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Estradiol and Endocrine Disrupting Compounds Effects on Echinoderm Reproduction and Development: Developmental Sensitivities and Defense Mechanisms

Abstract

Marine invertebrates are exposed to endocrine disrupting compounds (EDCs) and must utilize defense mechanisms to survive and reproduce; however, little is known about the effects of EDCs on marine invertebrates. Using the sea urchin developmental model, we ascertained that embryos were sensitive at environmentally relevant concentrations to estradiol, ethynylestradiol, 4-octylphenol, tributyltin and o,p-DDD in a stage-specific manner with early embryos being the most sensitive.  Incubation with tamoxifen, a selective estrogen receptor modulator, 'protected' the embryos from estrogenic toxicity suggesting a receptor-mediated mechanism of toxicity.  Estradiol is produced during gastrulation and binds to a low-capacity, low-affinity receptor. Maternal exposure to EDCs altered embryo sensitivity and the expression of mRNA of a steroid receptor in the oocyte in a treatment and dose-dependent manner demonstrating that maternal EDC exposure in invertebrates may directly effect the embryos. A 'first-line-of-defense' mechanism present in many marine invertebrates is the multidrug resistance (MDR) transporter proteins which transport hydrophobic and conjugated compounds out of the cell. In sea stars, MDR transporters are expressed during oogenesis prior to oocyte maturation and an upregulation of MDR transport activity occurs during oocyte maturation. An increase in transport activity occurs during oocyte maturation and involves both permeability  glycoprotein (P-gp) and multidrug resistance-associated (MRP) transporters. The upregulation during maturation is initially due to a translocation of stored proteins to the oocyte cell membrane followed by translation of stored transporter mRNA. Expression of the transporters is not upregulated at fertilization in the sea star but there are changes in expression of the transporters after fertilization and during blastula formation and gastrulation. The inhibition of first cleavage in fertilized eggs by vinblastine is potentiated by specific inhibitors which also reduce first cleavage when used alone. The inhibition of cleavage suggests that MDR transporters may serve an important role in cell mitosis during early development. Several transcripts encoding MRP  transporters were identified using gene sequencing and eDNA macroarray technology including transcripts with homology to vertebrate MRPl, 5 and 8. In conclusion, these data demonstrate that marine invertebrates are sensitive to estrogenic compounds but do utilize defense mechanisms to ensure proper gametogenesis and embryonic development.

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