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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1587-1598
Number of pages12
JournalJournal of Veterinary Medical Science
Volume77
Issue number12
DOIs
Publication statusPublished - Jan 1 2016

All Science Journal Classification (ASJC) codes

  • veterinary(all)

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