动物的性别决定基因及其甲基化调控的研究进展

doi:10.11843/j.issn.0366-6964.2025.09.001

摘要/Abstract

摘要：

动物的性别决定(sex determination)是有性繁殖动物在性别发生分化后分别发育为雌性或雄性个体且出现形态和生理差异的现象。动物的性别决定分为环境型和遗传型。目前已查明一些基因在动物性别决定中扮演重要角色。动物的性别决定还与DNA的甲基化密不可分，比如哺乳动物X染色体的全域DNA甲基化。然而，DNA甲基化在不同物种性别决定中的作用却存在着显著的差异。本文对动物性别决定的影响因素和关键基因以及基因的DNA甲基化与不同物种性别决定的关联进行综述，为进一步研究动物性别决定机制提供有益参考。

关键词: DNA甲基化, 性别决定, 动物, 差异表达基因, 表观遗传调控

Abstract:

Sex determination in the sexually reproducing animals refers to the phenomenon in which the animals develop into female or male individuals and exhibit morphological and physiological differences after gender differentiation. Sex determination in animals is divided into environmental and genetic types. Currently, it has been identified that some genes play important roles in animal sex determination. The sex determination of animals is also closely related to DNA methylation, such as the global DNA methylation of mammalian X chromosome. However, the role of DNA methylation in sex determination varies significantly among different animal species. This article reviews the influencing factors and key genes of animal sex determination, as well as the association between DNA methylation of genes and sex determination in different species, which provides useful references for further research on the mechanism of animal sex determination.

Key words: DNA methylation, sex determination, animal, differentially expressed genes, epigenetic regulation

中图分类号:

S183.2

林晓, 李瑞杰, 刘龙, 耿拓宇, 龚道清. 动物的性别决定基因及其甲基化调控的研究进展[J]. 畜牧兽医学报, 2025, 56(9): 4129-4142.

LIN Xiao, LI Ruijie, LIU Long, GENG Tuoyu, GONG Daoqing. Research Progress on Sex Determining Genes and Their Methylation Regulation in Animals[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(9): 4129-4142.

图/表 4

表 1

图 1

图 2

表 2

DNA甲基化在动物性别决定中的作用"

