Effect of injected human immunoglobulins on fetal rat development. Spinal, neural and osseous changes

Abstract

Rabbit anti-rat-brain serum immunoglobulins injected into pregnant rats on the ninth, tenth, eleventh or twelfth day of gestation resulted in a fetal resorption rate 15 to 30 times higher than that found in normal untreated pregnant rats. Human serum immunoglobulins obtained from normal postpartum mothers produced a similar percentage of fetal resorption when injected by the same routes into pregnant rats of the same gestational age. In neither of the above experiments were malformations detected among the delivered 20-day fetuses. Injection of human serum immunoglobulins obtained from mothers of children with spina bifida manifesta into pregnant rats along similar routes and periods gave comparable fetal resorption rates. Injection of the above immunoglobulin into the lumen of the uterus adjacent to implantation sites gave a low fetal resorption rate and produced varying degrees of skeletal and soft tissue malformations among the viable survivors.The only difference which could be discerned between normal postpartum immunoglobulins and those obtained from mothers of spina bifida manifesta children was characterized in the latter by a two-fold increase in the IgG levels and the immunoelectrophoretic reactivity of its immunoglobulins with human spinal cord antigens, The developmental defects observed were: 1. Cranialthinning and bleb formation of skull bones; widening of the foramen magrium; descent of the obex closer to the foramen magnum. 2. Skeletal-delayed or inhibited calcification of the bodies and spinous processes of the thoracic and lumbar vertebrae; widening of the vertebral canal and central canal of the spinal cord.Alterations in the growth patterns of developing embryos and fetuses have been induced by exposing them to tissue antiserum. Brent et al. ('61) demonstrated that rabbit anti-rat kidney serum injected intravenously into pregnant rats on the eighth day of gestation resulted in severe skeletal congenital malformations in 100% of the fetuses. McCallion ('68) reported that rabbit anti-chicken brain serum placed on 33-hour incubated chick embryos and incubated for a further five to seven days resulteld in the formation of localized or generalized spina bifida in 10% of the surviving embryos. Kamrin ('70) reported that immunoglobulins from mothers of children with spina bifida manifesta produced lesions suggestive of spina bifida and the Arnold-Chiari syndrome when injected into rats on the tenth day of ges-ANAT. REC., 173: 173-180.tation. It is evident in all of these experiments that the exogenous immunoglobulins arrested or slowed the differentiation of somite cells to cartilage and their subsequent calcification. These experiments also appear to confirm the findings of Holtzer et al. ('55, '61, '68) that ( a ) using somite tissue taken from chick embryos and grown in the absence of spinal cord or notochord, the production of cartilage will be prevented; (b) cartilage could be induced to appear by the addition of embryonic intermediate somitic mesoderm (from which the kidney forms) and...