We have previously shown that myo-inositol depletion in the embryonic tissue at a critical stage of organogenesis has a crucial role in hyperglycemia-induced embryopathy. This study tested whether myo-inositol depletion in early organogenesis contributes to the pathogenesis of streptozocin-induced diabetic embryopathy. Rats were made diabetic by streptozocin administration before conception, and the diabetic rats were treated with diet supplemented by 2% myo-inositol or insulin from 6 to 11 gestational days during the period of maximum teratological susceptibility. In each group on the 11th gestational day, growth retardation and incidence of malformations were recorded, and myo-inositol and sorbitol content in the embryonic and extraembryonic tissues were examined. In diabetic rats, the myo-inositol content of the embryos was decreased by 36% (P less than 0.01) compared with control rats, and there was growth retardation (crown-rump length 3.37 +/- 0.04 vs. 3.87 +/- 0.03 mm, P less than 0.01; somite no. 27.5 +/- 0.2 vs. 29.1 +/- 0.2, P less than 0.01) and a significantly increased incidence of the neural lesions (17.6 vs. 1.9%, P less than 0.01). Insulin treatment resulted in near normalization of maternal serum glucose and complete restoration of myo-inositol content in the embryos with significant improvement of the growth retardation (crown-rump length 3.55 +/- 0.06 vs. 3.37 +/- 0.04 mm, P less than 0.05; somite no. 28.2 +/- 0.13 vs. 27.5 +/- 0.2, P less than 0.05) and a significantly lowered incidence of neural lesions (2.5 vs. 17.6%, P less than 0.01) compared with those of the untreated diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
We have previously shown that long-term exposure to medium containing insulin-induced hypoglycemic serum during the early phase of organogenesis can adversely affect embryonic development in rat embryo culture and that these effects were mediated through the interruption of glycolytic flux that constituted the principal pathway at this embryonic stage. Further experiments were performed to examine whether brief exposure to the hypoglycemic medium during critical developmental periods would have adverse effects on embryogenesis during embryo culture not only in normal but also in high glucose concentrations. Rat embryos in the early head-fold stage (9.5 days gestation) were grown in vitro for 48 h until neural tube closure occurred; dysmorphogenic lesions were not elicited in either the basal culture medium containing 6.6 mM glucose (control medium) or the hyperglycemic medium supplemented with glucose at a concentration of 33.3 mM. Hypoglycemic mediums (2.2-2.5 mM glucose) were prepared from the serum of rats given insulin intraperitoneally. Postimplantation embryos (in early neural tube formation) were briefly exposed (1 h) to hypoglycemic medium on day 10.3 of gestation during the basal culture. After exposure to the hypoglycemic medium for 1 h during culture in the control medium, embryos showed minor growth retardation and dysmorphogenic lesions (7.1% open neural pores). Exposure to the hypoglycemic medium for 1 h during culture in hyperglycemic medium suplemented with a subteratogenic concentration of glucose (33.3 mM) resulted in greater growth retardation and increased occurrence of dysmorphogenic lesions (17.3% open neural pores).(ABSTRACT TRUNCATED AT 250 WORDS)
The incidence of malformation is increased in infants of hyperthyroid or hypothyroid woman. Although many papers reported that the fetus is insulted from maternal thyroid hormone, the placenta (maternalfetal barrier) is not yet fully developed before 11.5 days of gestation in rat embryos, suggesting the effect of thyroid hormone on early rat embryogenesis. This study was, therefore, undertaken to investigate whether excess or lack of thyroid hormones would affect early embryogenesis in rat embryo culture. Malformations including open neuropore and microencephaly were observed in 10 of 30 embryos incubated in hyperthyroid serum, and in 12 of 42 cultured in T3-enriched normal serum. Similar malformations were observed in 14 of 42 embryos cultured in hypothyroid serum and in 10 of 30 cultured in hypothyroid serum supplemented with T3. The frequencies of these malformations were significantly higher than in the control embryos (0 in 72 embryos) cultured with normal rat serum. These results suggest that the maternal thyroid status might play an important role for the complication of fetal malformations during early gestational period.Increased incidence of congenital malformations has been reported in infants of both hyperthyroid and hypothyroid women. Maternal hyperthyroidism has been suspected as a potential cause of mal¬ formations in offspring (1). On the other hand, abortion rate, neonatal mortality, congenital anomalies, and delay in mental and fine motor de¬ velopment in infants of mothers with 'hypothyroxinemia' and inadequate thyroid replacement ther¬ apy has been reported (2). Although the fetal hypothalamic-pituitary-thyroid axis develops and functions independently of maternal thyroid status, the effect of maternal thyroid hormones on fetal devel¬ opment, brain function and growth are controver¬ sial (3, 4). There have been only few reports, how¬ ever, on the influence of thyroid hormones on early embryogenesis (5, 6). We have recently de¬ veloped a whole embryo culture system and stu¬ died the effect of glucose on early embryogenesis in this system (7). In this study, we have investi¬ gated whether excess or lack of thyroid hormones could affect early embryogenesis in rat embryo cul¬ ture. Materials and MethodsRat embryo culture was performed by the methods of New (8) and detailed methods have been previously de¬ scribed (9). Embryos were obtained from randomly bred Wistar rats (Shizuoka Laboratory Animal Centre, Shi¬ zuoka, Japan) on day 9 'A. Pregnancy was timed from mid¬ night preceding the morning when sperm were present in the vaginal smear. On day 9 '/. of gestation, with the embryo at the early head-fofd stage, pregnant rats were killed by cervical dislocation. Conceptus were excised, floated in Petri dishes containing Hanks' balanced salt solution (Gibco, Grand Island, NY), and freed of decidua with a fine jeweller's forceps under direct visualisation with a dissecting microscope. Reichert's membrane was opened and intact embryo units (i.e. embryos together with their visceral yolk sac, amnino, an...
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