Germ cell-intrinsic effects of sex chromosomes on early oocyte differentiation in mice

Hamada, Norio; Hamazaki, Nobuhiko; Shimamoto, So; Hikabe, Orie; Nagamatsu, Go; Takada, Yuki; Kato, Kiyoko; Hayashi, Kozaburo

doi:10.1371/journal.pgen.1008676

Cited by 22 publications

(27 citation statements)

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“…However, to perform the experiment in a more physiological niche, without external cues, no retinoic acid was added to the IVDi culture and the IVDi tissue was cultured for 11 days until primary follicles had formed. We then stained the entire whole‐mount tissue for DAZL and SYCP3 to identify mature (DAZL+) and meiotic (SYCP3+) germ cells and could observe on average 200 oocytes in cysts per aggregate and moreover, around 50 primary follicles (Fig 4H and I ), similar to what has been observed previously (Hamada et al , 2020 ), showing that our XGFP− PGCLCs could indeed mature further.…”

Section: Resultssupporting

confidence: 82%

Controlled X‐chromosome dynamics defines meiotic potential of female mouse in vitro germ cells

et al. 2022

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The mammalian germline is characterized by extensive epigenetic reprogramming during its development into functional eggs and sperm. Specifically, the epigenome requires resetting before parental marks can be established and transmitted to the next generation. In the female germline, X-chromosome inactivation and reactivation are among the most prominent epigenetic reprogramming events, yet very little is known about their kinetics and biological function. Here, we investigate X-inactivation and reactivation dynamics using a tailor-made in vitro system of primordial germ cell-like cell (PGCLC) differentiation from mouse embryonic stem cells. We find that X-inactivation in PGCLCs in vitro and in germ cell-competent epiblast cells in vivo is moderate compared to somatic cells, and frequently characterized by escaping genes. X-inactivation is followed by step-wise X-reactivation, which is mostly completed during meiotic prophase I. Furthermore, we find that PGCLCs which fail to undergo X-inactivation or reactivate too rapidly display impaired meiotic potential. Thus, our data reveal fine-tuned X-chromosome remodelling as a critical feature of female germ cell development towards meiosis and oogenesis.

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Section: Resultssupporting

confidence: 82%

Controlled X‐chromosome dynamics defines meiotic potential of female mouse in vitro germ cells

et al. 2022

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“…We then stained the entire whole-mount tissue for DAZL and SYCP3 to identify mature (DAZL+) and meiotic (SYCP3+) germ cells and could observe on average 200 oocytes in cysts per aggregate and moreover around 50 primary follicles (Fig. 5H and I), similar to what has been observed previously (Hamada et al, 2020). Taken together, our XGFP-PGCLCs are able to enter prophase I and to mature into primary…”

Section: Xgfp-pgclcs Can Enter Meiotic Prophase and Undergo Oocyte Maturationsupporting

confidence: 83%

“…As in the case of pluripotency, reactivation of dosagesensitive X-linked genes could enable the initiation of the meiotic gene expression program by promoting the derepression and upregulation of meiotic genes (Hill et al, 2018;Yamaguchi et al, 2012). The absence of double X dosage and/or abnormalities in meiotic pairing ability greatly diminishes the success rate of XO and XY germ cells to pass through meiotic prophase due to delay of meiotic initiation and meiotic arrest when compared to XX germ cells (Hamada et al, 2020). Therefore, equalizing the chromatin state between the heterochromatic inactive X and euchromatic active X by X-reactivation could be a necessary step in order to allow X-X chromosome pairing during meiotic prophase.…”

Section: Discussionmentioning

confidence: 99%

A temporally controlled sequence of X-chromosome inactivation and reactivation defines female mouse in vitro germ cells with meiotic potential

Severino

Bauer

Mattimoe

et al. 2021

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The early mammalian germ cell lineage is characterized by extensive epigenetic reprogramming, which is required for the maturation into functional eggs and sperm. In particular, the epigenome needs to be reset before parental marks can be established and then transmitted to the next generation. In the female germ line, reactivation of the inactive X chromosome is one of the most prominent epigenetic reprogramming events, and despite its scale involving an entire chromosome affecting hundreds of genes, very little is known about its kinetics and biological function. Here we investigate X-chromosome inactivation and reactivation dynamics by employing a tailor-made in vitro system to visualize the X-status during differentiation of primordial germ cell-like cells (PGCLCs) from female mouse embryonic stem cells (ESCs). We find that the degree of X-inactivation in PGCLCs is moderate when compared to somatic cells and characterized by a large number of genes escaping full inactivation. Nevertheless, PGCLCs that fail to undergo X-inactivation show an abnormal gene expression signature and deficiencies in meiotic entry. Subsequent to X-inactivation we observe gradual step-wise X-reactivation, which is mostly completed by the end of meiotic prophase I. Cells deviating from these progressive kinetics and undergoing X-reactivation too rapidly fail to enter a meiotic trajectory. Our data reveals that a fine-tuned X-inactivation and -reactivation cycle is a critical feature of female germ cell developmental competence towards meiosis and oogenesis

