title: Ontogenic and morphological study of gonadal formation in genetically-modified sex reversal XY(POS) mice.
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.
authors.affiliation: Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657-8501, Japan.
authors.forename: Yuria
authors.initials: Y
authors.lastname: Umemura
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Miyamoto
authors.forename: Rie
authors.initials: R
authors.lastname: Hashimoto
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kinoshita
authors.forename: Takuya
authors.initials: T
authors.lastname: Omotehara
authors.forename: Daichi
authors.initials: D
authors.lastname: Nagahara
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Hirano
authors.forename: Naoto
authors.initials: N
authors.lastname: Kubota
authors.forename: Kiichi
authors.initials: K
authors.lastname: Minami
authors.forename: Shogo
authors.initials: S
authors.lastname: Yanai
authors.forename: Natsumi
authors.initials: N
authors.lastname: Masuda
authors.forename: Hideto
authors.initials: H
authors.lastname: Yuasa
authors.forename: Youhei
authors.initials: Y
authors.lastname: Mantani
authors.forename: Eiko
authors.initials: E
authors.lastname: Matsuo
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hoshi
mesh_terms: D000483:Alleles; D000818:Animals; D033481:Chromosomes, Mammalian / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010053:Ovary / Q000254:growth & development*; D050090:Ovotesticular Disorders of Sex Development / Q000235:genetics*; D019849:Sex Determination Processes / Q000235:genetics / Q000502:physiology*; D051876:Sex-Determining Region Y Protein / Q000235:genetics / Q000378:metabolism; D013737:Testis / Q000254:growth & development*; D014960:X Chromosome / Q000235:genetics*; D014998:Y Chromosome / Q000235:genetics*
chemical_list: D051876:Sex-Determining Region Y Protein; C497746:Sry protein, mouse