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TRIM28 依赖性 SUMOylation 保护成年卵巢免受睾丸途径的激活。

TRIM28-dependent SUMOylation protects the adult ovary from activation of the testicular pathway.

机构信息

Institute of Human Genetics, CNRS UMR9002 University of Montpellier, 34396, Montpellier, France.

Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France.

出版信息

Nat Commun. 2022 Jul 29;13(1):4412. doi: 10.1038/s41467-022-32061-1.

DOI:10.1038/s41467-022-32061-1
PMID:35906245
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9338040/
Abstract

Gonadal sexual fate in mammals is determined during embryonic development and must be actively maintained in adulthood. In the mouse ovary, oestrogen receptors and FOXL2 protect ovarian granulosa cells from transdifferentiation into Sertoli cells, their testicular counterpart. However, the mechanism underlying their protective effect is unknown. Here, we show that TRIM28 is required to prevent female-to-male sex reversal of the mouse ovary after birth. We found that upon loss of Trim28, ovarian granulosa cells transdifferentiate to Sertoli cells through an intermediate cell type, different from gonadal embryonic progenitors. TRIM28 is recruited on chromatin in the proximity of FOXL2 to maintain the ovarian pathway and to repress testicular-specific genes. The role of TRIM28 in ovarian maintenance depends on its E3-SUMO ligase activity that regulates the sex-specific SUMOylation profile of ovarian-specific genes. Our study identifies TRIM28 as a key factor in protecting the adult ovary from the testicular pathway.

摘要

哺乳动物的性腺性别命运在胚胎发育过程中就已确定，并且在成年后必须积极维持。在小鼠卵巢中，雌激素受体和 FOXL2 可保护卵巢颗粒细胞免于向睾丸对应的 Sertoli 细胞转分化。然而，其保护作用的机制尚不清楚。本研究表明，TRIM28 是防止小鼠出生后卵巢雌性到雄性性别逆转所必需的。研究发现，在 Trim28 缺失的情况下，卵巢颗粒细胞通过不同于性腺胚胎祖细胞的中间细胞类型转分化为 Sertoli 细胞。TRIM28 被募集到 FOXL2 附近的染色质上，以维持卵巢途径并抑制睾丸特异性基因。TRIM28 在卵巢维持中的作用取决于其 E3-SUMO 连接酶活性，该活性调节卵巢特异性基因的性别特异性 SUMO 化谱。本研究确定 TRIM28 是保护成年卵巢免受睾丸途径影响的关键因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63e8/9338040/70217ca8d2df/41467_2022_32061_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63e8/9338040/f197be542511/41467_2022_32061_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63e8/9338040/2cac1fd699db/41467_2022_32061_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63e8/9338040/4a37c7d39ac6/41467_2022_32061_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63e8/9338040/4417b062a9ee/41467_2022_32061_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63e8/9338040/70217ca8d2df/41467_2022_32061_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63e8/9338040/f197be542511/41467_2022_32061_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63e8/9338040/42c57d4ab06d/41467_2022_32061_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63e8/9338040/2cac1fd699db/41467_2022_32061_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63e8/9338040/4a37c7d39ac6/41467_2022_32061_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63e8/9338040/4417b062a9ee/41467_2022_32061_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63e8/9338040/70217ca8d2df/41467_2022_32061_Fig6_HTML.jpg

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Adv Sci (Weinh). 2025 Aug;12(30):e01973. doi: 10.1002/advs.202501973. Epub 2025 Jun 10.
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