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“…However, Ddx3y shares RNA helicase activity and may be exchangeable with its X homolog Ddx3x (Sekiguchi et al, 2004;Matsumura et al, 2019). Eif2s3y and Eif2s3x also share redundant functions in the proliferation of spermatogonia although they exhibit distinct activities when overexpressed in the ES-derived female germline (Yamauchi et al, 2016;Hamada et al, 2020). Uty encodes a protein, which can partially compensate for the embryonic lethality by null mutation of its X-homolog Utx (Kdm6a) although UTY has a lower histone demethylase activity than UTX (Shpargel et al, 2012;Welstead et al, 2012).…”

Section: Sex Chromosome Dosage Dependent Differentially Expressed Genesmentioning

confidence: 99%

“…Moreover, XO female mice are fertile, suggesting that one X chromosome is sufficient for rendering the oocyte to become competent for embryonic development in the mouse. Nonetheless, XX and XO oocytes are not equal when exogenous genes are expressed (Vernet et al, 2014b;Hamada et al, 2020). In the current study, we produced XO females by using the male mouse carrying Patchy Fur (Paf) mutation on the X chromosome, which was provided on the C3H/HeSnJ background from the Jackson Laboratory.…”

Section: Introductionmentioning

confidence: 99%

Effects of the Sex Chromosome Complement, XX, XO, or XY, on the Transcriptome and Development of Mouse Oocytes During Follicular Growth

et al. 2021

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The sex chromosome complement, XX or XY, determines sexual differentiation of the gonadal primordium into a testis or an ovary, which in turn directs differentiation of the germ cells into sperm and oocytes, respectively, in eutherian mammals. When the X monosomy or XY sex reversal occurs, XO and XY females exhibit subfertility and infertility in the mouse on the C57BL/6J genetic background, suggesting that functional germ cell differentiation requires the proper sex chromosome complement. Using these mouse models, we asked how the sex chromosome complement affects gene transcription in the oocytes during follicular growth. An oocyte accumulates cytoplasmic components such as mRNAs and proteins during follicular growth to support subsequent meiotic progression, fertilization, and early embryonic development without de novo transcription. However, how gene transcription is regulated during oocyte growth is not well understood. Our results revealed that XY oocytes became abnormal in chromatin configuration, mitochondria distribution, and de novo transcription compared to XX or XO oocytes near the end of growth phase. Therefore, we compared transcriptomes by RNA-sequencing among the XX, XO, and XY oocytes of 50–60 µm in diameter, which were still morphologically comparable. The results showed that the X chromosome dosage limited the X-linked and autosomal gene transcript levels in XO oocytes whereas many genes were transcribed from the Y chromosome and made the transcriptome in XY oocytes closer to that in XX oocytes. We then compared the transcript levels of 3 X-linked, 3 Y-linked and 2 autosomal genes in the XX, XO, and XY oocytes during the entire growth phase as well as at the end of growth phase using quantitative RT-PCR. The results indicated that the transcript levels of most genes increased with oocyte growth while largely maintaining the X chromosome dosage dependence. Near the end of growth phase, however, transcript levels of some X-linked genes did not increase in XY oocytes as much as XX or XO oocytes, rendering their levels much lower than those in XX oocytes. Thus, XY oocytes established a distinct transcriptome at the end of growth phase, which may be associated with abnormal chromatin configuration and mitochondria distribution.

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Germ cell-intrinsic effects of sex chromosomes on early oocyte differentiation in mice

Cited by 22 publications

References 50 publications

Controlled X‐chromosome dynamics defines meiotic potential of female mouse in vitro germ cells

Controlled X‐chromosome dynamics defines meiotic potential of female mouse in vitro germ cells

A temporally controlled sequence of X-chromosome inactivation and reactivation defines female mouse in vitro germ cells with meiotic potential

Effects of the Sex Chromosome Complement, XX, XO, or XY, on the Transcriptome and Development of Mouse Oocytes During Follicular Growth

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