Department of Marine Biology, Texas A&M University at Galveston, Galveston, TX, USA.
Syst Biol Reprod Med. 2023 Aug;69(4):271-287. doi: 10.1080/19396368.2023.2188996. Epub 2023 Apr 6.
Vertebrate sex determination and differentiation are coordinated by the activations and maintenance of reproductive transcriptional-regulatory networks (TRNs). There is considerable interest in studying the conserved design principles and functions of reproductive TRNs given that their intricate regulation is susceptible to disruption by gene mutations or exposures to exogenous endocrine disrupting chemicals (or EDCs). In this manuscript, the Boolean rules describing reproductive TRNs in humans, mice, and zebrafish, were represented as a pseudo-stoichiometric matrix model. This model mathematically described the interactions of 35 transcription factors with 21 sex determination and differentiation genes across the three species. The approach of Extreme Pathway (ExPa) analysis was used to predict the extent of TRN gene activations subject to the species-specific transcriptomics data, from across various developmental life-stages. A goal of this work was to identify conserved and functional reproductive TRNs across the three species. ExPa analyses predicted the sex differentiation genes, DHH, DMRT1, and AR, to be highly active in male humans, mice, and zebrafish. Whereas FOXL2 was the most active gene in female humans and mice; and CYP19A1A in female zebrafish. These results agree with the expectation that regardless of a lack of sex determination genes in zebrafish, the TRNs responsible for canalizing male female sexual differentiation are conserved with mammalian taxa. ExPa analysis therefore provides a framework with which to study the TRNs that influence the development of sexual phenotypes. And the predicted conservation of sex differentiation TRNs between mammals and zebrafish identifies the piscine species as an effective model to study mammalian reproductive systems under normal or perturbed pathologies.
脊椎动物的性别决定和分化是由生殖转录调控网络（TRN）的激活和维持协调的。鉴于生殖 TRN 的复杂调节容易受到基因突变或外源性内分泌干扰化学物质（或 EDCs）的影响，因此研究其保守的设计原则和功能引起了相当大的兴趣。在本文中，描述人类、小鼠和斑马鱼生殖 TRN 的布尔规则表示为伪化学计量矩阵模型。该模型从三个物种的各种发育生命阶段的转录组学数据中，数学描述了 35 个转录因子与 21 个性别决定和分化基因之间的相互作用。极端途径（ExPa）分析方法用于预测 TRN 基因激活的程度，这取决于物种特异性的转录组学数据。这项工作的目标之一是确定三个物种之间保守和功能的生殖 TRN。ExPa 分析预测性别分化基因 DHH、DMRT1 和 AR 在男性人类、小鼠和斑马鱼中高度活跃。而 FOXL2 是女性人类和小鼠中最活跃的基因；而 CYP19A1A 在雌性斑马鱼中最活跃。这些结果与预期一致，即无论斑马鱼缺乏性别决定基因，负责将雄性和雌性性分化渠道化的 TRN 与哺乳动物类群是保守的。因此，ExPa 分析为研究影响性表型发育的 TRN 提供了一个框架。并且哺乳动物和斑马鱼之间性别分化 TRN 的预测保守性确定了鱼类物种是研究正常或病理扰动下哺乳动物生殖系统的有效模型。
