日本九州大学Katsuhiko Hayashi课题组在体外从雄性小鼠中产生功能性卵母细胞。相关论文于2023年3月15日在线发表在《自然》杂志上。

研究人员在小鼠多能干（PS）细胞中有效地将XY染色体组转换为XX染色体，而不需要额外的Y染色体。此外，这种染色体改变成功地根除了PS细胞中的16三体，即唐氏综合征的模型。人工生产的二倍体XX PS细胞在培养中分化为成熟的卵母细胞，其效率与原生XX PS细胞相似。利用这种方法，研究人员将来自性成熟雄性小鼠尾巴的诱导多能干细胞分化为完全有效的卵母细胞，并在受精后产生了子代。这项研究提供了一些见解，可以改善由性染色体或常染色体疾病引起的不孕症，并开启了双父本生殖的可能性。

研究人员表示，性染色体紊乱严重损害了男性和女性的配子发生。在卵子发生过程中，额外Y染色体的存在或X染色体的丢失会干扰卵母细胞的有力产生。

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

Source: https://www.nature.com/articles/s41586-023-05834-x