Transcriptional progression during meiotic prophase I reveals sex-specific features and X chromosome dynamics in human fetal female germline

During gametogenesis in mammals, meiosis ensures the production of haploid gametes. The timing and length of meiosis to produce female and male gametes differ considerably. In contrast to males, meiotic prophase I in females initiates during development. Hence, the knowledge regarding progression through meiotic prophase I is mainly focused on human male spermatogenesis and female oocyte maturation during adulthood. Therefore, it remains unclear how the different stages of meiotic prophase I between human oogenesis and spermatogenesis compare. Analysis of single-cell transcriptomics data from human fetal germ cells (FGC) allowed us to identify the molecular signatures of female meiotic prophase I stages leptotene, zygotene, pachytene and diplotene. We have compared those between male and female germ cells in similar stages of meiotic prophase I and revealed conserved and specific features between sexes. We identified not only key players involved in the process of meiosis, but also highlighted the molecular components that could be responsible for changes in cellular morphology that occur during this developmental period, when the female FGC acquire their typical (sex-specific) oocyte shape as well as sex-differences in the regulation of DNA methylation. Analysis of X-linked expression between sexes during meiotic prophase I suggested a transient X-linked enrichment during female pachytene, that contrasts with the meiotic sex chromosome inactivation in males. Our study of the events that take place during meiotic prophase I provide a better understanding not only of female meiosis during development, but also highlights biomarkers that can be used to study infertility and offers insights in germline sex dimorphism in humans.

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Dynamics of Meiotic Sex Chromosome Inactivation and Pachytene Activation in Mice Spermatogenesis

10.1101/665372 ◽

2019 ◽

Author(s):

Ábel Vértesy ◽

Javier Frias-Aldeguer ◽

Zeliha Sahin ◽

Nicolas Rivron ◽

Alexander van Oudenaarden ◽

...

Keyword(s):

Single Molecule ◽

Meiotic Prophase ◽

Sex Chromosome ◽

Chromosome Inactivation ◽

Specific Gene ◽

Prophase I ◽

Meiotic Prophase I ◽

Meiotic Sex Chromosome Inactivation ◽

Sex Chromosome Inactivation

AbstractDuring germ cell development, cells undergo a drastic switch from mitosis to meiosis to form haploid germ cells. Sequencing and computational technologies now allow studying development at the single-cell level. Here we developed a multiplexed trajectory reconstruction to create a high-resolution developmental map of spermatogonia and prophase-I spermatocytes from testes of a Dazl-GFP reporter mouse. We identified three main transitions in the meiotic prophase-I: meiotic entry, the meiotic sex chromosome inactivation (MSCI), and concomitant pachytene activation. We validated the key features of these transitions in vivo using single molecule FISH. Focusing on MSCI, we found that 34% of sex chromosomal genes are induced shortly before MSCI, that silencing time is diverse and correlates with specific gene functions. These highlight a previously underappreciated level of regulation of MSCI. Finally, we found that spermatozoal genes in pachytene are activated in a temporal pattern reflecting the future anatomic and functional order of the sperm cell. Altogether we highlighted how precise and sequential changes in gene expression regulate cellular states in meiotic prophase-I.

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105. MEIOTIC ACROBATS: MONOTREME SEX CHROMOSOME ORGANISATION DURING SPERMATOGENESIS

Reproduction Fertility and Development ◽

10.1071/srb10abs105 ◽

2010 ◽

Vol 22 (9) ◽

pp. 23

Author(s):

F. Grutzner ◽

A. Casey ◽

T. Daish

Keyword(s):

