Androgen-dependent sertoli cell tight junction remodeling is mediated by multiple tight junction components.

Sertoli cell tight junctions (SCTJs) of the seminiferous epithelium create a specialized microenvironment in the testis to aid differentiation of spermatocytes and spermatids from spermatogonial stem cells. SCTJs must be chronically broken and rebuilt with high fidelity to allow the transmigration of preleptotene spermatocytes from the basal to adluminal epithelial compartment. Impairment of androgen signaling in Sertoli cells perturbs SCTJ remodeling.

Deregulated sex chromosome gene expression with male germ cell-specific loss of Dicer1.

MicroRNAs (miRNAs) are a class of endogenous, non-coding RNAs that mediate post-transcriptional gene silencing by inhibiting mRNA translation and promoting mRNA decay. DICER1, an RNase III endonuclease encoded by Dicer1, is required for processing short 21-22 nucleotide miRNAs from longer double-stranded RNA precursors. Here, we investigate the loss of Dicer1 in mouse postnatal male germ cells to determine how disruptions in the miRNA biogenesis pathway may contribute to infertility.

The role of miR-506 in transformed 16HBE cells induced by anti-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide.

Growing evidence indicates that the alteration of microRNA (miRNA) expression in tumors that is induced by chemical carcinogens plays an important role in tumor development and progression. However, the mechanism underlying miRNA involvement in lung carcinogenesis induced by anti-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide (anti-BPDE) remains unclear. In our study, we used the malignant transformation of human bronchial epithelial cells (16HBE-T) induced by anti-BPDE to explore the mechanisms of human lung carcinogenesis.

Low-level expression of let-7a in gastric cancer and its involvement in tumorigenesis by targeting RAB40C.

Gastric cancer is the fourth most common cancer and the second leading cause of cancer mortality worldwide but the underlying molecular mechanism is not entirely clear. The objective of this study was to explore the role of let-7a microRNA (miRNA) in gastric tumorigenesis and the possible correlation between RAB40C and let-7a miRNA in gastric cancer. We found that expression of let-7a is reduced in human gastric cancer tissues and cell lines and there was a significant correlation between the level of let-7a expression and the stage of differentiation.

miR-106a-mediated malignant transformation of cells induced by anti-benzo[a]pyrene-trans-7,8-diol-9,10-epoxide.

microRNAs (miRNAs) are an abundant class of small noncoding RNAs that function primarily as oncogenes and tumor suppressors by mediating translational repression or mRNA degradation via binding target genes. In this study, malignant human bronchial epithelial cells transformed by anti-benzo[a]pyrene-trans-7,8-diol-9,10-epoxide were used to help characterize the possible mechanisms of miRNA function in chemical carcinogenesis. The expression level of miR-106a was measured by the real-time, reverse transcriptase polymerase chain reaction.

miR-22 functions as a micro-oncogene in transformed human bronchial epithelial cells induced by anti-benzo[a]pyrene-7,8-diol-9,10-epoxide.

MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively control the expression of target genes post-transcriptionally. In this study, transformed human bronchial epithelial cells induced by anti-benzo[a]pyrene-7,8-diol-9,10-epoxide were characterized for miRNA involved in carcinogenesis. We found miR-22, which was highly expressed in transformed cells, concomitant with downregulation of the tumour suppressor gene PTEN protein.

Overexpressed miR-494 down-regulates PTEN gene expression in cells transformed by anti-benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide.

Aims: We investigated the functionality of miR-494 in anti-benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide (anti-BPDE)-transformed human bronchial epithelial cell 16HBE to reveal its potential target coding-gene.

Main Methods: The expression of mature miR-494 in cells was detected by miRNA-specific quantitative real-time polymerase chain reaction (QRT-PCR). QRT-PCR and Western blot were used to identify the expression of phosphatase and tensin homolog (PTEN) mRNA and protein.

MicroRNA expression profiles and miR-10a target in anti-benzo[a] pyrene-7, 8-diol-9, 10-epoxide-transformed human 16HBE cells.

Objective: To screen miRNA profiles of malignantly transformed human bronchial epithelial cells, 16HBE-T, induced by anti-benzo[a]pyrene-trans-7,8-diol-9,10-epoxide (anti-BPDE), and to analyze putative miR-10a targets in 16HBE-T.

