Critical period for induction of congenital hydrocephalus and dysplasia of subcommissural organ by prenatal X-irradiation in rats

Summary A single whole-body X-irradiation of pregnant Wistar rats at a dose of 1.05 Gy at 10.30, 12.30 and 14.30 h respectively, of gestational day 10 resulted in significantly high incidences of hydrocephalic offspring. No hydrocephalic offspring resulted from X-irradiation of pregnant rats with 1.05 Gy at 16.30 h whereas a dose of 1.22 Gy at 16.30 h resulted in a low but statistically significant incidence of hydrocephalus. Neither 1.05 Gy nor 1.22 Gy X-irradiation of pregnant rats at 18.30 h resulted in any hydrocephalic offspring. Dysplasia of the subcommissural organ was noticed in all the hydrocephalic brains histologically examined.     

Sex-dependent action of prenatal fractionated X-irradiation in the mouse. Biochemical findings.

X-irradiation of pregnant NMRI-mice on gestational days 11-13 with 3 x 10.5 Gy increased postnatal mortality of the female offspring only. Weights, protein content and acetylcholinesterase, as well as Na,K-ATPase activities in the brains of all treated offspring, were changed. There were, however, no differences between females and males with respect to these parameters.     

Marked depression of radiation-induced emesis by olfactory bulbectomy or pre-exposure using low doses

Acute emetic response to relatively low-doses of X-irradiation on suncus (Suncus murinus) was examined. The behaviors recorded for each subject, using a video-cassette recorder system, were (1) the number of emesis, during exposure to a dose of 3.0 Gy; (2) emesis threshold. Results showed that the emetic threshold was observed at 0.85 Gy, and the number of radioemesis during exposure was 29. However, the observed threshold dose became 2.22 Gy following olfactory bulbectomy. The emetic number decreased significantly (p<0.01), and reached a value one-fourth of the sham-control. The bulbectomized suncus showed a resistance to X-irradiation. Furthermore, I examined whether the animals could also acquire radio-resistance when they were subjected to a brief of dose X-ray (0.3 Gy) prior to a exposure to 3.0 Gy. Results showed that brief pre-exposure increased the observed threshold, a pattern that was exactly the same as shown in the bulbectomized animals. Increasing the pre-exposure dose further to 0.45–0.60 Gy, however, resulted in the complete disappearance of the effect. These results suggest that only the mice pre-irradiated with 0.30 Gy acquired resistance to radiation-induced emesis.     

Sex-dependent action of prenatal fractionated X-irradiation in the mouse. Biochemical findings

Summary X-Irradiation of pregnant NMRI-mice on gestational days 11–13 with 3×1.05 Gy increased postnatal mortality of the female offspring only. Weights, protein content and acetylcholinesterase, as well as Na, K-ATPase activities in the brains of all treated offspring, were changed. There were, however, no differences between females and males with respect to these parameters.We gratefully acknowledge the assistance of Miss C. Gutmann.     

Sexual dimorphism of mouse fetal brain lesions after X-irradiation prior to gonadal differentiation

Fractionated X-irradiation of gestational days 11-13 in the mouse, with doses between 3 x 1.05 and 3 x 1.33 Gy resulted in rosette-like clusters of primitive ependym-resembling cells dispersed within the cortex walls. Quantification of these abnormalities showed a general prevalence in the female fetuses, especially due to the larger number of rosettes in the females than in the males. It was concluded that X-irradiation acts on sex-specific differentiation steps, which are fully developed at the beginning of the fetal period. As it was recently speculated that these are linked to an early divergence of gene expression between the sexes, we suggest that X-chromosome damage may be involved in the pathogenesis of the dimorphic lesion pattern. While, in principle, this will valid for any fetal tissue, it only becames evident in the forebrain because of the outstanding relationship between cell necrosis and rosette development in this specific organ.     

