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Science (New York, N.Y.) Oct 2018Human in vitro gametogenesis may transform reproductive medicine. Human pluripotent stem cells (hPSCs) have been induced into primordial germ cell-like cells (hPGCLCs);...
Human in vitro gametogenesis may transform reproductive medicine. Human pluripotent stem cells (hPSCs) have been induced into primordial germ cell-like cells (hPGCLCs); however, further differentiation to a mature germ cell has not been achieved. Here, we show that hPGCLCs differentiate progressively into oogonia-like cells during a long-term in vitro culture (approximately 4 months) in xenogeneic reconstituted ovaries with mouse embryonic ovarian somatic cells. The hPGCLC-derived oogonia display hallmarks of epigenetic reprogramming-genome-wide DNA demethylation, imprint erasure, and extinguishment of aberrant DNA methylation in hPSCs-and acquire an immediate precursory state for meiotic recombination. Furthermore, the inactive X chromosome shows a progressive demethylation and reactivation, albeit partially. These findings establish the germline competence of hPSCs and provide a critical step toward human in vitro gametogenesis.
Topics: Cellular Reprogramming Techniques; DNA Methylation; Epigenesis, Genetic; Female; Humans; Induced Pluripotent Stem Cells; Oogenesis; Oogonia; Ovary
PubMed: 30237246
DOI: 10.1126/science.aat1674 -
Fungal Biology 2010A new fossil peronosporomycete from the upper Visean (Mississippian) of France occurs as a globose oogonium at the tip of a thin-walled hypha. The oogonium surface is...
A new fossil peronosporomycete from the upper Visean (Mississippian) of France occurs as a globose oogonium at the tip of a thin-walled hypha. The oogonium surface is prominently ornamented by densely spaced, long and subtle, straight or once to several times furcated thread-like extensions; many possess an opaque, bulb-like swelling at base. Antheridia adpressed to the oogonium are clavate and paragynous. This fossil represents only the third record of an unequivocal peronosporomycete from the Carboniferous, and thus provides important details about the evolutionary history of this group of organisms.
Topics: Fossils; France; Oogonia; Oomycetes
PubMed: 20943155
DOI: 10.1016/j.funbio.2010.03.006 -
The EMBO Journal Sep 2022In vitro oogenesis is key to elucidating the mechanism of human female germ-cell development and its anomalies. Accordingly, pluripotent stem cells have been induced...
In vitro oogenesis is key to elucidating the mechanism of human female germ-cell development and its anomalies. Accordingly, pluripotent stem cells have been induced into primordial germ cell-like cells and into oogonia with epigenetic reprogramming, yet further reconstitutions remain a challenge. Here, we demonstrate ex vivo reconstitution of fetal oocyte development in both humans and cynomolgus monkeys (Macaca fascicularis). With an optimized culture of fetal ovary reaggregates over three months, human and monkey oogonia enter and complete the first meiotic prophase to differentiate into diplotene oocytes that form primordial follicles, the source for oogenesis in adults. The cytological and transcriptomic progressions of fetal oocyte development in vitro closely recapitulate those in vivo. A comparison of single-cell transcriptomes among humans, monkeys, and mice unravels primate-specific and conserved programs driving fetal oocyte development, the former including a distinct transcriptomic transformation upon oogonia-to-oocyte transition and the latter including two active X chromosomes with little X-chromosome upregulation. Our study provides a critical step forward for realizing human in vitro oogenesis and uncovers salient characteristics of fetal oocyte development in primates.
Topics: Animals; Female; Humans; Macaca fascicularis; Meiosis; Mice; Oocytes; Oogenesis; Ovary
PubMed: 35912849
DOI: 10.15252/embj.2022110815 -
Seminars in Reproductive Medicine 2000Sexual differentiation in humans is genetically and hormonally controlled. In response to a signal from a dominant-acting gene on the Y chromosome, primordial cells in... (Review)
Review
Sexual differentiation in humans is genetically and hormonally controlled. In response to a signal from a dominant-acting gene on the Y chromosome, primordial cells in the embryonic gonad ridge differentiate into Sertoli cells and affect newly migrated germ cells to differentiate as spermatogonia, thus creating a testis. The cells of the embryonic testis secrete hormones that lead to the development of most, if not all, male secondary sexual characteristics. The Sertoli cells secrete müllerian inhibitory factor (MIF), causing regression of the müllerian ducts and of stray oogonia. The Leydig cells secrete testosterone, causing differentiation and growth of the wolffian duct structures. Dihydrotestosterone, created by metabolism of testosterone, causes growth of the prostate and phallus and fusion of the labioscrotal folds. In the absence of SRY, Sertoli cell differentiation does not occur. Rather germ cells migrating into the primordial gonad differentiate as oogonia and cause interstitial cells to differentiate as granulosa cells. In the absence of MIF and testosterone, the müllerian ducts differentiate and grow as female internal genitalia and the external genitalia are feminized. Several genes have been identified that control testis determination. These include SRY, WT1, SOX9, SF1, XH2, and DAX1. Most of these genes were discovered by analysis of rare cases of sex reversal (genetic sex of one type, gonadal sex of the other type).
