Disorders of Sex Development Expose Transcriptional Autonomy of Genetic Sex and Androgen-programmed Hormonal Sex in Human Blood Leukocytes

Overview

Journal BMC Genomics

Publisher Biomed Central

Specialty Genetics

Date 2009 Jul 3

PMID 19570224

Citations 5

Authors

Paul-Martin Holterhus

Jan-Hendrik Bebermeier

Ralf Werner

Janos Demeter

Annette Richter-Unruh

Gunnar Cario

Mahesh Appari

Reiner Siebert

Felix Riepe

James D Brooks

Olaf Hiort

Affiliations

Soon will be listed here.

Abstract

Background: Gender appears to be determined by independent programs controlled by the sex-chromosomes and by androgen-dependent programming during embryonic development. To enable experimental dissection of these components in the human, we performed genome-wide profiling of the transcriptomes of peripheral blood mononuclear cells (PBMC) in patients with rare defined "disorders of sex development" (DSD, e.g., 46, XY-females due to defective androgen biosynthesis) compared to normal 46, XY-males and 46, XX-females.

Results: A discrete set of transcripts was directly correlated with XY or XX genotypes in all individuals independent of male or female phenotype of the external genitalia. However, a significantly larger gene set in the PBMC only reflected the degree of external genital masculinization independent of the sex chromosomes and independent of concurrent post-natal sex steroid hormone levels. Consequently, the architecture of the transcriptional PBMC-"sexes" was either male, female or even "intersex" with a discordant alignment of the DSD individuals' genetic and hormonal sex signatures.

Conclusion: A significant fraction of gene expression differences between males and females in the human appears to have its roots in early embryogenesis and is not only caused by sex chromosomes but also by long-term sex-specific hormonal programming due to presence or absence of androgen during the time of external genital masculinization. Genetic sex and the androgen milieu during embryonic development might therefore independently modulate functional traits, phenotype and diseases associated with male or female gender as well as with DSD conditions.

Citing Articles

Sex Differences in HIV Infection.

Scully E Curr HIV/AIDS Rep. 2018; 15(2):136-146.

PMID: 29504062 PMC: 5882769. DOI: 10.1007/s11904-018-0383-2.

Management of disorders of sex development.

Hiort O, Birnbaum W, Marshall L, Wunsch L, Werner R, Schroder T Nat Rev Endocrinol. 2014; 10(9):520-9.

PMID: 25022812 DOI: 10.1038/nrendo.2014.108.

Androgen receptor function links human sexual dimorphism to DNA methylation.

Ammerpohl O, Bens S, Appari M, Werner R, Korn B, Drop S PLoS One. 2013; 8(9):e73288.

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The differential role of androgens in early human sex development.

Hiort O BMC Med. 2013; 11:152.

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From mental disorder to iatrogenic hypogonadism: dilemmas in conceptualizing gender identity variants as psychiatric conditions.

Meyer-Bahlburg H Arch Sex Behav. 2009; 39(2):461-76.

PMID: 19851856 PMC: 2844928. DOI: 10.1007/s10508-009-9532-4.

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