Sexual dimorphism of mouse fetal brain lesions after X-irradiation prior to gonadal differentiation

Summary Fractionated X-irradiation of gestational days 11–13 in the mouse, with doses between 3×1.05 and 3×1.33 Gy resulted in rosette-like clusters of primitive ependym-resembling cells dispersed within the cortex walls. Quantification of these abnormalities showed a general prevalence in the female fetuses, especially due to the larger number of rosettes in the females than in the males. It was concluded that X-irradiation acts on sex-specific differentiation steps, which are fully developed at the beginning of the fetal period. At is was recently speculated that these are linked to an early divergence of gene expression between the sexes, we suggest that X-chromosome damage may be involved in the pathogenesis of the dimorphic lesion pattern. While, in principle, this will be valid for any fetal tissue, it only becames evident in the forebrain because of the outstanding relationship between cell necrosis and rosette development in this specific organ.We are greatly indebted for the technical assistance of Mrs E. Senft, Mrs I. Hempfling and Mrs K. Pfaff.     

Persistance of maternally derived3H-estradiol in fetal and neonatal rats

Summary Injection of³H-estradiol into pregnant rats resulted in fetal blood radioactivity 5 times higher than in maternal blood. Significant amounts of³H-estradiol were found in fetal blood 24 h later and in the offspring 5 days after birth.Supported by NIH Grant HD 08844.     

Increase in the survival time of mice exposed to ionizing radiation by a new class of free radical scavengers

N-acyl dehydroalanines react with and scavenge mainly superoxide radical (O-2.) and hydroxyl radical (HO.). The ortho-methoxyphenylacetyl dehydroalanine derivative, indexed as AD-20, protects mice against damage resulting from total body X-irradiation, as measured by the increase in their survival time. AD-20 increases the LD50 at 30 days from 6.1 to 7.3 Gy in animals exposed to a wide range of X-rays (6 to 10 Gy). The dose reduction factor (D R F) of AD-20 is 1.20. We postulate that such radioprotective effect may result from its free radical scavenging activity.     

Frühe Stadien der Erholung bei bestrahlten ratten und Mäusen

Summary A split dose experiment was performed in 12-, 24- or 32-day-old Wistar rats. About 4000 animals were used. The first dose given was 200 R whole-body X-irradiation in the 2 younger groups, and 260 R in the oldest group. At intervals from 6–48 h after the first, a second irradiation was given in order to estimate the LD50(30). No recovery was seen in terms of the LD50(30) differences between preirradiated and normal animals 6 h after the first dose. At the 12 h interval marked recovery was found in all 3 age groups, but less recovery was apparent at the later intervals.     

Superior avoidance learning in the offspring of rats treated with an anabolic steroid during pregnancy

Summary Treatment of pregnant rats with stanozolol, an anabolic steroid, increases the avoidance learning of the offspring at maturity.     

Increase in the survival time of mice exposed to ionizing radiation by a new class of free radical scavengers

Summary N-acyl dehydroalanines react with and scavenge mainly superoxide radical and hydroxyl radical (HO^.). The ortho-methoxyphenylacetyl dehydroalanine derivative, indexed as AD-20, protects mice against damage resulting from total body X-irradiation, as measured by the increase in their survival time. AD-20 increases the LD₅₀ at 30 days from 6.1 to 7.3 Gy in animals exposed to a wide range of X-rays (6 to 10 Gy). The dose reduction factor (D R F) of AD-20 is 1.20. We postulate that such radioprotective effect may result from its free radical scavenging activity.     

Prenatal stress and postnatal androgen: Effects on reproduction in female rats

Summary Heat-restraint stress applied to pregnant rats during the last trimester disrupts oestrus cycles in female offspring and alters adrenal, ovarian and uterine weights at autopsy. Sexual receptivity is left intact. Prenatal stress may operate by increasing exposure of fetal females to androgens in utero.     

Prenatal stress and postnatal androgen: effects on reproduction in female rats

Heat-resistant stress applied to pregnant rats during the last trimester disrupts oestrus cycles in female offspring and alters adrenal, ovarian and uterine weights at autopsy. Sexual receptivity is left intact. Prenatal stress may operate by increasing exposure of fetal females to androgens in utero.     

