Molecular Characterization of Patients with Cryptorchidism: Preliminary Search for an Expression Profile Related to That of Testicular Germ-Cell Tumors.

Cryptorchidism (CO) is a risk factor for the development of testicular germ-cell tumors (TGCT). This is supported by reports showing the persistence of gonocytes in CO patients. These cells are proposed to be related to the development of germ-cell neoplasia in situ (GCNIS), which is considered the precursor stage/lesion of TGCT. Therefore, it is proposed that some patients with CO could express some molecular markers related to TGCT. In this study, we analyzed testicular tissue samples from CO, TGCT, and controls. We determined the expression of POU5F1, PLAP, and KIT by immunohistochemistry and that of the hsa-miR-371-373 cluster, hsa-miR-367, and LATS2, PTEN, and IGFR1 genes by RT-qPCR. We then carried out a bioinformatic analysis to identify other possible candidate genes as tumor biomarkers. We found that 16.7% (2/12) of the CO patients presented increased expression of POU5F1, KIT, PLAP, hsa-miR-371-373, and hsa-miR-367 and decreased expression of LATS2 and IGF1R. Finally, the genes ARID4B, GALNT3, and KPNA6 were identified as other possible candidate tumor biomarkers. This is the first report describing the expression of the hsa-miR-371-373 cluster, hsa-miR-367, LATS2, and IGF1R in the testicular tissues of two CO patients with cells immune-positive to POU5F1, PLAP, and KIT, which is similar to what is observed in TGCT.

The Role of microRNAs in the Gonocyte Theory as Target of Malignancy: Looking for Potential Diagnostic Biomarkers.

Some pediatric patients with cryptorchidism preserve cells with gonocyte characteristics beyond their differentiation period, which could support the theory of the gonocyte as a target for malignancy in the development of testicular neoplasia. One of the key molecules in gonocyte malignancy is represented by microRNAs (miRNAs). The goal of this review is to give an overview of miRNAs, a class of small non-coding RNAs that participate in the regulation of gene expression. We also aim to review the crucial role of several miRNAs that have been further described in the regulation of gonocyte differentiation to spermatogonia, which, when transformed, could give rise to germ cell neoplasia in situ, a precursor lesion to testicular germ cell tumors. Finally, the potential use of miRNAs as diagnostic and prognostic biomarkers in testicular neoplasia is addressed, due to their specificity and sensitivity compared to conventional markers, as well as their applications in therapeutics.

miRNAs: A potentially valuable tool in pesticide toxicology assessment-current experimental and epidemiological data review.

miRNAs are responsible for the regulation of many cellular processes such as development, cell differentiation, proliferation, apoptosis, and tumor growth. Several studies showed that they can also serve as specific, stable, and sensitive markers of chemical exposure. In this review, current experimental and epidemiological data evidencing deregulation in miRNA expression in response to fungicides, insecticides or herbicides were analyzed. As shown by Venn's diagrams, miR-363 and miR-9 deregulation is associated with fungicide exposure in vitro and in vivo, while let-7, miR-155, miR-181 and miR-21 were found to be commonly deregulated by at least three different insecticides. Furthermore, let-7, miR-30, miR-126, miR-181 and miR-320 were commonly deregulated by 3 different herbicides. Notably, these 5 miRNAs were also found to be deregulated by one or more insecticides, suggesting their participation in the cellular response to pesticides, regardless of their chemical structure. All these miRNAs have been proposed as potential biomarkers for fungicide, insecticide, or herbicide exposure. These results allow us to improve our understanding of the molecular mechanisms of toxicity upon pesticide exposure, although further studies are needed to confirm these miRNAs as definitive (not potential) biomarkers of pesticide exposure.