Methylation profiling of choroid plexus tumors reveals 3 clinically distinct subgroups.

Background: Choroid plexus tumors are intraventricular neoplasms derived from the choroid plexus epithelium. A better knowledge of molecular factors involved in choroid plexus tumor biology may aid in identifying patients at risk for recurrence.

Methods: Methylation profiles were examined in 29 choroid plexus papillomas (CPPs, WHO grade I), 32 atypical choroid plexus papillomas (aCPPs, WHO grade II), and 31 choroid plexus carcinomas (CPCs, WHO grade III) by Illumina Infinium HumanMethylation450 Bead Chip Array.

High-resolution genomic analysis does not qualify atypical plexus papilloma as a separate entity among choroid plexus tumors.

Choroid plexus tumors are rare neoplasms that mainly affect children. They include papillomas, atypical papillomas, and carcinomas. Detailed genetic studies are rare, and information about their molecular pathogenesis is limited.

Choroid plexus carcinomas are characterized by complex chromosomal alterations related to patient age and prognosis.

Choroid plexus carcinoma is a malignant brain tumor predominantly occurring in young children. Only limited data are available regarding the underlying molecular genetic alterations. Therefore, molecular inversion probe single nucleotide polymorphism (MIP SNP) arrays were performed on a series of 26 neuropathologically well-characterized choroid plexus carcinomas.

Insulin-like factor 3 levels in cord blood and serum from children: effects of age, postnatal hypothalamic-pituitary-gonadal axis activation, and cryptorchidism.

Context: The Leydig cell hormone insulin-like factor 3 (INSL3) is important for testicular descent. Currently INSL3 levels in cord blood, in serum throughout childhood, and in relation to congenital cryptorchidism are unknown.

Objective: The objective of the study was to characterize INSL3 levels in cord blood during the postnatal activation of the hypothalamic-pituitary-gonadal axis and in later childhood in normal boys and girls and cryptorchid boys.

Cellular origins of testicular dysgenesis in rats exposed in utero to di(n-butyl) phthalate.

Foetal exposure of male rats to di(n-butyl) phthalate (DBP) induces testicular changes similar to testicular dysgenesis syndrome in humans, including the formation of focal 'dysgenetic areas' within post-natal testes, surrounded by otherwise normal tubules exhibiting complete spermatogenesis. We hypothesize that these dysgenetic areas form when Sertoli (and other) cells are 'trapped' during the abnormal formation of large Leydig cell (LC) clusters in foetal life and by post-natal day (d) 4 these groups of intermingled cells attempt to form seminiferous tubules. It is likely that the malformed tubules resulting correspond to the dysgenetic areas evident in later life.

Expression of insulin-like factor 3 protein in the rat testis during fetal and postnatal development and in relation to cryptorchidism induced by in utero exposure to di (n-Butyl) phthalate.

Cryptorchidism is a common reproductive abnormality, possibly resulting from abnormal hormone production/action by the fetal testis. Insulin-like factor 3 (Insl3) is thought to be involved in gubernaculum development and transabdominal testicular descent, but its importance is unclear, due partly to lack of suitable Insl3 antibodies. We generated (by genetic immunization) and validated a novel antirat Insl3 antibody, which we used to characterize immunoexpression of Insl3 in rat Leydig cells (LCs) from fetal life until adulthood and its relationship to cryptorchidism.

Insulin-like factor 3: where are we now?

Insulin-like factor 3 (INSL3), previously known as the relaxin-like factor (RLF), is a major peptide hormone secreted from the testicular Leydig cells of adult men and circulating in the blood at a concentration of approximately 1 ng/mL. Women also produce INSL3 in the theca interna cells of ovarian follicles, but circulating levels remain below 100 pg/mL. INSL3 is structurally related to relaxin and insulin, but unlike the latter, signals through a novel G-protein-coupled receptor, LGR8.

Development and function of the adult generation of Leydig cells in mice with Sertoli cell-selective or total ablation of the androgen receptor.

It is established that androgens and unidentified Sertoli cell (SC)-derived factors can influence the development of adult Leydig cells (LC) in rodents, but the mechanisms are unclear. We evaluated adult LC development and function in SC-selective androgen receptor (AR) knockout (SCARKO) and complete AR knockout (ARKO) mice. In controls, LC number increased 26-fold and LC size increased by approximately 2-fold between 12 and 140 d of age.

The molecular basis of cryptorchidism.

Cryptorchidism is the commonest malady to affect newborn male infants. Until recently, the molecular aetiology of this syndrome was unclear. Cryptorchidism may be part of a broader testicular dysgenesis syndrome, wherein a disturbance in steroid hormone metabolism, possibly through a perturbed hypothalamic-pituitary-gonadal axis could be involved.