TERATOGENESIS (Greek teras, terat[os] the freak, ugliness + genesis origin, an origin) — the mechanism of development of inborn defects.
T. at the person it is studied insufficiently. For an explanation of fundamental mechanisms of development of inborn defects in the person use mainly experimental data. Malformations (see) form preferential as a result of disturbance of an embryonal morphogenesis, to-ry it is carried out at close interaction of a genome of a germ and organism of mother and it is connected with processes of proliferation, migration, differentiation and physiological dying off of cells of a germ. Disturbance of any of these processes involves a deviation from normal development and, therefore, can cause formation of inborn defect.
Etiol. the factors of disturbance of a morphogenesis leading to formation of inborn defects subdivide on endogenous and exogenous. Treat internal causes mutations (see), being the most frequent reason of inborn defects. At the same time the quantity of sporadic mutations increases with increase in age of parents. Such mutations are the cornerstone of the vast majority of chromosomal diseases (see) and the most part is prepotent the inherited malformations.
Exogenous factors are quite often called teratogens, or teratogens. Carry only those factors to them, to-rye break embryonic development, influencing during pregnancy. Unlike them the teratogenic effect of mutagen factors is mediated by mutations in sex cells of parents or more remote ancestors. Teratogens subdivide on physical (radiative and mechanical effects), chemical (the medicines, chemical substances applied in the industry, agriculture and life), biological (viruses, the elementary). Part of them can be an origin of malformations at the person. The teratogenic effect of exogenous factors depends on a chemical structure of a molecule of the agent, his molecular weight, a dose, a way of introduction, a condition of an organism of the pregnant woman, the period of development of an embryo. For impact of ionizing radiation also its look and power matters.
The same teratogen entered in an identical dose by a different animal of the same look into identical durations of gestation not in all cases leads to formation of a malformation that gl.obr. depends on a genotype of an embryo. The listed factors can induce malformations, influencing during various periods of prenatal ontogenesis (see). Prenatal ontogenesis is subdivided into the period of a gametogenesis (progenesis) covering a heating-up period of sex cells (gametes), and the period of a kiyematogenez, to-ry in turn consists of the periods of a blastogenesis, embryogenesis and fetogenez. According to these periods allocate pathology of a gametogenesis, and call defeat of sex cells gametopathies (see). Pathology of a germ, blastocyste, embryo and fruit is called respectively kiyematopatiya (see), blastopatiya (see Anta-nataljkaya pathology), embryopathies (see) and fetopathies (see). In an origin of inborn malformations gametopathies have the greatest value. Malformations of extraembryonic bodies (amnion, an amniotic leg, a vitellicle) and twinning defects (the divided twins asymmetric and symmetric short) belong to effects of blastopatiya. Embryopathies fall on the period of the main organogenesis (at the person — to 56 — the 70th day after conception). During this period the majority of malformations forms, however only those treat embryopathies, to-rye resulted from damage of an embryo. Each malformation has the deadline (the teratogenetic terminatsionny period), during to-rogo a disturbing factor can cause it. Fetopathies seldom result in defects, causing generally a hypoplasia of bodies, immaturity of bodies and fabrics, the general prenatal hypoplasia.
The processes leading to formation of malformations happen at the level of cells, fabrics and bodies. The mechanisms of development and consequently, and processes of T are inherent to each of these levels. depending on the level of disturbing factors are various. Main contents cellular T. disturbances of processes of reproduction (proliferation), migration and determination of cells are. At the heart of T. at the level of fabrics disturbances fiziol lie. a necrosis of separate cellular masses and adhesion of fabrics, the teratogenesis at the level of bodies comes down to disturbance of processes of their growth, anatomic and functional maturing, and also to disturbance of movement of bodies to the place of their final localization. Correctly created bodies in the period of the main organogenesis can be vicious developed in connection with circulator frustration, napr, as a result of the excessive pressure (the amniotic tyazha which are abnormally localized by other bodies).
With malformations rather often occur at persons dizontogenetichesky tumors (see), including malignant. The reasons of such combination are various. In one cases the tumor develops at a dysplasia (see). Such tumors are more often localized in areas where structural and educational processes are especially difficult (splitting, a smykaniye, an otshnurovka, etc.) and where the embryonal proliferative centers most longer remain. A basis for development of these tumors are persistent provisional bodies (Ratke's pocket, urakhus, a chord) or fabrics (a renal blastema, embryonal muscles). In other cases malformations and tumors pathogenetic are connected with the same factor: mutations at the level of chromosomes, napr, at children leukoses (see) and a Down syndrome (see. Down disease ), retinoblastoma (see), a nefroblastoma (see Vilms a tumor); genovariations, napr, epibulbarny dermoid cystomas at Goldenkhar's syndrome, a tumor of adrenal glands and other abdominal organs at Bekvit's syndrome. In some cases the tumors which developed in early ontogenesis can induce development of defects as it is observed at nek-ry forms of coccygeal and sacral teratomas (see). The greatest risk of emergence of dizontogenetichesky tumors is available at syndromes of displaziya and multiple malformations.
Bibliography: Gulkevich Yu. In, and d r» Pretumor processes at children, Arkh. patol., t. 36, No. 3, page 3, 1974; The Teratology of the person, under the editorship of G. I. Lazyuk, M., 1979; Wilson J. G. Environment and birth defects, N. Y., 1973.
G. I. Lazyuk.