Ontogenic and morphological study of gonadal formation in genetically-modified sex reversal XY<sup>POS</sup> mice

  • UMEMURA Yuria
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • MIYAMOTO Ryosuke
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • HASHIMOTO Rie
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • KINOSHITA Kyoko
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • OMOTEHARA Takuya
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • NAGAHARA Daichi
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • HIRANO Tetsushi
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • KUBOTA Naoto
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • MINAMI Kiichi
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • YANAI Shogo
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • MASUDA Natsumi
    Laboratory of Histophysiology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • YUASA Hideto
    Laboratory of Histophysiology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • MANTANI Youhei
    Laboratory of Histophysiology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • MATSUO Eiko
    Laboratory of Microbiology and Immunology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • YOKOYAMA Toshifumi
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • KITAGAWA Hiroshi
    Laboratory of Histophysiology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • HOSHI Nobuhiko
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan

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  • Ontogenic and morphological study of gonadal formation in genetically-modified sex reversal XY[POS] mice

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Abstract

Mammalian sexual fate is determined by the presence or absence of sex determining region of the Y chromosome (Sry) in the “bipotential” gonads. Recent studies have demonstrated that both male and female sexual development are induced by distinct and active genetic pathways. Breeding the Y chromosome from Mus m. domesticus poschiavinus (POS) strains into C57BL/6J (B6J) mice (B6J-XYPOS) has been shown to induce sex reversal (75%: bilateral ovary, 25%: true hermaphrodites). However, our B6N-XYPOS mice, which were generated by backcrossing of B6J-XYPOS on an inbred B6N-XX, develop as males (36%: bilateral testis with fertility as well as bilateral ovary (34%), and the remainder develop as true hermaphrodites. Here, we investigated in detail the expressions of essential sex-related genes and histological features in B6N-XYPOS mice from the fetal period to adulthood. The onsets of both Sry and SRY-box 9 (Sox9) expressions as determined spatiotemporally by whole-mount immunohistochemistry in the B6N-XYPOS gonads occurred 2–3 tail somites later than those in B6N-XYB6 gonads, but earlier than those in B6J-XYPOS, respectively. It is possible that such a small difference in timing of the Sry expression underlies testicular development in our B6N-XYPOS. Our study is the first to histologically show the expression and ectopic localization of a female-related gene in the XYPOS testes and a male-related gene in the XYPOS ovaries. The results from these and previous experiments indicate that the interplay between genome variants, epigenetics and developmental gene regulation is crucial for testis development.

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