Sex Chromosomes ◽

Meiotic Prophase ◽

Sex Chromosome ◽

National Academy Of Sciences ◽

Prophase I ◽

Meiotic Prophase I ◽

Meiotic Sex Chromosome Inactivation ◽

Y Chromosomes ◽

Specific Order ◽

Active Transcription

Monotremes feature an extraordinarily complex sex chromosome system which shares extensive homology with bird sex chromosomes but no homology to sex chromosomes of other mammals (1,2,3). At meiotic prophase I the ten sex chromosomes in platypus (nine in echidna) assemble in a sex chromosome chain. We previously identified the multiple sex chromosomes in platypus and echidna that form the meiotic chain in males (1,2,4). We showed that sex chromosomes assembly in the chain in a specific order (5) and that they segregate alternately (1). In secondary spermatocytes we observed clustering of X and Y chromosomes in sperm (6). Our current research investigates the formation of the synaptonemal complex, recombination and meiotic silencing of monotreme sex chromosomes. Meiotic sex chromosome inactivation (MSCI) has been observed in eutherian mammals, marsupials and birds but has so far not been investigated experimentally in monotremes. We found that during pachytene the X5Y5 end of the chain closely associates with the nucleolus and accumulates repressive chromatin marks (e.g. histone variant mH2A). In contrast to the differential accumulation of mH2A we observe extensive loading of the cohesin SMC3 on sex chromosomes in particular during the pachytene stage of meiotic prophase I. We have also used markers of active transcription and gene expression analysis to investigate gene activity in platypus meiotic cells. I will discuss how these findings contribute to our current understanding of the meiotic organisation of monotreme sex chromosomes and the evolution of MSCI in birds and mammals. (1) Grützner et al. (2004), Nature 432: 913–917.(2) Rens et al. (2007), Genome Biology 16;8(11): R243.(3) Veyrunes et al. (2008), Genome Research, 18(6): 995–1004.(4) Rens et al. (2004), Proceedings of the National Academy of Sciences USA. 101 (46): 16 257–16 261.(5) Daish et al. (2009), Reprod Fertil Dev. 21(8): 976–84.(6) Tsend-Ayush et al. (2009), Chromosoma 118(1): 53–69.

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Speedy A–Cdk2 binding mediates initial telomere–nuclear envelope attachment during meiotic prophase I independent of Cdk2 activation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1618465114 ◽

2016 ◽

Vol 114 (3) ◽

pp. 592-597 ◽

Cited By ~ 25

Author(s):

Zhaowei Tu ◽

Mustafa Bilal Bayazit ◽

Hongbin Liu ◽

Jingjing Zhang ◽

Kiran Busayavalasa ◽

...

Keyword(s):

Nuclear Envelope ◽

Germ Cells ◽

Meiotic Prophase ◽

Homologous Pairing ◽

Male And Female ◽

Homologous Chromosomes ◽

Cyclin Dependent Kinases ◽

Prophase I ◽

Meiotic Prophase I ◽

Localization Domain

Telomere attachment to the nuclear envelope (NE) is a prerequisite for chromosome movement during meiotic prophase I that is required for pairing of homologous chromosomes, synapsis, and homologous recombination. Here we show that Speedy A, a noncanonical activator of cyclin-dependent kinases (Cdks), is specifically localized to telomeres in prophase I male and female germ cells in mice, and plays an essential role in the telomere–NE attachment. Deletion of Spdya in mice disrupts telomere–NE attachment, and this impairs homologous pairing and synapsis and leads to zygotene arrest in male and female germ cells. In addition, we have identified a telomere localization domain on Speedy A covering the distal N terminus and the Cdk2-binding Ringo domain, and this domain is essential for the localization of Speedy A to telomeres. Furthermore, we found that the binding of Cdk2 to Speedy A is indispensable for Cdk2’s localization on telomeres, suggesting that Speedy A and Cdk2 might be the initial components that are recruited to the NE for forming the meiotic telomere complex. However, Speedy A-Cdk2–mediated telomere–NE attachment is independent of Cdk2 activation. Our results thus indicate that Speedy A and Cdk2 might mediate the initial telomere–NE attachment for the efficient assembly of the telomere complex that is essential for meiotic prophase I progression.

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