Thesis (Ph.D)--Boston UniversitySixty-six non-pedigreed gravid albino hamsters (Mesocricetus auratus) were exposed to a single dose of hypoxia of five to ten hours duration between the seventh and tenth days of gestation in order that the period during which the embryonic excretory system is most sensitive to the action of the teratogen might be determined. Maximum sensitivity occurred during the 10 hour interval between 1:30 - 11:30 a.m. on the 8th day of development (post ovulatory) which is coincident with the period of most rapid differentiation, morphogenesis, and changes in body form (twisting and flexing). The oxygen pressure was equivalent to 40.5 to 48.6 mm. Hg or 25.5 to 30.6 percent of normal atmospheric oxygen. Hypoxia was effected by use of an improvised altitude chamber consisting of two large-sized dessicating jars, a supply of compressed air, a vacuum pump, and a mercury manometer. The reduction of atmospheric pressure was approximately that found at an altitude of 30,500 feet.
Three hundred and five embryos were examined for gross abnormalities after 15-16 days of development. One hundred eighteen embryos were sacrificed between 9 1/2 - 12 1/2 days of gestation and examined histologically for abnormalities of the developing excretory system.
The array of congenital abnormalities detected was related to the time and duration of exposure of the maternal organism to the hypoxic insult. Mortality and morbidity rates increased as the duration of hypoxia increased. Abnormalities identified included exencephalocoel, micrognatha, hare-lip, vertebral and rib defects, limb abnormalities, cryptorchidism, renal defects, hydroureter, uterine aplasia, herniated diaphragm, abnormal spinal cord, and one instance of a double testis on one side. The renal defects included renal agenesis, discontinuity of the mesonephric duct, premature and ectopic termination of the mesonephric duct, development of accessory ducts from the mesonephric duct, multiple metanephric pelves forming about combinations of accessory ducts, mesonephric duct and ureteric buds, and malpositioning of the metanephroi.
Evidence is presented to indicate that the mesonephric duct of the hamster grows by elongation of a growing tip rather than by accretion of new cells from the urogenital ridge during its posterior development. The mesonephric duct, accessory ducts (elongate diverticulae from the mesonephric ducts in areas other than that which normally gives rise to the ureter), and the ureteric tip are all capable of inducing development of the metanephric blastema. It is proposed that the collecting ducts of the chick mesoenprhos are homologous with the accessory ducts and the ureteric buds of the mammal. The abnormalities of development of the mesonephric duct are believed to be due to inhibition of growth and/or differentiation and the incompatibility of localized areas of development with normal mesonephrogenic tissue.
It is postulated that normal surface related phenomena involved in cell migration or guidance systems have been interrupted. It is proposed that this may be the result of simple retardation of development, inability of the embryo to complete appropriate biochemical syntheses, or accumulation of toxic substances. Alteration in permeability of placental blood vessels might also be a complicating factor.
It is suggested that the use of non-pedigreed animals with genetic parameter limited only by the similarity in coat color has possibly afforded a greater variety of effect than would have been obtained under more closely controlled genetic conditions. [TRUNCATED
