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，并可产生可能持续整个生物体一生的长期影响。例如，胚胎可能会接触到母亲产生的类固醇激素。在包括人类在内的哺乳动物中，胎盘产生的酶在母体类固醇到达发育中的胚胎之前代谢并使其失去活性。因此，胚胎可以免受母体类固醇的潜在有害影响。在产卵的物种中，当产卵时，胚胎暴露在蛋黄中的母体类固醇中。这个项目研究了母体类固醇是如何从海龟的卵黄转移到胚胎的。此外，还将使用各种分子和生化技术来表征这些母体类固醇在胚胎发育期间如何代谢。这项拟议的研究将加深我们对胚胎如何调节其内分泌环境的理解。重要的是，该提案中研究的许多相同的代谢酶也负责代谢外源化学物质，如增塑剂和杀虫剂。对这些酶进行表征将使研究人员能够调查这些外来化学物质是否会扰乱类固醇新陈代谢，从而产生有害影响。与活的生育物种的胚胎相比，产卵物种的胚胎提供了一个强大的系统来研究各种因素是如何影响胚胎类固醇代谢的，因为它们在母体环境之外发育，并且很容易被操纵。该提案中的所有实验都将为研究生和本科生以及博士后研究员提供培训机会。

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.