Abnormal histology in testis from prepubertal boys with monorchidism.

BACKGROUND: Little is known about the histology of contralateral descended testes in boys with unilaterally absent testis. We investigated whether absence of one testis is associated with abnormal tissue architecture of the solitary contralaterally descended testis. DESIGN SETTING AND PATIENTS: For this retrospective study, we examined the results of biopsies of the contralateral descended testis in 43 boys with monorchidism. Data from 26 control testes from boys of matching ages were selected from results published in 1977 and 2009. During surgery, any nubbins were removed. In each case, the scrotal testis was biopsied, and the testis fixed by subdartos pouch or suture. RESULTS: Of the 43 affected boys, 23 had normal testicular histology in the contralateral descended testis, whereas 20 (46%) had abnormal histology. Eight of the abnormal biopsies matched the criteria for high infertility risk. Samples from three boys in this latter group revealed a Sertoli-cell-only phenotype. Immunohistochemical assays were positive for steroidogenic acute regulatory (STAR) protein in Leydig cells and spermatogonia. STAR expression was stronger in the monorchid group with normal testicular histology. CONCLUSIONS: Almost half of the patients with unilateral absent testis were at risk for subfertility or infertility. Our results emphasize the need for testicular biopsy of the solitary testis in boys with monorchidism to appropriately assess infertility risk.

CONTEXTE: Peux d'études ont analysé la structure des tissus testiculaires des testicules descendus controlatéraux chez les garçons avec des testicules unilatéraux absents. Nous avons investigué si l'absence congénitale d'un testicule est. associée à une histologie anormale des testicules descendus controlatéraux solitaires. CONCEPTION CONTEXTE ET PATIENTS: Cette étude rétrospective a examiné les résultats des biopsies des testicules descendus controlatéraux de 43 garçons monorchides. Les données de 26 testicules témoins ont été appariées surl'âge et sélectionnées à partir des données publiées en 1977 et 2009. Pendant l'opération, les nubins (reliquats) détectés ont été enlevés. Dans chaque cas, les testicules scrotaux ont fait l'objet d'une biopsie et d'une fixation par la technique de la valise ou par suture au subdartos. RÉSULTATS: Parmi 43 garçons, 23 avaient une histologie testiculaire normale dans les testicules descendus controlatéraux, tandis que 20 (46%) avaient une histologie anormale. Huit biopsies anormales correspondaient aux critères de risque élevé d'infertilité. Trois garçons de ce groupe avaient une histologie testiculaire montrant la présence de cellules Sertoli seules. L'analyse immunohistochimique de la protéine STAR a montré un signale dans les cellules de Leydig et dans les spermatogonies. L'expression STAR était plus forte dans le groupe des monorchides avec une histologie testiculaire normale. CONCLUSIONS: Près de la moitié des patients ayant des testicules congénitaux unilatéraux absents couraient un risque d'hypofertilité ou d'infertilité. Nos résultats soulignent la nécessité d'une biopsie testiculaire des testicules solitaires chez les garçons monorchides afin d'évaluer le risque d'infertilité de ces patients.

Piwi-pathway alteration induces LINE-1 transposon derepression and infertility development in cryptorchidism.

Spermatogonia contain processing bodies that harbor P-element-induced wimpy testis (Piwi) proteins. Piwi proteins are associated specifically with Piwi-interacting RNAs to silence transposable DNA elements. Loss-of-function mutations in the Piwi pathway lead to derepression of transposable elements, resulting in defective spermatogenesis. Furthermore, deletion of gametocyte-specific factor 1 (GTSF1), a factor involved in Piwi-mediated transcriptional repression, causes male-specific sterility and derepression of LINE-1 (L1) retrotransposons. No previous studies have examined GTSF1, L1 and PIWIL4 expression in cryptorchidism. We examined transposon-silencing genes and L1 transposon expression in testicular biopsies with Affymetrix microarrays and immunohistology. Seven members of the Tudor gene family, 3 members of the DEAD-box RNA helicase family, and the GTSF1 gene were found to show significantly lower RNA signals in the high-infertility-risk group. In the immunohistochemical analysis, patients from the low-infertility-risk group showed coherently stronger staining for GTSF1 and PIWIL4 proteins and weaker staining for L1 transposon when compared to the high-infertility-risk samples. These new findings provide first evidence consistent with the idea that infertility in cryptorchidism is a consequence of alterations in the Piwi pathway and transposon derepression induced by the impaired function of mini-puberty.

The effect of hypophysectomy on pancreatic islet hormone and insulin-like growth factor I content and mRNA expression in rat.

The growth arrest after hypophysectomy in rats is mainly due to growth hormone (GH) deficiency because replacement of GH or insulin-like growth factor (IGF) I, the mediator of GH action, leads to resumption of growth despite the lack of other pituitary hormones. Hypophysectomized (hypox) rats have, therefore, often been used to study metabolic consequences of GH deficiency and its effects on tissues concerned with growth. The present study was undertaken to assess the effects of hypophysectomy on the serum and pancreatic levels of the three major islet hormones insulin, glucagon, and somatostatin, as well as on IGF-I. Immunohistochemistry (IHC), in situ hybridization (ISH), radioimmunoassays (RIA), and Northern blot analysis were used to localize and quantify the hormones in the pancreas at the peptide and mRNA levels. IHC showed slightly decreased insulin levels in the beta cells of hypox compared with normal, age-matched rats whereas glucagon in alpha cells and somatostatin in delta cells showed increase. IGF-I, which localized to alpha cells, showed decrease. ISH detected a slightly higher expression of insulin mRNA and markedly stronger signals for glucagon and somatostatin mRNA in the islets of hypox rats. Serum glucose concentrations did not differ between the two groups although serum insulin and C-peptide were lower and serum glucagon was higher in the hypox animals. These changes were accompanied by a more than tenfold drop in serum IGF-I. The pancreatic insulin content per gram of tissue was not significantly different in hypox and normal rats. Pancreatic glucagon and somatostatin per gram of tissue were higher in the hypox animals. The pancreatic IGF-I content of hypox rats was significantly reduced. Northern blot analysis gave a 2.6-, 4.5-, and 2.2-fold increase in pancreatic insulin, glucagon, and somatostatin mRNA levels, respectively, in hypox rats, and a 2.3-fold decrease in IGF-I mRNA levels. Our results show that the fall of serum IGF-I after hypophysectomy is accompanied by a decrease in pancreatic IGF-I peptide and mRNA but by partly discordant changes in the serum concentrations of insulin and glucagon and the islet peptide and/or mRNA content of the three major islet hormones. It appears that GH deficiency resulting in a "low IGF-I state" affects translational efficiency of these hormones as well as their secretory responses. The maintenance of normoglycemia in the presence of reduced insulin and elevated glucagon serum levels, both of which would be expected to raise blood glucose, may result mainly from the enhanced insulin sensitivity, possibly due to GH deficiency and the subsequent decrease in IGF-I production.