Tuesday, July 7, 2009

Sexual Development Determined “In Utero” By Two Independent Programs of Sex-Chromosomes and Androgen Influence

Below is the abstract of a hot new paper that elaborates on the "two layers" of sexual/gender programming that make you the "sexual somebody" you are at the time of birth. I will post more on this paper soon.

Disorders of sex development expose transcriptional autonomy of genetic sex and androgen-programmed hormonal sex in human blood leukocytes
Paul-Martin Holterhus , Jan-Hendrik Bebermeier , Ralf Werner , Janos Demeter , Annette Richter-Unruh , Gunnar Cario , Mahesh Appari , Reiner Siebert , Felix Riepe , James D Brooks and Olaf Hiort
BMC Genomics 2009, 10:292doi:10.1186/1471-2164-10-292
Published: 1 July 2009

Abstract (provisional)

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.

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.

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.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.