Wei Yanchang, Yue Tao, Wang Yuanyuan, Yang Yan
Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China.
Proc Natl Acad Sci U S A. 2025 Jul 8;122(27):e2425307122. doi: 10.1073/pnas.2425307122. Epub 2025 Jun 23.
Each new mammalian life begins with the fusion of an oocyte and a sperm to produce a fertilized egg containing two sets of genomes, one from the mother and one from the father. Androgenesis, a way for producing offspring solely from male genetic material, is limited in mammals, presumably due to barriers arising from genomic imprinting, an epigenetic mechanism leading to monoallelic gene expression. Here, we report adult mammalian offspring derived from the genetic material of two sperm cells. These mice, which we refer to as androgenetic mice, were produced via targeted DNA methylation editing of seven imprinting control regions (ICRs) through CRISPR-based epigenome engineering. Two sperm cells were injected into an enucleated oocyte to form putatively diploid embryos. Allele-specific epigenetic editing was achieved by injecting guide RNAs with protospacer adjacent motif (PAM) sequences designed to match one allele but not the other. The birth of androgenetic mice that were able to develop to adulthood demonstrates that mammalian androgenesis is achievable by targeted epigenetic remodeling of a few defined ICRs.
每一个新的哺乳动物生命都始于一个卵母细胞和一个精子的融合，从而产生一个受精卵，其中包含两组基因组，一组来自母亲，一组来自父亲。孤雄生殖是一种仅利用雄性遗传物质产生后代的方式，在哺乳动物中受到限制，这可能是由于基因组印记所产生的障碍，基因组印记是一种导致单等位基因表达的表观遗传机制。在此，我们报告了源自两个精子细胞遗传物质的成年哺乳动物后代。这些小鼠，我们称之为孤雄生殖小鼠，是通过基于CRISPR的表观基因组工程对七个印记控制区域（ICR）进行靶向DNA甲基化编辑而产生的。将两个精子细胞注入去核卵母细胞中以形成假定的二倍体胚胎。通过注射具有与一个等位基因而非另一个等位基因匹配的原间隔序列临近基序（PAM）的引导RNA，实现了等位基因特异性表观遗传编辑。能够发育到成年的孤雄生殖小鼠的诞生表明，通过对一些特定的ICR进行靶向表观遗传重塑，可以实现哺乳动物的孤雄生殖。
