Morphological substantiation of the potential development of connective tissue disorders and skeletal disproportions after antenatal antigenic stimulation.

Introduction The acquired connective tissue diseases are immunologically mediated inflammatory disorders characterized by abnormal function or structure of components of connective tissue (collagen and elastic fibers, glycosaminoglycans (GAGs) etc.). They are often accompanied by skeletal disproportions. Changes in the joint morphology after antigenic stimulation was studied using hip joints and modelling of prenatal influence of antigens. For this, the antigen (0.05 ml of human normal immunoglobulin) was injected transuterinely intrafetaly subcutaneously in the interscapular area of the rat foetus on the 18th day of its antenatal life under general anesthesia and sterile conditions via laparotomy for the pregnant female (Voloshynʼs method (1981). The control group of rats was injected with 0.05 ml of physiological saline in the same manner.

Fig. 1

Materials and methods The length of femur, shin and foot together with their ratios to coccygeal-parietal size were determined. Joints were fixed, decalcified and dehydrated. Paraffin-embedded tissue specimens were processed by peanut (PNA-HRP), vicia sativa (VSA-HRP) and perca fluviatilis (PFA-HRP) agglutinins, as well as Malloryʼs trichrome, Hart’s elastin and alcian blue (0.2 M MgCl2) stains. Components of the extracellular matrix (ECM) were analyzed by light microscopy (χ100) using the morphometrics and statistical processing. The parameters of intact and control rats did not differ significantly from each other.

Results An increased amount of hyaluronan (till the 14th day), disarranged collagen fibers (seventh–45th day), elastic fibers (till the 45th day), ground substance (till the 14th day), fucose conjugates (30th–45th day) and a decreased amount of sulphated GAGs (till the 14th day), arranged collagen fibers (till the 60th day) in the joint capsule of antigen-stimulated rats were obtained. After antigenic stimulation, the articular cartilage showed a decreased level of mannose- (30th–45th day) and galactose-conjugates (14th–30th day). Together with this, an increased length of femur (45th day), shin (45th day) and foot (30th–45th day), as well as their altered ratios to coccygeal-parietal size (14th–45th day) in the antigen-stimulated rats were determined (Fig. 1). The 30th–45th day of life of the Wistar rat is roughly equivalent to 9–14 human years (childhood and adolescence).

Discussion A decreased amount of sulfated GAGs, mannose- and galactose- containing polysaccharides, which are indispensable for organization of the ECM, in particular collagen, could explain a decreased number of collagen fibers. Hyaluronan overabundance inhibits biosynthesis of collagen and stimulates production of elastic fibers. Changes in the distribution of fibers and ground substance could be considered as morphological signs of the connective tissue dysplasia. An increased amount of fucose-conjugates is also typical for immature tissues. These phenomena might create preconditions for the development of joint dysplasia and skeletal disproportions in children and adolescents.

Keywords joint, antenatal antigenic stimulation, acquired connective tissue diseases, skeletal disproportions, acquired connective tissue dysplasia.

Korrespondenzadresse: Andrii Fedotchenko, Regio Clinic Elmshorn. Department for Geriatric Medicine, Agnes-Karll-Allee 17, 25337 Elmshorn, Germany. E-Mail: [e-mail]

Publication History

Article published online:
08 September 2022