动物分类 Classification of animals	物种 Animal species	基因 Gene	科学证据 Scientific evidence	文献 Reference
哺乳动物 Mammal	小鼠	SRY	在E11.5胚胎中，SRY开始表达，SRY上游CpG位点会发生性腺特异性的低甲基化；在E15.5胚胎中，SRY上游CpG位点又恢复到高甲基化状态而使其表达停止	[54]
哺乳动物 Mammal	小鼠	GADD45G	GADD45G基因被敲除后，其性别会从雄性转变为雌性，这可能与GADD45G基因诱导SRY基因的DNA去甲基化有关	[55]
鸟类 Bird	鸡	MHM	MHM区域附近的雌性基因的表达量显著高于雄性，雄性性腺的MHM甲基化水平高于雌性	[62]
爬行动物 Reptile	海龟	AMH、AR、GATA4、LHX9和SF1	在雄性中表达量升高可能是雌性中这些基因启动子甲基化导致的，它们影响卵巢形成，并且在雄性中被甲基化	[64、65]
	美洲鳄	CYP19A1	与在FPT下孵育相比，MPT孵化的胚胎中性腺的CYP19A1基因启动子甲基化水平较高，基因表达水平降低	[67]
	美洲鳄	SOX9	与MPT相比，FPT孵育导致SOX9基因启动子甲基化增加，胚胎性腺中表达量减少	[67]
	红耳龟	DMRT1	MPT性腺中DMRT1基因启动子中CpG甲基化的水平显著低于FPT性腺中DMRT1基因启动子中CpG甲基化的水平	[26、68]
	红耳龟	CYPl9A1	CYP19A1基因的启动子区域CpG位点的DNA甲基化水平随着温度的变化而变化	[68]
	短吻鳄	CYP19A1和SOX9	MPT下性腺中CYP19A1基因启动子甲基化升高，且相对于在FPT的基因表达水平降低，SOX9基因在雌性胚胎的性腺中的DNA甲基化水平高于雄性	[67]
两栖动物 Batrachians	中国大鲵	LHX9和CYP19A1	四个CpG位点在睾丸中的甲基化水平显著高于卵巢，且与LHX9基因的表达呈负相关； CpG甲基化水平与发育中的卵巢的CYP19A1基因的表达呈负相关	[69]
鱼类 Pisces	硬骨鱼	CYP19A1和DMRT1	近端启动子和第一外显子的DNA甲基化水平在睾丸和卵巢之间存在差异	[70]
	欧洲鲈鱼	CYP19A	雄性性腺的CYP19A基因启动子处的DNA甲基化水平是雌性的两倍，随着温度的升高，CYP19A基因启动子的DNA甲基化水平也增加	[72]
	黑鲷	CYP19A1	CYP19A1基因的启动子会逐渐去甲基化，这与其卵巢发育有关	[73]
	尖吻鲈	CYP19A1、AMH、DMRT1和NR5A2	雄性个体CYP19A1和AMH基因的甲基化水平比雌性高，而雌性中DMRT1和NR5A2基因的甲基化水平比雄性高	[77]
	尼罗罗非鱼	CYP19A1A	早期发育阶段经历高温会增加CYP19A1A基因启动子的DNA甲基化水平，这与CYP19A1A基因的mRNA表达水平升高相一致	[78]
	翘嘴鲌鱼	DMRT1	DMRT1基因的启动子CpG在睾丸中未甲基化，而在卵巢中高度甲基化	[79]
	舌鳎	AMH	AMH基因在雄性中的表达量高于雌性，且AMH基因的表达与DNA甲基化有关	[80]

表 2

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动物分类 Classification of animals	物种 Animal species	基因 Gene	科学证据 Scientific evidence	文献 Reference
哺乳动物 Mammal	小鼠	SRY	在正调控因子的作用下，SRY基因在未分化性腺体细胞中开始表达，诱导未分化性腺向雄性分化，SRY基因表达后激活其下游靶基因SOX9的表达，使性腺向睾丸分化	[17、18]
鸟类 Bird	鸡	DMRT1	敲除DMRT1基因会导致雄性鸡胚的左侧性腺发生雌性化	[20]
爬行动物 Reptile	中华鳖	CYP19A1	使用FAD处理以及敲低雌性胚胎的CYP19A1基因后，其性别逆转为雄性	[25]
两栖类 Batrachians	粗皮蛙	DMRT1	向雌性注射睾酮，促使其发生性逆转，且在性逆转雄性的性腺中，DMRT1基因的表达上调	[41]
两栖类 Batrachians	非洲瓜蟾	DM-W	DM-W基因抑制DMRT1基因的表达(可使胚胎雄性化)，并上调CYP19A1和FOXL2基因的表达	[43]
鱼类 Pisces	青鳉	SOX3	SOX3基因在雌性中过表达或在雄性中敲除都会导致性反转	[38]
	虹鳟	CYP19A1	FAD阻断雌激素的合成，诱导精巢的产生	[44、45]
	斜带石斑鱼	SOX9	SOX9基因的高表达诱导雌性向雄性转化	[37]
	斑马鱼	CYP19A1	敲除CYP19A1基因会导致其发生性反转	[44、45]
	斑马鱼	AMH	敲除AMH基因后，性别比例偏雌性，且雄雌性均发育出肥厚的性腺	[39、40]
	尼罗罗非鱼	GSDF	雌性GSDF基因过表达会导致其转变为功能性雄鱼，敲除雄性GSDF基因会导致其向雌鱼的性反转	[38、41]
	尼罗罗非鱼	DMRT1	雌性中过表达DMRT1基因会导致后卵巢腔发育迟缓，卵泡退化，部分鱼类出现完全性反转	[42、43]

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