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cyp11a1突变型XX罗非鱼中类固醇激素缺乏导致的性逆转在分子水平经历了类似卵巢的阶段。

Steroid hormone-deprived sex reversal in cyp11a1 mutant XX tilapia experiences an ovary-like stage at molecular level.

作者信息

Xiao Hesheng, Wang Leihui, Yan Shuo, Ma He, Xu Zhen, Wang Feilong, Wang Jingrong, Tao Wenjing, Wang Deshou

机构信息

Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Sciences, Southwest University, Chongqing, 400715, China.

出版信息

Commun Biol. 2024 Sep 16;7(1):1154. doi: 10.1038/s42003-024-06853-8.

DOI:10.1038/s42003-024-06853-8
PMID:39284885
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11405705/
Abstract

Fish sex is largely influenced by steroid hormones, especially sex hormones. Here, we established a steroid hormone-free genetic model by mutation of cyp11a1 in Nile tilapia, which was confirmed by EIA assay. Gonadal phenotype and transcriptome analyses showed that the XX mutants displayed sex reversal from female to male but with defective spermatogenesis. Despite the sex reversal, the aromatase encoding gene cyp19a1a was continuously expressed in the gonads of the XX mutants, which might be caused by androgen deficiency. Whole-mount fluorescence in situ hybridization and transcriptome analysis showed that the gonads of the XX mutants firstly developed towards ovary but shifted to testis between 10 to 15 days after hatching. Detailed expression analysis of key sex differentiation pathway genes foxl3 and dmrt1 combined with apoptosis analysis revealed transdifferentiation of germ cells from female to male during sex reversal. Rescue experiments showed that both P5 and E2 treatment rescued the sex reversal of cyp11a1 mutant XX fish. Overall, our results revealed a transient ovary-like stage and transdifferentiation of germ cells from female to male in the early gonads of the steroid hormone-deprived cyp11a1 mutant XX fish.

摘要

鱼类的性别很大程度上受类固醇激素尤其是性激素的影响。在此，我们通过尼罗罗非鱼中cyp11a1基因的突变建立了一个无类固醇激素的遗传模型，这通过酶免疫分析得以证实。性腺表型和转录组分析表明，XX突变体表现出从雌性到雄性的性逆转，但精子发生存在缺陷。尽管发生了性逆转，但编码芳香化酶的基因cyp19a1a在XX突变体的性腺中持续表达，这可能是由雄激素缺乏导致的。全组织荧光原位杂交和转录组分析表明，XX突变体的性腺最初向卵巢发育，但在孵化后10至15天之间转变为睾丸。对关键性别分化途径基因foxl3和dmrt1的详细表达分析结合凋亡分析揭示了性逆转过程中生殖细胞从雌性向雄性的转分化。拯救实验表明，P5和E2处理均挽救了cyp11a1突变体XX鱼的性逆转。总体而言，我们的结果揭示了在缺乏类固醇激素的cyp11a1突变体XX鱼早期性腺中存在一个短暂的卵巢样阶段以及生殖细胞从雌性向雄性的转分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80c1/11405705/5a9c8461365d/42003_2024_6853_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80c1/11405705/f3019cce4cfc/42003_2024_6853_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80c1/11405705/de387d66024a/42003_2024_6853_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80c1/11405705/0840d80bcfbe/42003_2024_6853_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80c1/11405705/46dc75f22bb1/42003_2024_6853_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80c1/11405705/3a5b89d544a7/42003_2024_6853_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80c1/11405705/623defee67cc/42003_2024_6853_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80c1/11405705/c116bfadb3e0/42003_2024_6853_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80c1/11405705/5a9c8461365d/42003_2024_6853_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80c1/11405705/f3019cce4cfc/42003_2024_6853_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80c1/11405705/de387d66024a/42003_2024_6853_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80c1/11405705/0840d80bcfbe/42003_2024_6853_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80c1/11405705/46dc75f22bb1/42003_2024_6853_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80c1/11405705/3a5b89d544a7/42003_2024_6853_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80c1/11405705/623defee67cc/42003_2024_6853_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80c1/11405705/c116bfadb3e0/42003_2024_6853_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80c1/11405705/5a9c8461365d/42003_2024_6853_Fig8_HTML.jpg

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Nat Commun. 2023 Mar 14;14(1):1428. doi: 10.1038/s41467-023-37026-6.
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Endocrinology. 2022 Feb 1;163(2). doi: 10.1210/endocr/bqab258.
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Cyp17a1 is Required for Female Sex Determination and Male Fertility by Regulating Sex Steroid Biosynthesis in Fish.
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Endocrinology. 2021 Dec 1;162(12). doi: 10.1210/endocr/bqab205.
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Gen Comp Endocrinol. 2021 Nov 1;313:113893. doi: 10.1016/j.ygcen.2021.113893. Epub 2021 Aug 27.
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Development. 2021 Apr 15;148(8). doi: 10.1242/dev.199380. Epub 2021 Apr 20.
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