Puberty marks numerous physiological processes which are initiated by central activation of the hypothalamic–pituitary–gonadal axis, followed by development of secondary sexual characteristics. To a large extent, pubertal timing is heritable, but current knowledge of genetic polymorphisms only explains few months in the large inter-individual variation in the timing of puberty. We have analysed longitudinal genome-wide changes in DNA methylation in peripheral blood samples (n = 102) obtained from 51 healthy children before and after pubertal onset. We show that changes in single methylation sites are tightly associated with physiological pubertal transition and altered reproductive hormone levels. These methylation sites cluster in and around genes enriched for biological functions related to pubertal development. Importantly, we identified that methylation of the genomic region containing the promoter of TRIP6 was co-ordinately regulated as a function of pubertal development. In accordance, immunohistochemistry identified TRIP6 in adult, but not pre-pubertal, testicular Leydig cells and circulating TRIP6 levels doubled during puberty. Using elastic net prediction models, methylation patterns predicted pubertal development more accurately than chronological age. We demonstrate for the first time that pubertal attainment of secondary sexual characteristics is mirrored by changes in DNA methylation patterns in peripheral blood. Thus, modulations of the epigenome seem involved in regulation of the individual pubertal timing.
Gonadal function in most 45,X/46,XY males, even those with genital ambiguity, seems sufficient for spontaneous puberty. Short stature and 45,X/46,XY mosaicism seem associated, but patients appear to benefit from GH treatment. Histology from two patients with biopsies from early childhood indicates that CIS originates before puberty.
Modern approaches to Ecosystem-Based Management and sustainable use of marine resources must account for the myriad of pressures (interspecies, human and environmental) affecting marine ecosystems. The network of feeding interactions between co-existing species and populations (food webs) are an important aspect of all marine ecosystems and biodiversity. Here we describe and discuss a process to evaluate the selection of operational food-web indicators for use in evaluating marine ecosystem status. This process brought together experts in food-web ecology, marine ecology, and resource management, to identify available indicators that can be used to inform marine management. Standard evaluation criteria (availability and quality of data, conceptual basis, communicability, relevancy to management) were implemented to identify practical food-web indicators ready for operational use and indicators that hold promise for future use in policy and management. The major attributes of the final suite of operational food-web indicators were structure and functioning. Indicators that represent resilience of the marine ecosystem were less developed. Over 60 potential food-web indicators were evaluated and the final selection of operational food-web indicators includes: the primary production required to sustain a fishery, the productivity of seabirds (or charismatic megafauna), zooplankton indicators, primary productivity, integrated trophic indicators, and the biomass of trophic guilds. More efforts should be made to develop thresholds-based reference points for achieving Good Environmental Status. There is also a need for international collaborations to develop indicators that will facilitate management in marine ecosystems used by multiple countries.
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