Generation of ovarian follicles from mouse pluripotent stem cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE151143 | GEO | 2021/07/16
REPOSITORIES: GEO
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Project description:A major technology for generating oocytes by in vitro gametogenesis involves generating ovary models called reconstituted ovaries (rOvaries). Widespread use of rOvaries depends on the reliable manufacturing of primordial germ cell like cells (PGCLCs) and fetal ovarian somatic cells (FOSCs). Using scRNA-seq, we identify that upon thaw, FOSCs are composed largely of Foxl2+ pre-granulosa cells, KRT19+ epithelial cells and Nr2f2+ mesenchymal cells which self-assemble together with PGCLCs into disc-like organoids containing multiple follicles embedded in NR2F2 stroma without an ovarian surface epithelium and no steroidogenic theca. The absence of an ovarian surface epithelium combined with the small size of GV-oocytes indicates that follicle production in the rOvary corresponds to first-wave folliculogenesis.
2023-12-14 | GSE238263 | GEO
Project description:Reconstitution of female germ-cell development in vitro is a key challenge in reproductive biology and medicine. We show here that female (XX) embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in mice are induced into primordial germ cell-like cells (PGCLCs), which, when aggregated with female gonadal somatic cells as reconstituted ovaries, develop pre-meiotic germ cell characteristics, including X-reactivation, imprint erasure, and cyst formation. Upon transplantation under ovarian bursa, PGCLCs in the reconstituted ovaries mature into germinal vesicle-stage oocytes, which, through in vitro maturation and fertilization, contribute to fertile offspring. Our culture system serves as a robust foundation for the investigation of key properties of female germ cells, including the acquisition of totipotency, and for the reconstitution of whole female germ-cell development in vitro. We performed expression analysis of female PGC-like cells [PGCLCs; day 3 (d3), day 6 (d6), and day 3 followed by day 6 in aggregation with female embryonic day (E) 12.5 gonadal somatic cells (d3ag6)] in comparison to in vivo embryonic PGCs (E12.5 female PGCs and E9.5 PGCs) and male d6 PGCLCs. PGCLCs were marked with fluorescence of Blimp1-mVenus, stella-ECFP transgenic reporters (BVSC). PGCs were marked with fluorescence of the stella-EGFP transgenic reporter.
2012-11-05 | E-GEOD-40716 | biostudies-arrayexpress
Project description:Understanding the unique mechanisms of human oogenesis necessitates the development of an in vitro system of stem cell differentiation into oocytes. Specialized cell types and organoids have been derived from human pluripotent stem cells in vitro, but generating a human ovarian follicle remains a challenge. Here we report that human embryonic stem cells (hESCs) can be induced to differentiate into ovarian follicle-like cells in vitro. First, we find that two RNA-binding proteins specifically expressed in germ cells, DAZL and BOULE, regulate the exit from pluripotency and entry into meiosis. By expressing DAZL and BOULE with recombinant human GDF9 and BMP15, these meiotic germ cells are further induced to form ovarian follicle-like cells (FLCs), including oocytes and granulosa cells. This robust in vitro differentiation system will allow the study of the unique molecular mechanisms underlying human pluripotent stem cell differentiation into late PGCs, meiotic germ cells, and ovarian follicles.
2017-07-04 | GSE97388 | GEO
Project description:Reconstitution of female germ-cell development in vitro is a key challenge in reproductive biology and medicine. We show here that female (XX) embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in mice are induced into primordial germ cell-like cells (PGCLCs), which, when aggregated with female gonadal somatic cells as reconstituted ovaries, develop pre-meiotic germ cell characteristics, including X-reactivation, imprint erasure, and cyst formation. Upon transplantation under ovarian bursa, PGCLCs in the reconstituted ovaries mature into germinal vesicle-stage oocytes, which, through in vitro maturation and fertilization, contribute to fertile offspring. Our culture system serves as a robust foundation for the investigation of key properties of female germ cells, including the acquisition of totipotency, and for the reconstitution of whole female germ-cell development in vitro.
2012-11-05 | GSE40716 | GEO
Project description:We asked whether oocyte number could be amplified through parthenogenesis of mouse oocytes, without requiring creation of a paternal genome and a genetically unique genome. Parthenotes develop to a blastocyst-like stage, and from this parthenogenetic ESCs (pESCs) can be derived with high efficiency. Like ESCs, pESCs maintain unlimited self-renewal and pluripotency, as well as germline competence. Further, we demonstrate that their expression pattern of imprinted maternal genes resembles that observed in oocytes. pESCs can be directed to differentiate into primordial germ cell-like cells (PGCLCs) and form oocytes that produce fertile pups and reconstitute ovarian endocrine functions. The transcriptome and imprinting pattern of PGCLCs differentiated from pESCs more closely approximate those of in vivo produced embryonic PGCs, than PGCLCs produced from ESCs. Parthenogenesis offers a promising route for deriving PGCLCs and amplifying oocytes by faithfully maintaining maternal genes, without fertilization.
2021-12-22 | GSE153979 | GEO
Project description:We asked whether oocyte number could be amplified through parthenogenesis of mouse oocytes, without requiring creation of a paternal genome and a genetically unique genome. Parthenotes develop to a blastocyst-like stage, and from this parthenogenetic ESCs (pESCs) can be derived with high efficiency. Like ESCs, pESCs maintain unlimited self-renewal and pluripotency, as well as germline competence. Further, we demonstrate that their expression pattern of imprinted maternal genes resembles that observed in oocytes. pESCs can be directed to differentiate into primordial germ cell-like cells (PGCLCs) and form oocytes that produce fertile pups and reconstitute ovarian endocrine functions. The transcriptome and imprinting pattern of PGCLCs differentiated from pESCs more closely approximate those of in vivo produced embryonic PGCs, than PGCLCs produced from ESCs. Parthenogenesis offers a promising route for deriving PGCLCs and amplifying oocytes by faithfully maintaining maternal genes, without fertilization.
