Project description:Folliculogenesis in mammals is a cyclic and hierarchical process that the ovarian follicles undergo dramatic changes in the shape and number of granulosa cells accompanied by gradually enlarged immature oocyte. Here we show a thorough and high-resolution view of DNA methylation maps in oocyte free of somatic cells present at each distinct follicular development stages. We found that global DNA establishment occurs in Type5b follicles, the final stage of pre-antral follicles, and that the acquisition of DNA methylation at different trans-regulatory elements couples with different chromatin modifiers. Besides, we showed that Dnmt1 as well as Uhrf1 also play critical roles in requiring and retaining of de novo methylation statue, typically at LINE and LTR elements, in these immature oocytes, which successfully escape DNA replication. Our study thus refined the current knowledge on the establishment of unique DNA methylation profile in mammalian oocytes, and provide a valuable resource for further studies on female gametogenesis.
Project description:Folliculogenesis in mammals is a cyclic and hierarchical process that the ovarian follicles undergo dramatic changes in the shape and number of granulosa cells accompanied by gradually enlarged immature oocyte. Here we show a thorough and high-resolution view of DNA methylation maps in oocyte free of somatic cells present at each distinct follicular development stages. We found that global DNA establishment occurs in Type5b follicles, the final stage of pre-antral follicles, and that the acquisition of DNA methylation at different trans-regulatory elements couples with different chromatin modifiers. Besides, we showed that Dnmt1 as well as Uhrf1 also play critical roles in requiring and retaining of de novo methylation statue, typically at LINE and LTR elements, in these immature oocytes, which successfully escape DNA replication. Our study thus refined the current knowledge on the establishment of unique DNA methylation profile in mammalian oocytes, and provide a valuable resource for further studies on female gametogenesis.
Project description:Folliculogenesis in mammals is a cyclic and hierarchical process that the ovarian follicles undergo dramatic changes in the shape and number of granulosa cells accompanied by gradually enlarged immature oocyte. Here we show a thorough and high-resolution view of DNA methylation maps in oocyte free of somatic cells present at each distinct follicular development stages. We found that global DNA establishment occurs in Type5b follicles, the final stage of pre-antral follicles, and that the acquisition of DNA methylation at different trans-regulatory elements couples with different chromatin modifiers. Besides, we showed that Dnmt1 as well as Uhrf1 also play critical roles in requiring and retaining of de novo methylation statue, typically at LINE and LTR elements, in these immature oocytes, which successfully escape DNA replication. Our study thus refined the current knowledge on the establishment of unique DNA methylation profile in mammalian oocytes, and provide a valuable resource for further studies on female gametogenesis.
Project description:The factors and processes involved in primate follicular development are complex and not fully understood. An encapsulated three-dimensional (3D) follicle culture system could be a valuable in vitro model to study the dynamics and regulation of folliculogenesis in intact individual follicles in primates. Besides the research relevance, in vitro follicle maturation (IFM) is emerging as a promising approach to offer options for fertility preservation in female patients with cancer. This review summarizes the current published data on in vitro follicular development from the preantral to small antral stage in nonhuman primates, including follicle survival and growth, endocrine (ovarian steroid hormone) and paracrine/autocrine (local factor) function, as well as oocyte maturation and fertilization. Future directions include major challenges and strategies to further improve follicular growth and differentiation with oocytes competent for in vitro fertilization and subsequent embryonic development, as well as opportunities to investigate primate folliculogenesis by utilizing this 3D culture system. The information may be valuable in identifying optimal conditions for human follicle culture, with the ultimate goal of translating the experimental results and products to patients, thereby facilitating diagnostic and therapeutic approaches for female fertility.
Project description:The establishment of DNA methylation patterns in oocytes is a highly dynamic process marking gene-regulatory events during fertilization, embryonic development, and adulthood. However, after epigenetic reprogramming in primordial germ cells, how and when DNA methylation is re-established in developing human oocytes remains to be characterized. Here, using single-cell whole-genome bisulfite sequencing, we describe DNA methylation patterns in three different maturation stages of human oocytes. We found that while broad-scale patterns of CpG methylation have been largely established by the immature germinal vesicle stage, localized changes continue into later development. Non-CpG methylation, on the other hand, undergoes a large-scale, generalized remodeling through the final stage of maturation, with the net overall result being the accumulation of methylation as oocytes mature. The role of the genome-wide, non-CpG methylation remodeling in the final stage of oocyte maturation deserves further investigation.
