Generation of functional oocytes from male mice in vitro

Generation of functional oocytes from male mice in vitro

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 oocytes(1-5). 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.

性染色体疾病严重损害雄性和雌性的配子发生。在卵子发生过程中，额外Y染色体的存在或X染色体的缺失会干扰卵母细胞的稳定产生（1 - 5）。在此，我们在小鼠多能干细胞（PS细胞）中有效地将XY染色体组转变为无额外Y染色体的XX染色体组。此外，这种染色体改变成功地消除了PS细胞中的16三体（唐氏综合征的一种模型）。人工产生的整倍体XX PS细胞在培养中分化为成熟卵母细胞的效率与天然XX PS细胞相似。利用这种方法，我们将性成熟雄性小鼠尾巴的诱导多能干细胞分化为完全有功能的卵母细胞，这些卵母细胞受精后产生了后代。这项研究为改善由性染色体或常染色体疾病导致的不育提供了思路，并开启了双父本生殖的可能性。