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

Autor: Nobuhiko Hamazaki, Go Nagamatsu, Orie Hikabe, Yuki Takada, Norio Hamada, Kiyoko Kato, Katsuhiko Hayashi, So Shimamoto
Rok vydání: 2020
Předmět:
Male
Cancer Research
Physiology
Cellular differentiation
Gene Expression
QH426-470
Oogenesis
Mice
Homologous Chromosomes
0302 clinical medicine
Animal Cells
Reproductive Physiology
Y Chromosome
Medicine and Health Sciences
Genetics (clinical)
X chromosome
Mice
Inbred ICR
0303 health sciences
Sex Chromosomes
Chromosome Biology
Cell Differentiation
X Chromosomes
Cell biology
medicine.anatomical_structure
OVA
Female
Cellular Types
Germ cell
Research Article
X Chromosome
Mice
Inbred Strains
Biology
Chromosomes
03 medical and health sciences
Genetics
Homologous chromosome
medicine
Animals
Molecular Biology
Embryonic Stem Cells
Ecology
Evolution
Behavior and Systematics
Gametogenesis
030304 developmental biology
Biology and Life Sciences
Cell Biology
Embryonic stem cell
Mice
Inbred C57BL
Germ Cells
Oocytes
Oocyte differentiation
030217 neurology & neurosurgery
Developmental Biology
Zdroj: PLoS Genetics, Vol 16, Iss 3, p e1008676 (2020)
PLoS Genetics
ISSN: 1553-7404
DOI: 10.1371/journal.pgen.1008676
Popis: A set of sex chromosomes is required for gametogenesis in both males and females, as represented by sex chromosome disorders causing agametic phenotypes. Although studies using model animals have investigated the functional requirement of sex chromosomes, involvement of these chromosomes in gametogenesis remains elusive. Here, we elicit a germ cell-intrinsic effect of sex chromosomes on oogenesis, using a novel culture system in which oocytes were induced from embryonic stem cells (ESCs) harboring XX, XO or XY. In the culture system, oogenesis using XO and XY ESCs was severely disturbed, with XY ESCs being more strongly affected. The culture system revealed multiple defects in the oogenesis of XO and XY ESCs, such as delayed meiotic entry and progression, and mispairing of the homologous chromosomes. Interestingly, Eif2s3y, a Y-linked gene that promotes proliferation of spermatogonia, had an inhibitory effect on oogenesis. This led us to the concept that male and female gametogenesis appear to be in mutual conflict at an early stage. This study provides a deeper understanding of oogenesis under a sex-reversal condition.
Author summary Oogenesis is a highly sex-dependent differentiation process that commences at the mid-gestation stage. Oogenesis is severely disturbed in XO and XY females, although the mechanisms underlying the disturbance are still elusive. In this study, we subjected XO and XY ES cells to an in vitro culture system, in which female (XX) ES cells differentiate into functional oocytes. Our results showed that oogenesis from XO and XY ES cells was severely disturbed due to defective processes such as delayed meiotic initiation/progression, aberrant gene expression and mispairing of homologous chromosomes. In addition, our results demonstrate that a Y-linked gene, Eif2s3y that promotes spermatogenesis, has conversely a negative impact on oogenesis. This study provides a culture system that serves as a useful model of sex reversal and contributes the concept of a substantial germ cell-intrinsic conflict between male and female gametogenesis. Further study using the culture system will reveal molecular insights into infertility with sex chromosome disorder(s).
Databáze: OpenAIRE
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