Sexual dimorphism of the femoral neck during the adolescent growth spurt: a structural analysis

Before puberty, there are only small sex differences in body shape and composition. During adolescence, sexual dimorphism in bone, lean, and fat mass increases, giving rise to the greater size and strength of the male skeleton. The question remains as to whether there are sex differences in bone strength or simply differences in anthropometric dimensions. To test this, we applied hip structural analysis (HSA) to derive strength and geometric indices of the femoral neck using bone densitometry scans (DXA) from a 6-year longitudinal study in Canadian children. Seventy boys and sixty-eight girls were assessed annually for 6 consecutive years. At the femoral neck, cross-sectional area (CSA, an index of axial strength), subperiosteal width (SPW), and section modulus (Z, an index of bending strength) were determined, and data were analyzed using a hierarchical (random effects) modeling approach. Biological age (BA) was defined as years from age at peak height velocity (PHV). When BA, stature, and total-body lean mass (TB lean) were controlled, boys had significantly higher Z than girls at all maturity levels (P < 0.05). Controlling height and TB lean for CSA demonstrated a significant independent sex by BA interaction effect (P < 0.05). That is, CSA was greater in boys before PHV but higher in girls after PHV The coefficients contributing the greatest proportion to the prediction of CSA, SPW, and Z were height and lean mass. Because the significant sex difference in Z was relatively small and close to the error of measurement, we questioned its biological significance. The sex difference in bending strength was therefore explained by anthropometric differences. In contrast to recent hypotheses, we conclude that the CSA-lean ratio does not imply altered mechanosensitivity in girls because bending dominates loading at the neck, and the Z-lean ratio remained similar between the sexes throughout adolescence. That is, despite the greater CSA in girls, the bone is strategically placed to resist bending; hence, the bones of girls and boys adapt to mechanical challenges in a similar way. (C) 2004 Elsevier Inc. All rights reserved.

Expression profiling of purified mouse gonadal somatic cells during the critical time window of sex determination reveals novel candidate genes for human sexual dysgenesis syndromes

Despite the identification of SRY as the testis-determining gene in mammals, the genetic interactions controlling the earliest steps of male sex determination remain poorly understood. In particular, the molecular lesions underlying a high proportion of human XY gonadal dysgenesis, XX maleness and XX true hermaphroditism remain undiscovered. A number of screens have identified candidate genes whose expression is modulated during testis or ovary differentiation in mice, but these screens have used whole gonads, consisting of multiple cell types, or stages of gonadal development well beyond the time of sex determination. We describe here a novel reporter mouse line that expresses enhanced green fluorescent protein under the control of an Sf1 promoter fragment, marking Sertoli and granulosa cell precursors during the critical period of sex determination. These cells were purified from gonads of male and female transgenic embryos at 10.5 dpc (shortly after Sry transcription is activated) and 11.5 dpc (when Sox9 transcription begins), and their transcriptomes analysed using Affymetrix genome arrays. We identified 266 genes, including Dhh, Fgf9 and Ptgds, that were upregulated and 50 genes that were downregulated in 11.5 dpc male somatic gonad cells only, and 242 genes, including Fst, that were upregulated in 11.5 dpc female somatic gonad cells only. The majority of these genes are novel genes that lack identifiable homology, and several human orthologues were found to map to chromosomal loci implicated in disorders of sexual development. These genes represent an important resource with which to piece together the earliest steps of sex determination and gonad development, and provide new candidates for mutation searching in human sexual dysgenesis syndromes.

The makings of maleness: towards an integrated view of male sexual development

As the mammalian embryo develops, it must engage one of the two distinct programmes of gene activity, morphogenesis and organogenesis that characterize males and females. In males, sexual development hinges on testis determination and differentiation, but also involves many coordinated transcriptional, signalling and endocrine networks that underpin the masculinization of other organs and tissues, including the brain. Here we bring together current knowledge about these networks, identify gaps in the overall picture, and highlight the known defects that lead to disorders of male sexual development.