activity reached the maximum. In prolonged-pregnancy rats, BrdU incorporation also continued to decrease as observed in normal-pregnancy rats after day 15, and then no enhancement in B-cell proliferation was observed even when the plasma lactogenic activity, including re-secreted PL-I, reached maximum. These results suggest that, in the last third of pregnancy, B-cell proliferation is no longer stimulated by lactogenic hormones in contrast to the insulin secretory response which is sustained. (+info)
Protective effects of garlic juice against embryotoxicity of methylmercuric chloride administered to pregnant Fischer 344 rats.
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In order to investigate the beneficial effects of 0.5 or 1.0 g/kg Korean garlic juice against the embryotoxicity of 20 mg/kg methylmercury chloride (MMC, CH3HgCl), pregnant Fisher 344 rats were simultaneously orally administered on day 7 of gestation. On day 20 of gestation the dams were laparotomized under ether anesthesia, and the fetuses were removed and examined for toxicity of methylmercury. Garlic juice depressed the toxicity in terms of some parameters. In the case of simultaneous treatment with 0.1 g/kg garlic juice and MMC, rates of increase were 17.5% in maternal body weight, 13.2% and 41.9% in fetal and litters' weight respectively, and 37.0% in fetal survival rate. Decreasing rates were 10.0% in maternal death rate, and 6.9% and 31.3% in pre- and post-implantation loss respectively. Decreasing rates of mercury levels in dams were 67.2% in liver, 57.6% in brain, 47.2% in kidney, 42.1% in spleen and 40.9% in blood. As well, decreasing rates of mercury level in fetuses were 54.9% in all body burden, 55.9% in liver, 46.7% in kidney and 37% in brain, respectively. The number of fetal ossification centers were reduced by 23.8% to 58.0% following simultaneous treatment with 1.0 g/kg garlic juice. These findings indicated that garlic juice effectively inhibited the embryotoxicity of methylmercury in pregnant Fischer 344 rats. (+info)
Abundance of leptin mRNA in fetal adipose tissue is related to fetal body weight.
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Leptin mRNA was measured in adipose tissue of fetal sheep by reverse transcription polymerase chain reaction (RTPCR). Abundance of leptin mRNA relative to beta-actin mRNA in fetal perirenal adipose tissue increased (P<0.02) with gestation, being higher at 144 d (0.73+/-0. 10, n=5) than at 90-91 d (0.40 +/- 0.08, n=6) or 125 d (0.40 +/- 0. 04, n=5) gestation (term approximately 147- 150 d). There was a positive relationship between relative abundance of leptin mRNA (y) and fetal body weight (x) between 90 and 144 d gestation (r(2) =0.27, P<0.01). The slope of the linear dependence of leptin mRNA on fetal weight was 15-fold greater (P<0.001) at 90-91d (y = 2.81x - 1.1, n=6, r(2) =0.71, P<0.025) than between 125-144 d gestation (y = 0.195x - 0.15, n=16, r(2) =0.39, P<0.01). Thus the leptin synthetic capacity of fetal adipose tissue appears to increase in late gestation but this is accompanied by constraint of its sensitivity to fetal body weight. We hypothesise that leptin synthesis in fetal adipose tissue is related to fetal nutrient supply and growth rate. (+info)
Estimation of fetal weight: mean value from multiple formulas.
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Mean fetal weight value from multiple formulas was compared to fetal weight from single formulas. Data were collected on 975 fetuses who had estimation of fetal weight by ultrasonography within 1 week before birth. Improvement in estimation of fetal weight occurred using either the mean value of multiple formulas or the Hadlock BPD/FL/AC, in comparison to fetal volume, BPD/AC, or FL/AC. BPD/FL/AC appeared to provide the best estimate of true weight in terms of overall accuracy and in terms of not showing a trend in either overestimating or underestimating true weight. (+info)
Preimplantation access to maternal insulin and albumin increases fetal growth rate in mice.
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Provision of the maternal factors, albumin and/or insulin to embryos in vitro restores preimplantation morphological development and cell proliferation to that seen in vivo. The hypothesis that the preimplantation effects of insulin or albumin would be reflected in increased fetal growth rate was examined. Two-cell embryos were cultured 48-50 h in medium supplemented with 0.17 micromol/l, 15 micromol/l albumin or 0.17 micromol/l insulin and the resultant blastocysts transferred to pseudopregnant recipients. Fetal and placental mass and skeletal development were determined at E19 or E20 (day 19 or 20 of embryonic development). Preimplantation access to insulin or albumin increased fetal growth by 4-6%. Combining insulin and albumin did not produce a further increment in fetal growth. The fetal growth achieved by providing preimplantation access to insulin, albumin or both was equivalent to that of in-vivo developed blastocysts. The conclusions are that: (i) preimplantation access to maternal insulin and albumin is required for normal fetal growth rates in the mouse and (ii) the increments in inner cell mass cell number and metabolic rates induced by insulin (and possibly albumin) reflect a requirement for maternal growth factors during preimplantation stages to optimize fetal development. (+info)
A mouse model for valproate teratogenicity: parental effects, homeotic transformations, and altered HOX expression.
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Valproate (VPA) is one of several effective anti-epileptic and mood-stabilizing drugs, many of which are also potent teratogens in humans and several other mammalian species. Variable teratogenicity among inbred strains of laboratory mice suggests that genetic factors influence susceptibility. While studying the genetic basis for VPA teratogenicity in mice, we discovered that parental factors influence fetal susceptibility to induced malformations. Detailed examination of these malformations revealed that many were homeotic transformations. To test whether VPA, like retinoic acid (RA), alters HOX expression, pluripotent human embryonal carcinoma cells were treated with VPA or RA and Hox expression assessed. Altered expression of specific Hox genes may thus account for the homeotic transformations and other malformations found in VPA-treated fetuses. (+info)