Sexual dimorphism of newborn mouse epithalamus after fractionated X-irradiation at late stage of organogenesis.

Fractionated X-irradiation with 3 x 0.95, 3 x 1.05, 3 x 1.15, or 3 x 1.35 Gy on gestational days 11-13 in the mouse results in two discrete, clearly distinguishable forms of an epithalamic malformation observable on gestational day 18. Type A is characterized by a rhombic shape of the dorsal diencephalic sulcus which first narrows at the occipital edge. The habenular diameters in the plane of the habenular commissure are in the range between 81 and 88% of the control measurements. The anterior colliculi are quite well developed. The type B lesion is characterized by a rather narrow epithalamus with a sandglass-shaped dorsal diencephalic sulcus and habenular diameters that are only about 56 to 64% of the control values. With the exception of the group with the lowest radiation dose (3 x 0.95 Gy), the type B lesion predominates. The B:A ratios are 1.5 and 1.6 in the highest dosage groups, and show the most drastic increase to a ratio of 4.0 after application of 3 x 1.05 Gy. Type B lesions occur in female fetuses at a higher frequency than in males and thus shows a clear-cut correlation with the frequency and severity of neocortical lesions in the same individuals. This is again most marked in the 3 x 1.05 Gy dosage group, where the type B lesion occurs five times more frequently in females than in males. This sexual dimorphism in the reaction pattern of the epithalamus after X-irradiation in utero, can best be explained by postulating a causal link with the forebrain lesions which were recently shown to exhibit similar sexual dimorphism. We therefore postulate a retrograde transsynaptic degeneration of the thalamo-cortical fibres that develop pre-term, which is significantly expressed only after a low X-irradiation dose, but is partly abolished in the higher dosage groups. This leads to hypoplastic alterations of the epithalami, a secondary phenomenon to the neocortical lesions in the animals most affected. The resulting dysfunction of the epithalamus in the immediate neonatal period is then responsible for the preferential death of the animals with B-type lesions and also explains why female mortality is significantly higher than male mortality which occurs only in the 3 x 1.05 Gy dosage group.