Topics: Cell Differentiation; Female; Granulosa Cells; Humans; Leydig Cells; Male; Ovary; Sertoli Cells; Sex Determination Processes; Sex Differentiation; Testis; Testosterone
PubMed: 11299518
DOI: 10.1055/s-2000-13474 -
Differentiation; Research in Biological... Dec 2005A group of scientists from Harvard Medical School (Johnson et al., 2004) claims to have "established the existence of proliferative germ cells that sustain oocyte and...
A group of scientists from Harvard Medical School (Johnson et al., 2004) claims to have "established the existence of proliferative germ cells that sustain oocyte and follicle production in the postnatal mammalian ovary," expressing no doubts about their methods, results and conclusion. Johnson et al. based their conclusions of oocyte and follicular renewal from existing germline stem cells (GSC) in the postnatal mouse ovary on three types of observations: (1) A claimed discordance in follicle loss versus follicle atresia in the neonatal period and in the following pubertal and adult period; (2) immunohistochemical detection of proliferating GSC with meiotic capacity using combined markers for meiosis, germline, and mitosis; and (3) neo-folliculogenesis in ovarian chimeric grafting experiments with adult mice. Oogenesis is the process that transforms the proliferative oogonium into an oocyte through meiosis, followed by folliculogenesis and follicular and oocyte maturation. The most crucial part in producing a functional oocyte is firstly, initiation and completion of the first meiotic prophase, and secondly, enclosure of the resulting diplotene oocyte in a follicle. Neither of these two events has been shown to take place in Johnson et al.'s study of the postnatal mouse ovary. We hereby address the observations underpinning their hypothesis and conclude that it is premature to replace the paradigm that adult mammalian neo-oogenesis/folliculogenesis does not take place.
Topics: Animals; Cell Differentiation; Female; Follicular Atresia; Humans; Meiosis; Mice; Mice, Inbred C57BL; Oocytes; Ovary; Ovum
PubMed: 16351687
DOI: 10.1111/j.1432-0436.2005.00045.x -
Sexual Development : Genetics,... 2022Whether to produce sperm or eggs is the most basic and important choice from the perspective of germ cell development and differentiation. However, the induction... (Review)
Review
BACKGROUND
Whether to produce sperm or eggs is the most basic and important choice from the perspective of germ cell development and differentiation. However, the induction mechanism has not received much attention until relatively recently. This is because the issue of sexual differentiation has generally been considered a theme of somatic cells to make a testis or ovary. Basically, the sex of individual somatic cells and germ cells matches. Therefore, the sex of germ cells is thought to follow the sex of somatic cells once determined. However, researchers realized that a big, open question remained: What somatic cell signals actually induce the sexual differentiation of germ cells and what is the sex determinant in germ cells?
SUMMARY
In vitro experiments demonstrated that 2 somatic signals (BMP and RA) act directly on germ cells to induce oogonia. Therefore, these 2 signals may be referred to as oogonia inducers. From the viewpoint of germ cells, an independent experiment identified SMAD4 and STRA8, which are directly downstream of BMP and RA, respectively, acting in germ cells as female determinants. However, what about male? If these factors are female determinants, their absence may result in the induction of spermatogonia. This may be true in vivo because germ cells enter a male pathway if they do not receive these signals even in the ovary. However, this has not been confirmed in an in vitro culture system. There should be signals required for germ cells to enter a male pathway.
KEY MESSAGES
The important message is that although testis-specific factors secreted from the testis are considered to include male-inducing factors for germ cells, this may not be the case, and the male-inducing factor, if it exists, also exists in the ovary.
PubMed: 35263749
DOI: 10.1159/000520976 -
Molecular and Cellular Endocrinology Aug 2012Granulosa cells are the main ovarian source of inhibins, activins and activin-binding protein (follistatin) while germ (oogonia, oocytes) and somatic (theca, granulosa,... (Review)
Review
Granulosa cells are the main ovarian source of inhibins, activins and activin-binding protein (follistatin) while germ (oogonia, oocytes) and somatic (theca, granulosa, luteal) cells express activin receptors, signaling components and inhibin co-receptor (betaglycan). Activins are implicated in various intra-ovarian roles including germ cell survival and primordial follicle assembly; follicle growth from preantral to mid-antral stages; suppression of thecal androgen production; promotion of granulosa cell proliferation, FSHR and CYP19A1 expression; enhancement of oocyte developmental competence; retardation of follicle luteinization and/or atresia and involvement in luteolysis. Inhibins (primarily inhibin A) are produced in greatest amounts by preovulatory follicles (and corpus luteum in primates) and suppress FSH secretion through endocrine negative feedback. Together with follistatin, inhibins act locally to oppose auto-/paracrine activin (and BMP) signaling thus modulating many of the above processes. The balance between activin-inhibin shifts during follicle development with activin signalling prevailing at earlier stages but declining as inhibin and betaglycan expression rise.
