Endocrine Abstracts

Reproductive disorders in males that manifest at birth (cryptorchidism, hypospadias), or young adulthood (low sperm count, lower testosterone levels, testicular cancer) may share a common origin and constitute a ‘testicular dysgenesis syndrome’ (TDS). Normal reproductive tract development is programmed by androgens within the ‘masculinisation programming window’ (MPW, e15.5–e18.5-rats; ~8–14 weeks’ gestation-humans). In rats, TDS disorders ca...

Fetal Leydig cell (LC) dysfunction leads to human male reproductive disorders (‘testicular dysgenesis syndrome’; TDS) that manifest at birth (cryptorchidism, hypospadias) or in young adulthood (low sperm count, testicular germ cell cancer). The factors regulating fetal LC function in early gestation are unknown, but can be disrupted in rats by environmental chemicals (e.g. dibutyl phthalate (DBP)). We identify a novel repressor mechanism that explains this vulnerabil...

Reproduction is our biological reason for being. Evolution has shaped us via countless millennia with this one purpose in mind. Our development from an early embryo through to adulthood is geared to making us fit to reproduce, a process that is closely connected to nutrition and energy stores. Seasonal and other fluctuations in food supply has been a key evolutionary shaper of the reproductive process, as illustrated by seasonal breeding species. Humans have echoes of this sea...

Reproduction is our biological reason for being. Evolution has shaped us via countless millennia with this one purpose in mind. Our development from an early embryo through to adulthood is geared to making us fit to reproduce, a process that is closely connected to nutrition and energy stores. Seasonal and other fluctuations in food supply has been a key evolutionary shaper of the reproductive process, as illustrated by seasonal breeding species. Humans have echoes of this sea...

Background: Maternal high fat diet (HFD) exposure is thought to perturb offspring metabolism, however the literature on experimental animal studies is inconsistent.Objectives: (i) In experimental studies, appraise data regarding metabolic parameters in offspring of mothers who consumed a HFD, (ii) assess possible predictors for these, and (iii) explore the quality of the evidence base.Methods: Searches were performed in four electr...

Specific ablation of the androgen receptor (AR) in selected target cells prevents the major developmental defects inherent to generalised AR inactivation (Tfm, ARKO) and allows a detailed analysis of the contribution of defined cells and molecular pathways to more complex effects of androgens. We successfully applied this approach in the study of the role of androgens in the control of spermatogenesis, by developing a Cre/loxP-based mouse model with a Sertoli cell (SC)-selecti...

Spermatogenesis is a complex process involving interactions between the somatic cells (Sertoli, Leydig, peritubular) and germ cells within the adult testis. Androgens are key regulators of spermatogenesis and intra-testicular concentrations of testosterone (T), produced by the Leydig cells, are higher than that in blood. Androgen action is mediated by the androgen receptor (AR), an X-chromosome-encoded, ligand-activated, transcription factor. The mechanisms by which androgens ...

From human epidemiological and related studies, there is strong (indirect) evidence that common male reproductive disorders that manifest at birth (cryptorchidism, hypospadias) or in adulthood (low sperm count, low testosterone, primary hypogonadism) may have a common origin in foetal life due to impaired androgen (testosterone) production or action; the so-called testicular dysgenesis syndrome (TDS) hypothesis. Whilst the foetal origin of cryptorchidism and hypospadias is sel...

Background: 5-Cytosine methylation of DNA is a means of encoding epigenetic information. In the testis, the generation of de novo methylation is conducted by the enzymes DNMT3a and 3b and the co-enzyme DNMT3L. Epigenetic marks made to the DNA of germ cells are important as a potential means of trans-generational carriage of environmental information. In fetal life, germ cell demethylation and remethylation are important physiological events and these overlap with key ...

Testicular dysgenesis syndrome (TDS) is a group of associated conditions (testicular germ cell tumours (TGCT), cryptorchidism, hypospadias and low sperm counts) that are thought to have a common origin in fetal life. Exposure of fetal rats to environmental chemicals such as the endocrine disrupting chemical di(n-butyl) phthalate (DBP) results in a TDS-like syndrome. However, exposed rats do not develop TGCT and the rodent is a poor model in this context. The effects of ...