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重新思考非性腺组织的性别决定。

Rethinking sex determination of non-gonadal tissues.

机构信息

Department of Integrative Biology & Physiology, Laboratory of Neuroendocrinology of the Brain Research Institute, University of California, Los Angeles, CA, United States.

出版信息

Curr Top Dev Biol. 2019;134:289-315. doi: 10.1016/bs.ctdb.2019.01.003. Epub 2019 Feb 12.

Abstract

Evolution of genetic mechanisms of sex determination led to two processes causing sex differences in somatic phenotypes: gonadal differentiation and sex chromosome dosage inequality. In species with heteromorphic sex chromosomes, the sex of the individual is established at the time of formation of the zygote, leading to inherent sex differences in expression of sex chromosome genes beginning as soon as the embryonic transcriptome is activated. The inequality of sex chromosome gene expression causes sexual differentiation of the gonads and of non-gonadal tissues. The difference in gonad type in turn causes lifelong differences in gonadal hormones, which interact with unequal effects of X and Y genes acting within cells. Separating the effects of gonadal hormones and sex chromosomes has been possible using mouse models in which gonadal determination is separated from the sex chromosomes, allowing comparison of XX and XY mice with the same type of gonad. Sex differences caused by gonadal hormones and sex chromosomes affect basic physiology and disease mechanisms in most or all tissues.

摘要

性别决定的遗传机制的演变导致了两个导致躯体表型性别差异的过程

性腺分化和性染色体剂量不平衡。在具有异型性染色体的物种中,个体的性别在合子形成时就已经确定,这导致了性染色体基因的表达从胚胎转录组激活开始就存在内在的性别差异。性染色体基因表达的不平等导致了性腺和非性腺组织的性分化。性腺类型的差异反过来又导致了终生的性腺激素差异,这些差异与 X 和 Y 基因在细胞内的作用产生的不平等影响相互作用。通过使用性腺决定与性染色体分离的小鼠模型,已经可以分离性腺激素和性染色体的作用,从而可以比较具有相同类型性腺的 XX 和 XY 小鼠。性腺激素和性染色体引起的性别差异影响大多数或所有组织的基本生理和疾病机制。

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