註釋 This dissertation used a rat model to investigate the mechanisms behind the effects of primary and secondary zinc deficiency during pregnancy. The first chapter reviewed previous research that led to the hypothesis that marginal zinc deficiency disrupts ERK1/2 signaling leading to an impairment of fetal brain development. The second chapter used a rat model together with cell culture experiments to test the hypothesis that disruption of ERK signaling resulting from zinc deficiency leads to decreased neural progenitor cell proliferation. Results of this study suggested that zinc deficiency impaired the ERK1/2 signaling pathway leading to a decreased rate of neural progenitor cell proliferation through a mechanism involving activation of the ERK- directed phosphatase PP2A. Chapter three investigated the hypothesis that disruption of ERK1/2 signaling and NPC proliferation resulting from marginal zinc deficiency disrupts neurogenesis in the frontal cortex of the fetal rat brain. Results from this study suggest that disruption of ERK signaling resulting from marginal zinc deficiency led to an impairment of fetal neurogenesis. Disruption of fetal neurogenesis following marginal zinc deficiency during pregnancy resulted in decreased neuronal density in the mature frontal cortex of the rat brain following postnatal repletion with adequate zinc levels. Therefore, cortical malformations resulting from marginal zinc deficiency may contribute to the persistent effects on behavior following repletion with adequate dietary zinc levels. The fourth chapter covers previous literature on primary and secondary zinc deficiency during pregnancy. While preterm birth was identified as a major obstetric complication resulting from primary zinc deficiency, exposure to toxicants that induce secondary zinc deficiency during pregnancy was identified as a risk factor for preterm birth. In particular, maternal exposure to the endocrine disrupting phthalate plasticizer DEHP was highlighted as a risk factor for preterm birth that may act at least in part through the mechanism of a hepatic acute-phase response leading to secondary zinc deficiency. The fifth chapter investigated the interaction between maternal exposure to DEHP and marginal zinc deficiency to affect the hepatic acute-phase response, zinc homeostasis, and steroid hormone metabolism. Maternal DEHP exposure decreased maternal weight gain and led to zinc accumulation in liver of dams fed a diet containing an adequate level of zinc and this was associated with a hepatic acute-phase response. DEHP and marginal zinc deficiency caused several adverse effects on the maternal and fetal steroid profiles. There were interactions between DEHP exposure and marginal zinc nutrition, as well as effects specifically related to DEHP or marginal zinc deficiency. Together these studies stress the importance of adequate dietary zinc intake during pregnancy to support development of the nervous and endocrine systems. 