Ontogenic and morphological study of gonadal formation in genetically-modified sex reversal XYPOS mice

Yuria UMEMURA; Ryosuke MIYAMOTO; Rie HASHIMOTO; Kyoko KINOSHITA; Takuya OMOTEHARA; Daichi NAGAHARA; Tetsushi HIRANO; Naoto KUBOTA; Kiichi MINAMI; Shogo YANAI; Natsumi MASUDA; Hideto YUASA; Youhei MANTANI; Eiko MATSUO; Toshifumi YOKOYAMA; Hiroshi KITAGAWA; Nobuhiko HOSHI

doi:10.1292/jvms.15-0292

Laboratory Animal Science

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

Yuria UMEMURA, Ryosuke MIYAMOTO, Rie HASHIMOTO, Kyoko KINOSHITA, Takuya OMOTEHARA, Daichi NAGAHARA, Tetsushi HIRANO, Naoto KUBOTA, Kiichi MINAMI, Shogo YANAI, Natsumi MASUDA, Hideto YUASA, Youhei MANTANI, Eiko MATSUO, Toshifumi YOKOYAMA, Hiroshi KITAGAWA, Nobuhiko HOSHI

Author information

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

Keywords: C57BL/6, Musm. musculus poschiavinus, sex reversal, Sox9, Sry

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2015 Volume 77 Issue 12 Pages 1587-1598

DOI https://doi.org/10.1292/jvms.15-0292

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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-XY^POS) has been shown to induce sex reversal (75%: bilateral ovary, 25%: true hermaphrodites). However, our B6N-XY^POS mice, which were generated by backcrossing of B6J-XY^POS 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-XY^POS 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-XY^POS gonads occurred 2–3 tail somites later than those in B6N-XY^B6 gonads, but earlier than those in B6J-XY^POS, respectively. It is possible that such a small difference in timing of the Sry expression underlies testicular development in our B6N-XY^POS. Our study is the first to histologically show the expression and ectopic localization of a female-related gene in the XY^POS testes and a male-related gene in the XY^POS 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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