科學家在體外從雄性小鼠中產(chǎn)生功能性卵母細胞
2023.03.30
日本九州大學Katsuhiko Hayashi課題組在體外從雄性小鼠中產(chǎn)生功能性卵母細胞。相關(guān)論文于2023年3月15日在線發(fā)表在《自然》雜志上。
研究人員在小鼠多能干(PS)細胞中有效地將XY染色體組轉(zhuǎn)換為XX染色體,而不需要額外的Y染色體。此外,這種染色體改變成功地根除了PS細胞中的16三體,即唐氏綜合征的模型。人工生產(chǎn)的二倍體XX PS細胞在培養(yǎng)中分化為成熟的卵母細胞,其效率與原生XX PS細胞相似。利用這種方法,研究人員將來自性成熟雄性小鼠尾巴的誘導多能干細胞分化為完全有效的卵母細胞,并在受精后產(chǎn)生了子代。這項研究提供了一些見解,可以改善由性染色體或常染色體疾病引起的不孕癥,并開啟了雙父本生殖的可能性。
研究人員表示,性染色體紊亂嚴重損害了男性和女性的配子發(fā)生。在卵子發(fā)生過程中,額外Y染色體的存在或X染色體的丟失會干擾卵母細胞的有力產(chǎn)生。
附:英文原文
Title: Generation of functional oocytes from male mice in vitro
Author: Murakami, Kenta, Hamazaki, Nobuhiko, Hamada, Norio, Nagamatsu, Go, Okamoto, Ikuhiro, Ohta, Hiroshi, Nosaka, Yoshiaki, Ishikura, Yukiko, Kitajima, Tomoya S., Semba, Yuichiro, Kunisaki, Yuya, Arai, Fumio, Akashi, Koichi, Saitou, Mitinori, Kato, Kiyoko, Hayashi, Katsuhiko
Issue&Volume: 2023-03-15
Abstract: Sex chromosome disorders severely compromise gametogenesis in both males and females. In oogenesis, the presence of an additional Y chromosome or the loss of an X chromosome disturbs the robust production of oocytes1,2,3,4,5. Here we efficiently converted the XY chromosome set to XX without an additional Y chromosome in mouse pluripotent stem (PS) cells. In addition, this chromosomal alteration successfully eradicated trisomy 16, a model of Down’s syndrome, in PS cells. Artificially produced euploid XX PS cells differentiated into mature oocytes in culture with similar efficiency to native XX PS cells. Using this method, we differentiated induced pluripotent stem cells from the tail of a sexually mature male mouse into fully potent oocytes, which gave rise to offspring after fertilization. This study provides insights that could ameliorate infertility caused by sex chromosome or autosomal disorders, and opens the possibility of bipaternal reproduction.
DOI: 10.1038/s41586-023-05834-x