published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Anatomy / Master / Master of Philosophy

Polychlorinated biphenyls (PCBs) are a class of bioactive chemical once used in industrial applications, but which now contaminate the world environment. PCBs are lipophilic with few natural degadatory mechanisms, and thus they accumulate in human and animal tissues, and are passed to subsequent generations via transfer between mother and offspring. Research has shown that PCBs can interfere with brain and sexual organ development, and adult sexual behaviors and reproduction. However, previous studies produced contradictory results based on the dose and method of administration, species, and the age at exposure. The research detailed in this thesis elucidates the effects of prenatal exposure to low levels of a commercial mixture of PCBs, Aroclor (A) 1221, on female reproductive function. The studies undertaken in this dissertation focus on three areas relevant to understanding long-term effects of PCBs on reproductive physiology in female rats: (1) developmental effects in two generations, (2) sexual behaviors in the first generation, and (3) gene expression in the first generation. In the first research section of this dissertation, the sexual and somatic development of PCB-exposed animals is investigated in first (F1) and second (F2) generation females. Dose-dependent effects are observed in both generations, and a greater number of endpoints are significantly affected in the F2, including circulating hormone levels and uterine and ovarian weight. The second research section of the dissertation explores whether sexual behaviors in the first generation of exposed animals are altered by A1221, using a paced mating paradigm designed to elucidate female-typical behaviors. Several salient behaviors are affected by PCB exposure, including likelihood to mate, mating trial pacing, and stress-related vocalizations. The third research chapter discusses the results of a genomewide microarray assay performed on the preoptic area of the brain. The preoptic area is a neuroendocrine control center implicated in regulation of reproductive physiology and behavior. Taken together, these results suggest that A1221 has long lasting and trans-generational effects on the development and behavior of exposed females, accompanied by altered gene expression in a neuroendocrine region of the brain. These findings have implications for female reproductive health and reproductive success in wildlife and humans.

published_or_final_version / Medicine / Master / Doctor of Medicine

A mouse testis cDNA library was screened with an oligonucleotide probe corresponding to a sequence in the 5$ sp prime$ region of mouse N-cadherin cDNA. A composite clone containing three individual cDNAs was isolated. These included a 711 bp cDNA encoding part of mouse testicular N-cadherin, an unidentified 392 bp cDNA, and a 1500 bp cDNA encoding the mouse homologue of a human breast tumor autoantigen. / The cadherins, the influenza strain A hemagglutinins, and the fibroblast growth factor receptors are three different families of integral membrane glycoproteins that harbour the amino acid motif histidine-alanine-valine (HAV) in regions involved in protein-protein interactions. In order to identify other proteins that possess the HAV motif in functionally important regions, the SwissProt database was searched using a consensus sequence derived from the cadherins, influenza strain A hemagglutinins, and fibroblast growth factor receptors. This search identified the $ alpha$ chains of the HLA class I histocompatibility antigens as a fourth family of integral membrane glycoproteins with an HAV-containing region that is involved in a protein-protein interaction. (Abstract shortened by UMI.)

Thesis (Ph. D.)--University of Hong Kong, 2008. / Also available in print.

Thesis (Ph. D.)--Vrije Universiteit te Amsterdam, 1996.

Thesis (doctoral)--l'Ecole Pratique des Hautes Études [France], 1997. / Title from Summary page ; description based on resource as of 2005-06-17. Thèse pour le Doctorat de l'Ecole Pratique des Hautes Etudes, IVe section. Includes bibliographical references.

Thesis (M.S.W.)--University of Hong Kong, 1994. / Includes bibliographical references (p. 197-212).

Thesis (Ph. D.)--Vrije Universiteit te Amsterdam, 1996.