The presence of persistent organic pollutants, including the pesticide toxaphene, has been reported even in remote regions such as the Arctic and is becoming a health concern. The technical mixture of toxaphene contains over 800 different congeners; however, the numbers decrease along the food chain. Only two major congeners, 2-exo, 3-endo, 5-exo, 6-endo,8,8,9,10,10-octachlorobomane (T2) and 2-exo, 3-endo, 5-exo, 6-endo,8,8,9,10,10-nonachlorobomane (T12) have been found in humans. Information on the embryotoxicity of toxaphene is based only on studies using the toxaphene technical mixture and not its major congeners. Diabetes mellitus, one of the most common maternal illness resulting in congenital defects, is now on an upgrowth trend in many native communities. Xenobiotics, such as toxaphene, may induce interactive effects with hyperglycemia, a teratogenic metabolic agent. / In the present study, the relative dysmorphogenic effects of the toxaphene technical mixture or its congeners (T2 and T12) and the interactive effects of these compounds and high glucose concentrations were investigated using rat embryo culture. Early stage embryos (0--2 somite) were treated with three different doses of the toxaphene technical mixture, T2, T12, or 50:50 mixture of T2 and T12 and incubated in normal or hyperglycemic culture media for 48 h. (Abstract shortened by UMI.)

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Thesis (Ph. D.)--University of Hawaii at Manoa, 2004. / Includes bibliographical references (leaves 92-105). / Also available by subscription via World Wide Web / xv, 105 leaves, bound ill. 29 cm

A delicate balance of steroid and gonadotrophic hormones is essential for intrafollicular oocyte maturation and successful fertilization and embryonic development. Previous studies have demonstrated that a superovulatory dose of pregnant mare serum gonadotrophin (PMSG) has excessive gonadotrophic activity and alters intrafol1icular steroid hormone levels. In a series of four experiments, the morphology of oocytes and embryos retrieved from immature rats, treated with either a low or high dose of PMSG, and mature, cycling rats was compared to determine whether a superovulatory dose of PMSG has an adverse effect on oocyte maturation and subsequent fertilization and embryonic development in immature rats. Morphological criteria for the assessment of intraoviductal oocyte aging were established in the first experiment. During intraoviductal aging, progressive morphological changes directed by the intrinsic developmental program of the oocyte were observed. Further alterations in morphology were attributed to abnormalities of cytoskeletal function. In the second experiment, no difference in morphology was observed between oocytes retrieved from immature rats treated with either 4 or 40 IU PMSG. When compared with mature rats, changes attributable to cytoskeletal instability were observed in aged oocytes from immature rats treated with both doses of PMSG. This was concluded to be a manifestation of altered intrafollicular oocyte maturation as a result of the administration of exogenous gonadotrophin. In the third and fourth experiments, delayed fertilization and a significant reduction in fertilization rate were observed in superovulated, immature rats. The major cause of fertilization failure was determined to be intraoviductal oocyte aging. A significant increase in abnormal embryos was observed as a result of parthenogenetic activation of the aged oocytes. Abnormal, fertilized embryos retrieved from the superovulated group were concluded to be the manifestation of delayed fertilization. In conclusion, the major effect of a superovulatory dose of PMSG on oocyte fertilizability and embryonic development was intraoviductal oocyte aging and delayed fertilization. Changes attributed to altered intrafol1icular maturation were manifested during oocyte aging in immature rats treated with either the low or high dose of PMSG. / Medicine, Faculty of / Obstetrics and Gynaecology, Department of / Graduate