Document Detail

Masculine epigenetic sex marks of the CYP19A1/aromatase promoter in genetically male chicken embryonic gonads are resistant to estrogen-induced phenotypic sex conversion.
MedLine Citation:
PMID:  22539680     Owner:  NLM     Status:  MEDLINE    
Sex of birds is genetically determined through inheritance of the ZW sex chromosomes (ZZ males and ZW females). Although the mechanisms of avian sex determination remains unknown, the genetic sex is experimentally reversible by in ovo exposure to exogenous estrogens (ZZ-male feminization) or aromatase inhibitors (ZW-female masculinization). Expression of various testis- and ovary-specific marker genes during the normal and reversed gonadal sex differentiation in chicken embryos has been extensively studied, but the roles of sex-specific epigenetic marks in sex differentiation are unknown. In this study, we show that a 170-nt region in the promoter of CYP19A1/aromatase, a key gene required for ovarian estrogen biosynthesis and feminization of chicken embryonic gonads, contains highly quantitative, nucleotide base-level epigenetic marks that reflect phenotypic gonadal sex differentiation. We developed a protocol to feminize ZZ-male chicken embryonic gonads in a highly quantitative manner by direct injection of emulsified ethynylestradiol into yolk at various developmental stages. Taking advantage of this experimental sex reversal model, we show that the epigenetic sex marks in the CYP19A1/aromatase promoter involving DNA methylation and histone lysine methylation are feminized significantly but only partially in sex-converted gonads even when morphological and transcriptional marks of sex differentiation show complete feminization, being indistinguishable from gonads of normal ZW females. Our study suggests that the epigenetic sex of chicken embryonic gonads is more stable than the morphologically or transcriptionally characterized sex differentiation, suggesting the importance of the nucleotide base-level epigenetic sex in gonadal sex differentiation.
Haley L Ellis; Keiko Shioda; Noël F Rosenthal; Kathryn R Coser; Toshi Shioda
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-07-26
Journal Detail:
Title:  Biology of reproduction     Volume:  87     ISSN:  1529-7268     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-27     Completed Date:  2012-11-30     Revised Date:  2013-07-02    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  23, 1-12     Citation Subset:  IM    
Molecular Profiling Laboratory, Massachusetts General Hospital Center for Cancer Research and Harvard Medical School, Charlestown, Massachusetts, USA.
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MeSH Terms
Aromatase / genetics*
Avian Proteins / genetics*
Chick Embryo
Chickens / genetics*
CpG Islands
DNA Methylation / drug effects
Disorders of Sex Development / chemically induced,  embryology
Epigenesis, Genetic / drug effects
Ethinyl Estradiol / administration & dosage
Feminization / chemically induced,  embryology
Genetic Markers
Ovary / drug effects,  embryology
Promoter Regions, Genetic
RNA, Messenger / genetics,  metabolism
Sex Determination Processes
Sex Differentiation / drug effects,  genetics
Testis / drug effects,  embryology
Grant Support
R7963//PHS HHS
Reg. No./Substance:
0/Avian Proteins; 0/Genetic Markers; 0/RNA, Messenger; 57-63-6/Ethinyl Estradiol; EC

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