The University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zatisi 728/II, 389 25, Vodnany, Czech Republic.
Department of Genetics, The Silberman Institute, The Hebrew University of Jerusalem, Jerusalem, Israel.
BMC Biol. 2024 Feb 16;22(1):39. doi: 10.1186/s12915-024-01842-z.
Surrogate production by germline stem cell transplantation is a powerful method to produce donor-derived gametes via a host, a practice known as surrogacy. The gametes produced by surrogates are often analysed on the basis of their morphology and species-specific genotyping, which enables conclusion to be drawn about the donor's characteristics. However, in-depth information, such as data on epigenetic changes, is rarely acquired. Germ cells develop in close contact with supporting somatic cells during gametogenesis in vertebrates, and we hypothesize that the recipient's gonadal environment may cause epigenetic changes in produced gametes and progeny. Here, we extensively characterize the DNA methylome of donor-derived sperm and their intergenerational effects in both inter- and intraspecific surrogates.
We found more than 3000 differentially methylated regions in both the sperm and progeny derived from inter- and intraspecific surrogates. Hypermethylation in the promoter regions of the protocadherin gamma gene in the intraspecific surrogates was found to be associated with germline transmission. On the contrary, gene expression level and the embryonic development of the offspring remained unaffected. We also discovered MAPK/p53 pathway disruption in interspecific surrogates due to promoter hypermethylation and identified that the inefficient removal of meiotic-arrested endogenous germ cells in hybrid gonads led to the production of infertile spermatozoa.
Donor-derived sperm and progeny from inter- and intraspecific surrogates were more globally hypermethylated than those of the donors. The observed changes in DNA methylation marks in the surrogates had no significant phenotypic effects in the offspring.
通过种系干细胞移植进行代孕生产是一种通过宿主产生供体来源配子的有效方法，这种做法被称为代孕。通过代孕产生的配子通常基于其形态和种属特异性基因分型进行分析，这可以得出关于供体特征的结论。然而，很少获得深入的信息，例如关于表观遗传变化的数据。在脊椎动物的配子发生过程中，生殖细胞与支持的体细胞密切接触，我们假设受体的性腺环境可能导致产生的配子和后代发生表观遗传变化。在这里，我们广泛描述了供体来源精子的 DNA 甲基化组及其在种间和种内代孕中的种间效应。
我们在种间和种内代孕的精子及其后代中发现了 3000 多个差异甲基化区域。在种内代孕中，原钙粘蛋白γ基因启动子区域的过度甲基化与种系传递有关。相反，后代的基因表达水平和胚胎发育不受影响。我们还发现由于启动子过度甲基化，种间代孕中的 MAPK/p53 途径被破坏，并确定杂交性腺中减数分裂停滞的内源性生殖细胞去除效率低下导致不育精子的产生。
种间和种内代孕的供体来源精子及其后代比供体的精子及其后代整体上甲基化程度更高。代孕中观察到的 DNA 甲基化标记变化对后代没有明显的表型影响。