Methods: A novel microarray platform was employed to screen miRNA profiles of 16HBE-T cells transformed by anti-BPDE. Microarray data for miR-10a and miR-320 were validated using quantitative real time polymerase chain reaction (QRT-PCR).

Effects of silencing of HER2/neu gene in anti-BPDE-transformed cells.

Anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE) is a metabolite of benzo[a]pyrene (B[a]P) and acts as a potent mutagen in mammalian systems. However, the molecular mechanisms related to anti-BPDE-induced carcinogenesis are poorly understood. We have used malignant human bronchial epithelial cells (16HBE-T) transformed by exposure to anti-BPDE to help characterize these possible molecular mechanisms.

Silencing of N-Ras gene expression using shRNA decreases transformation efficiency and tumor growth in transformed cells induced by anti-BPDE.

Anti-benzo[a]pyrene-trans-7,8-diol-9,10-epoxide (anti-BPDE) is the most important metabolite of benzo[a]pyrene which is a ubiquitous environmental pollutant, and may cause human cancer, especially of the lung. Ras genes (H, K, and N) are activated in 40% of human tumors and may contribute to carcinogenesis. Here, we used malignant human bronchial epithelial cells transformed by anti-BPDE (16HBE-T) to help characterize possible molecular mechanisms of carcinogenesis.

Paraquat toxicity in a mouse embryonic stem cell model.

The objective of this in vitro study was to use a mouse embryonic stem (mES) cell model to better understand pesticide injury that may adversely affect early pregnancy and to evaluate an antioxidant intervention. Undifferentiated D3 mES cells were incubated 24h with control, reference dose (RfD), no observed effect level (NOEL), or lowest observed effect level (LOEL) of paraquat, a commonly used, toxic agricultural herbicide. Pesticide effects were evaluated at 0 and 24h using assays for cell proliferation, total reactive oxygen species (ROS), viability, and alkaline phosphatase activity.

Genotyping Parkinson disease-associated mitochondrial polymorphisms.

Objective: The purpose of this study was to establish a system for rapidly detecting single nucleotide polymorphisms (SNPs) in mitochondrial DNA (mtDNA) using hybridization probes and melting temperature (T(m)) analysis. This technology should prove useful for population-based studies on the interaction between genetic factors and environmental exposures and the risk of Parkinson disease (PD).

Methods: Mitochondrial DNA (mtDNA) was extracted from whole blood.

Congenital and idiopathic scoliosis: clinical and genetic aspects.

Objective: Genetic and environmental factors influencing spinal development in lower vertebrates are likely to play a role in the abnormalities associated with human congenital scoliosis (CS) and idiopathic scoliosis (IS). An overview of the molecular embryology of spinal development and the clinical and genetic aspects of CS and IS are presented. Utilizing synteny analysis of the mouse and human genetic databases, likely candidate genes for human CS and IS were identified.

Pregnancy outcomes for mouse preimplantation embryos exposed in vitro to the estrogenic pesticide o,p'-DDT.

Pregnancy outcomes were evaluated following uterine transfer of murine preimplantation embryos exposed in vitro to the estrogenic pesticide o,p'-dichlorodiphenyltrichloroethane (o,p'-DDT). Single-cell embryos were incubated 72 h in medium droplets containing 0.1% ethanol (control) or 0.

Low-dose agrochemicals and lawn-care pesticides induce developmental toxicity in murine preimplantation embryos.

Occupational exposures to pesticides may increase parental risk of infertility and adverse pregnancy outcomes such as spontaneous abortion, preterm delivery, and congenital anomalies. Less is known about residential use of pesticides and the risks they pose to reproduction and development. In the present study we evaluate environmentally relevant, low-dose exposures to agrochemicals and lawn-care pesticides for their direct effects on mouse preimplantation embryo development, a period corresponding to the first 5-7 days after human conception.

Risk factors for female infertility in an agricultural region.

Background: Recent studies have suggested that agricultural occupations or exposure to pesticides may impair female fertility.

Methods: The Fertility Risk Factor Study retrospectively examined agricultural and residential exposures and the risk of female infertility. Cases and controls (N = 322 each) came from women who sought treatment at a large group medical clinic in Wisconsin.