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Hyperthermia is teratogenic to human and animal embryos and induces mainly anomalies of the nervous system. However, the teratogenic mechanism is poorly understood. Mammalian embryos are known to switch from anaerobic to aerobic metabolism around the time of neural tube closure. This critical event might be sensitive to hyperthermia. The objective of the present study was to evaluate the ultrastructural changes of the mitochondria of the neuroepithelium (NE) of rat embryos following maternal exposure to hyperthermia. Pregnant rats were heat stressed for an hour on gestation day (GD) 9 and embryos were examined by electron microscopy on GD 10. NE presented extensive apoptosis. Intercellular junctions were weakened and copious cellular debris projected into the ventricle. The mitochondria were of diverse size and shape. Most of them were swollen and had short cristae and electron dense matrix. Hydropic changes were also observed in numerous mitochondria. Lipid-laden mitochondria were found in the apical portions of neuroblasts. The mesenchyme (ME) of heat-treated embryos showed paucity of cells and only as frequent apoptosis as the controls. Their mitochondria also showed changes similar to those of the NE. Additionally extensive lipid accumulation was observed in and in the vicinity of mitochondria, often surrounded by short strands of endoplasmic reticulum. Whereas mitochondrial pathology was associated with profound apoptosis in the NE, growth restriction and lipid accumulation accompanied mitochondrial changes in the ME. The results of this study indicate that the embryonic response to maternal heat shock is tissue-specific and morphologically distinct in this species.

Neural tube defects (NTD) are mainly of multifactorial origin. Maternal treatment with valproic acid (VPA) during pregnancy induces NTD in susceptible fetuses. Elevated levels of homocysteine are observed in pregnancies with NTD. The mechanism by which homocysteine might cause NTD is unknown. The aim of this study was to determine if homocystine would augment VPA-induced exencephaly in an experimental model. Groups of mice were injected (IP) on gestational day 8 (GD) with a single dose of 75 mg/kg of l-Homocystine (HC) or a proportionate volume of saline, followed by a single dose of 600 mg/kg of VPA or an equal volume of saline. In a second experiment, mice were treated with a daily dose of 75 mg/kg of HC or an equal volume of saline (IP) from GD 5 and continued through GD 10. These animals had a single exposure to 600 mg/kg of VPA or saline (IP) on GD 8. All animals were killed by cervical dislocation on GD 18. Plasma homocysteine, folate and vitamin B12 were determined on GD 8 and GD 10 from single and multiple dose groups of mice, respectively, from additional experiments. The VPA and HC+VPA induced significantly higher rates of embryonic resorption and intrauterine growth retardation (IUGR) than HC or saline alone. HC + VPA groups had significantly more numerous fetuses with severe IUGR than HC alone or VPA alone groups. Both single and multiple doses of HC augmented VPA-induced reduction in fetal body weight. Successive doses of HC did not augment the rate of IUGR more significantly than a single dose of HC. Incidence of exencephaly was significantly enhanced in the HC + VPA groups compared to that in the HC or VPA alone groups. HC alone was not teratogenic. Plasma homocysteine levels increased several fold both in HC and HC + VPA groups and the increase was not particularly more marked in multiple dose groups than in the single dose groups. VPA did not elevate homocysteine concentration. Both FA and vitamin B12 concentrations were reduced by VPA, HC and HC + VPA, but HC and VPA when combined did not produce an additive effect on vitamin levels. These data indicate that HC and VPA interact in neurulation stage embryos, affect fundamental processes of closure of the neural tube and lead to enhanced incidence of NTD.

The objective of this study was to evaluate the ultra-structural changes in the urinary bladder of diabetic rats in relation to disease duration since the morphological bases of diabetes-induced bladder dysfunction are poorly understood. Urinary bladders were examined chronologically by electron microscopy in a female Wistar-rat model of streptozotocin-induced diabetes mellitus and compared to control samples. Numerous dark mitochondria with swollen cristae and electron lucent, large, calcified and degenerated mitochondria were observed first in the urothelium. Intraepithelial capillaries surrounded by thick collagen were also present. Gap junctions between myocytes were interrupted or extensively widened with reduced mitochondria and caveolae. Collagen accumulation, degenerated nerve fibres and myelin bodies were seen between myocytes with increased collagen content and frequent mast cells, phagocytes and lymphocyte aggregates in the stroma. All ultra-structural lesions became augmented with longer duration of diabetes. Diabetes induces time-dependent pathologic changes in the urinary bladder of rats that might account for bladder dysfunction.

Collagen and blood vessels of the urethral submucosa of ovariectomized rats were studied following 28 daily subcutaneous injections of 17-s estradiol (n=6, group 1), medroxy-progesterone acetate (n=6, group 2), both drugs (n=6, group 3) or vehicle (n=6, control) and after sham surgery without castration or injection (n=6). Investigations included the immunohistochemistry of estrogen and progesterone receptors and collagen fibres, Western blot analysis of collagen types I and III and counting periurethral vessels by light microscopy. Our results showed positive immunostaining with estrogen, progesterone and collagen types I and III in all samples. Collagen type I and III levels were lower in the controls than in the sham group. The other groups showed increases (2>3>1) over the controls with a relatively higher increase in type III. The type I/III collagen ratio progressively decreased (control>1>2>3) below sham levels. The mean vessel count was significantly lower in control than in sham animals (P