2023-10-26 | GSE141172 | GEO
Project description:We asked whether oocyte number could be amplified through parthenogenesis of mouse oocytes, without requiring creation of a paternal genome and a genetically unique genome. Parthenotes develop to a blastocyst-like stage, and from this parthenogenetic ESCs (pESCs) can be derived with high efficiency. Like ESCs, pESCs maintain unlimited self-renewal and pluripotency, as well as germline competence. Further, we demonstrate that their expression pattern of imprinted maternal genes resembles that observed in oocytes. pESCs can be directed to differentiate into primordial germ cell-like cells (PGCLCs) and form oocytes that produce fertile pups and reconstitute ovarian endocrine functions. The transcriptome and imprinting pattern of PGCLCs differentiated from pESCs more closely approximate those of in vivo produced embryonic PGCs, than PGCLCs produced from ESCs. Parthenogenesis offers a promising route for deriving PGCLCs and amplifying oocytes by faithfully maintaining maternal genes, without fertilization.
2019-11-28 | GSE141103 | GEO
Project description:Female fertility is determined in part by the size and development of the primordial follicle pool. The current study investigates the role of glial cell-line derived neurotrophic factor (GDNF) in the regulation of primordial follicle development in the ovary. Ovaries from four-day old female rat pups were maintained in organ culture for ten days in the absence (control) or presence of GDNF or kit ligand/stem cell factor (KL). Ovaries treated with GDNF contained a significant increase in developing follicles, similar to that observed with KL treatment previously shown to promote follicle development. The actions of GDNF on the ovarian transcriptome were investigated with a microarray analysis. Immunohistochemical studies demonstrated that GDNF is localized to oocyte cytoplasm in follicles of all developmental stages, as well as to cumulus granulosa cells and theca cells in antral follicles. GDNF receptor alpha 1 (GFRalpha1) staining was localized to oocyte cytoplasm of primordial and primary follicles, and at reduced levels in oocytes of antral follicles. GFRalpha1 was present in mural granulosa cells of antral follicles, theca cells, and the ovarian surface epithelium. The localization studies were confirmed with molecular analysis. Microarray analysis was used to identify changes in the ovarian transcriptome and further elucidate the signaling network regulating early follicle development. Observations indicate that GDNF promotes primordial follicle development and mediates autocrine and paracrine cell-cell interactions required during folliculogenesis. In contrast to the testis, ovarian GDNF is predominantly produced by germ cells (oocytes) rather than somatic cells. Experiment Overall Design: RNA samples from two control groups (pooled untreated cultured ovaries) are compared to two treated groups (pooled cultured ovaries treated with GDNF)
2008-06-11 | E-GEOD-11133 | biostudies-arrayexpress
Project description:In mammalian females, quiescent primordial follicles serve as the ovarian reserve and sustain normal ovarian function and egg production via folliculogenesis. The loss of primordial follicles causes ovarian aging. Cellular senescence, characterized by cell cycle arrest and production of the senescence-associated secretory phenotype (SASP), is associated with tissue aging. In the present study, we report that some quiescent primary oocytes in primordial follicles become senescent in adult mouse ovaries. The senescent primary oocytes share senescence markers characterized in senescent somatic cells. The senescent primary oocytes were observed in young adult mouse ovaries, remained at approximately 15% of the total primary oocytes during ovarian aging from 6 months to 12 months, and accumulated in aged ovaries. Administration of a senolytic drug ABT263 to 3-month-old mice reduced the percentage of senescent primary oocytes and the transcription of the SASP cytokines in the ovary. In addition, led to increased numbers of primordial and total follicles and a higher rate of oocyte maturation and female fertility. Our study provides experimental evidence that primary oocytes, a germline cell type that is arrested in meiosis, become senescent in adult mouse ovaries and that senescent cell clearance reduced primordial follicle loss and mitigated ovarian aging phenotypes.
2024-04-30 | GSE253194 | GEO
Project description:Oocyte meiosis is an important factor affecting female reproduction. Breast cancer amplified sequence 2 (BCAS2) is a component of the spliceosome. Previous reports have shown that BCAS2 is critical in male germ cell meiosis, oocyte development, and early embryo genome integrity. However, the role of BCAS2 in oocyte meiosis has not been reported. We used Stra8-GFP-Cre mice to knock out BCAS2 during the pachytene phase of oocytes. The results of fertility tests showed that the cko mice were infertile. Morphological analysis showed that the number of primary follicles of 2M ovary was significantly reduced and follicle development was blocked. Further analysis showed that the number of primordial follicles decreased and follicle development slowed from 7dpp ovaries. Sequencing revealed that DNA damage in oocytes could not be repaired from 5dpp. There was an abnormality in meiosis, some oocytes could not reach the diplotene stage of meiosis, and more oocytes could not develop to the dictyate stage. AS analysis reveals that abnormal variable splicing of Dazl and Diaph2 Oogens-related genes in cKO mice, with involvement of the PRP19/CDC5l complex.
2024-01-01 | GSE228983 | GEO