Treatment of pregnant rats with haloperidol delays the onset of sexual maturation in female offspring

Summary Treatment of pregnant rats with haloperidol (1 mg/kg/day) during the last week of gestation induces a significant delay in sexual maturation of female offspring.This study was supported by a Canadian MRC grant, No. MA-7131.     

Dysplasia of subcommissural organ in congenital hydrocephalus spontaneously occurring in CWS/Idr rats

The subcommissural organ (SCO) of the congenital hydrocephalus spontaneously occurring in CWS/Idr rats was severely reduced in size and displaced at some distance from the anterior end of the cerebral aqueduct. The cerebral aqueduct of the hydrocephalic rats was open throughout its total length during postnatal days 1-20, though it was somewhat narrower at its middle region than in the normal brain.     

Ovarian stimulation by exogenous gonadotrophins in fetal ethanol-exposed immature rats

Adult pregnant rats were given either an ad libitum liquid diet containing 5% ethanol, a pair fed liquid diet or an ad libitum diet of rat chow and water administered throughout pregnancy and during the nursing period. The female offspring received either pregnant mare's serum gonadotrophin (PMSG) or PMSG followed by human chorionic gonadotrophin (hCG) at 30 days of age. The ovaries of fetal ethanol-exposed animals responded greater to the exogenous gonadotrophins with enhanced ovarian weights, increased numbers of ova shed, greater numbers of corpora lutea and antral follicles, and higher serum progesterone levels than in animals exposed to the control diets during gestation.     

Ovarian stimulation by exogenous gonadotrophins in fetal ethanol-exposed immature rats

Summary Adult pregnant rats were given either an ad libitum liquid diet containing 5% ethanol, a pair fed liquid diet or an ad libitum diet of rat chow and water administered throughout pregnancy and during the nursing period. The female offspring received either pregnant mare's serum gonadotrophin (PMSG) or PMSG followed by human chorionic gonadotrophin (hCG) at 30 days of age. The ovaries of fetal ethanol-exposed animals responded greater to the exogeneous gonadotrophins with enhanced ovarian weights, increased numbers of ova shed, greater numbers of corpora lutea and antral follicles, and higher serum progesterone levels than in animals exposed to the control diets during gestation.     

Dysplasia of subcommissural organ in congenital hydrocephalus spontaneously occurring in CWS/Idr rats

Summary The subcommissural organ (SCO) of the congenital hydrocephalus spontaneously occurring in CWS/Idr rats was severely reduced in size and displaced at some distance from the anterior end of the cerebral aqueduct. The cerebral aqueduct of the hydrocephalic rats was open throughout its total length during postnatal days 1–20, though it was somewhat narrower at its middle region than in the normal brain.     

Étude cytologique d'une translocation chromosomeY-autosome chez la souris

Summary A male mouse with one translocation involving theY-chromosome has been observed in the F1 offspring of a male mouse given 300 R of X-irradiation. 6 types of spermatocytes were recorded. Our observations appear to confirm that the acrocentricX of the mouse associates end-to-end with theY at its centromeric end.     

Effect of glucocorticoids injected into pregnant female mice and rats on weight of male sexual glands in adult offspring and testosterone level in fetus in genotype-dependent

Injection of corticosterone into CBA/Lac, C57BL/6J and BALB/c mice, or hydrocortisone into aggressive and domesticated rats, on days 16 and 18 of pregnancy decreased the weight of sexual glands in adult male offspring of the C57BL/6J and domesticated mothers but increased these values in male offspring of the CBA/Lac and aggressive mothers. When injected into pregnant aggressive and domesticated rats, corticosterone affected testosterone levels in 21-day-old male fetuses. The changes were also genotype-dependent and followed the course of changes in the weight of the accessory sex glands in adults. It is suggested that glucocorticoids given during the prenatal period can effect plasma testosterone levels of male fetuses and the development of the sexual glands in a genotype-dependent manner.