Embryonic regulation of the endocrine environment via the sulfotransferase-sulfatase pathway in an oviparous vertebrate

胚胎发育过程中的内分泌信号调节许多生理过程，并可产生长期影响，可能持续整个生物体的一生。例如，胚胎可以暴露于母体产生的类固醇激素。在哺乳动物中，包括人类，胎盘产生代谢酶，使母体类固醇在到达发育中的胚胎之前失去活性。因此，胚胎被缓冲免受母体类固醇的潜在有害影响。在产卵的物种中，胚胎在产卵时暴露于存在于蛋黄中的母体类固醇。这个项目研究了雌激素是如何从海龟的蛋黄转移到胚胎的。此外，将采用各种分子和生物化学技术来表征这些母体类固醇在胚胎发育过程中的代谢。拟议的研究将增强我们对胚胎如何调节内分泌环境的了解。重要的是，许多相同的代谢酶检查在这个建议也负责代谢外源性化学品，如增塑剂和农药。表征这些酶将使研究人员能够调查这些外来化学物质是否会破坏类固醇代谢产生有害影响。与那些从活轴承的物种相比，从产卵物种的胚胎提供了一个强大的系统，在其中研究各种因素如何影响胚胎类固醇代谢，因为它们在母体环境之外发展，可以很容易地操纵。本提案中的所有实验将为研究生和本科生以及博士后研究人员提供培训机会。

Endocrine signaling during embryonic development regulates many physiological processes and can produce long-term effects that may persist throughout the lifetime of an organism. For example, the embryo may be exposed to steroid hormones produced by the mother. In mammals, including humans, the placenta produces enzymes that metabolize, and render inactive, maternal steroids before they reach the developing embryo. Thus, the embryo is buffered from the potentially detrimental effects of maternal steroids. In species that lay eggs, embryos are exposed to maternal steroids present in the yolk when the egg is laid. This project examines how maternal steroids move from the yolk to the embryo in turtles. In addition, a variety of molecular and biochemical techniques will be employed to characterize how these maternal steroids are metabolized during embryonic development. The proposed research will enhance our understanding of how embryos regulate their endocrine environment. Importantly, many of the same metabolic enzymes examined in this proposal are also responsible for metabolizing exogenous chemicals such as plasticizers and pesticides. Characterizing these enzymes will enable researchers to investigate whether these foreign chemicals may disrupt steroid metabolism to produce detrimental effects. Compared to those from live-bearing species, embryos from egg-laying species provide a powerful system in which to study how various factors influence embryonic steroid metabolism because they develop outside of the maternal environment and can be readily manipulated. All experiments in this proposal will provide training opportunities to both graduate and undergraduate students, as well as a post-doctoral researcher.