Topics: Activin Receptors; Activins; Animals; Estrous Cycle; Female; Humans; Inhibins; Menstrual Cycle; Ovarian Follicle; Ovary; Signal Transduction
PubMed: 21664422
DOI: 10.1016/j.mce.2011.04.024 -
Cellular and Molecular Life Sciences :... Jul 2017In fetal females, oogonia proliferate immediately after sex determination. The progress of mitosis in oogonia proceeds so rapidly that the incompletely divided cytoplasm... (Review)
Review
In fetal females, oogonia proliferate immediately after sex determination. The progress of mitosis in oogonia proceeds so rapidly that the incompletely divided cytoplasm of the sister cells forms cysts. The oogonia will then initiate meiosis and arrest at the diplotene stage of meiosis I, becoming oocytes. Within each germline cyst, oocytes with Balbiani bodies will survive after cyst breakdown (CBD). After CBD, each oocyte is enclosed by pre-granulosa cells to form a primordial follicle (PF). Notably, the PF pool formed perinatally will be the sole lifelong oocyte source of a female. Thus, elucidating the mechanisms of CBD and PF formation is not only meaningful for solving mysteries related to ovarian development but also contributes to the preservation of reproduction. However, the mechanisms that regulate these phenomena are largely unknown. This review summarizes the progress of cellular and molecular research on these processes in mice and humans.
Topics: Animals; Cell Adhesion; Cell Differentiation; Female; Germ Cells; Humans; Meiosis; Oocytes; Ovarian Follicle
PubMed: 28197668
DOI: 10.1007/s00018-017-2480-6 -
Physiological Reviews Jan 1986Formation and differentiation of a gonad depend on finely controlled interactions between germ cells and various types of somatic cells. These interactions already begin... (Review)
Review
Formation and differentiation of a gonad depend on finely controlled interactions between germ cells and various types of somatic cells. These interactions already begin when the germ cells start migrating toward the gonadal ridge. Reaching the presumptive gonadal area on the mesonephros, the germ cells join with the mesonephric-derived cells. These mesonephric cells are probably the precursors of the steroid-producing cells. A crucial event for gonadal function is the enclosure of germ cells and somatic cells in specific germ cell compartments. Survival and differentiation of the germ cells depend on this separation. Differentiation of the steroid-producing cells depends in turn on remaining outside the cell compartments. The mechanisms directing the gonad to develop into a testis or an ovary are still obscure, but specific gene products from the sex chromosomes probably play a basic role in gonadal sex differentiation.
Topics: Animals; Cell Communication; Cell Differentiation; Cell Movement; Chimera; DNA; Disorders of Sex Development; Epithelial Cells; Epithelium; Female; Germ Cells; Gonadal Steroid Hormones; H-Y Antigen; Leydig Cells; Male; Meiosis; Mesoderm; Mesonephros; Oocytes; Oogonia; Ovarian Follicle; Ovary; Phenotype; Sertoli Cells; Sex Differentiation; Spermatogonia; Stem Cells; Testis; Testosterone; X Chromosome; Y Chromosome
PubMed: 3511481
DOI: 10.1152/physrev.1986.66.1.71 -
Microbios 2001The effect of mercuric chloride on the germination and growth of swarmers and subsequent induction of oogonia was studied in Oedogonium hatei Kam. (Oedogoniales,...
The effect of mercuric chloride on the germination and growth of swarmers and subsequent induction of oogonia was studied in Oedogonium hatei Kam. (Oedogoniales, Chorophyceae). HgCl2 within the concentration range of 0.01 to 1.0 mg/l produced a progressive increase in the initiation of germination and reduction in the growth of the alga. The percentage of oogonia formed, and mature oogonia developed, decreased linearly with a rise in the concentrations of HgCl2 employed. The results showed that 1 mg/l HgCl2 was highly toxic to the growth and/or multiplication of zoospores and further development of sexual structures in O. hatei. The germination of zoospores and growth of germlings were so severely affected that induction of oogonia remained completely inhibited at 1 mg/l HgCl2. Moreover, 2 mg/l of HgCl2 was lethal to the asexual zoospores.
Topics: Chlorophyta; Culture Media; Disinfectants; Dose-Response Relationship, Drug; Mercuric Chloride
PubMed: 11549240
DOI: No ID Found