Stepwise approach to oocyte depletion in Sry mutated XY female mice

Akihiko Sakashita, Takuya Wakai, Yukiko Kawabata, Chiaki Nishimura, Yusuke Sotomaru, Tomohiro Kono

Research output: Contribution to journalArticlepeer-review

Abstract

Little is known regarding the mechanisms underlying infertility in male-to-female sex-reversed females. To gain a better understanding of germ cell dysfunction in this condition, we produced XYsry−-females via the CRISPR/Cas9 system in C57BL/6 inbred strain mice. Mutant mice showed severe attrition of germ cells during foetal development, resulting in depletion of ovarian germ cells before sexual maturation. Comprehensive transcriptome analysis of embryonic day 13.5 primordial germ cells (PGCs) and postnatal day 1 oocytes demonstrated that XYsry−-PGCs had already deviated from the developmental process at the mitotic stage. In addition, XYsry−-oocytes resulted in meiotic disruption and developmental failure, and the genes related to these processes were significantly changed. This grievous disruption, which caused germ cell deterioration in XYsry−-females, was shown to proceed from the germ cells themselves. These results provide novel insight into the germ cell depletion of sex-reversed mice as well as into disorders of sex differentiation in human, such as ‘Swyer syndrome’, wherein patients present as typical females albeit with an XY karyotype and infertile.

Original languageEnglish
JournalUnknown Journal
DOIs
Publication statusPublished - Jun 6 2017
Externally publishedYes

Keywords

  • Cell death program.
  • Germ cell depletion
  • Infertility of XY female
  • Sex-reversed mice
  • Transcriptome analysis
  • Wnt signaling
  • XY PGCs/oocytes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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