Peroxisome proliferator-activated receptors (PPARs), phthalates and reproduction in the female zebrafish (Danio rerio)

Abstract

Peroxisome proliferator-activated receptors are nuclear transcription factors that mediate a wide array of physiological processes in mammals including reproduction. The objective of this thesis was to characterize the presence, regulation and actions of members of the PPAR family in the ovary of the zebrafish (Danio rerio). Gene expression of all five PPARs, pparαA, pparαB, pparβA, pparβB and pparγ, was detected in ovarian follicles at different stages of development. The expression of pparαA, pparβB and pparγ declined as the follicles developed. Human chorionic-gonadotropin, a luteinizing hormone analog, was shown to decrease gene expression of pparαA, while activators of the Protein Kinase C pathway downregulated expression of pparαA,pparαB and pparβB in full grown ovarian follicles. Intraperitoneal injections of the known PPAR ligands, diethylhexyl phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) reduced the numbers of eggs spawned by adult female zebrafish and this was attributed to a disruption in ovulation. Fish injected with either DEHP or MEHP had reduced expression of the nuclear progesterone receptor (npr) gene, and fish injected with MEHP had reduced expression of a distintegrin and metalloproteinase with thrombospondin motifs 1 (adamts1) gene expression, two key players in the ovulation process. This study provides insight into the physiological pathways that are regulated by the PPAR family of transcription factors in teleost ovaries.