Effects of continuous bisphenol A exposure from early gestation on 90 day old rat testes function and sperm molecular profiles: A CLARITY-BPA consortium study.

Bisphenol A (BPA) is a ubiquitous industrial chemical that has been identified as an endocrine disrupting compound (EDC). There is growing concern that early life exposures to EDCs, such as BPA, can adversely affect the male reproductive tract and function. This study was conducted as part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA) to further delineate the toxicities associated with continuous exposure to BPA from early gestation, and to comprehensively examine the elicited effects on testes and sperm.

From the Cover: Sperm Molecular Biomarkers Are Sensitive Indicators of Testicular Injury following Subchronic Model Toxicant Exposure.

Traditional testis histopathology endpoints remain the gold standard for evaluating testicular insult and injury in a non-clinical setting, but are invasive and unfeasible for monitoring these effects clinically in humans. Assessing testicular injury in humans relies on semen and serum hormone analyses, both of which are insensitive and poor indicators of effect. Therefore, we hypothesized that sperm messenger RNA (mRNA) transcripts and DNA methylation marks can be used as translatable and sensitive indicators or testicular injury.

Biomarkers of chemotherapy-induced testicular damage.

Increasing numbers of men are having or wanting children after chemotherapy treatment. This can be attributed to improvements in cancer therapies that increase survival. However, a side effect of most chemotherapy drugs is disruption of spermatogenesis and a drastic reduction in sperm count and quality.

SOT Symposium Highlight: Translatable Indicators of Testicular Toxicity: Inhibin B, MicroRNAs, and Sperm Signatures.

Testicular toxicity is an important safety endpoint in drug development and risk assessment, but reliable and translatable biomarkers for predicting injury have eluded researchers. However, this area shows great potential for improvement, with several avenues currently being pursued. This was the topic of a symposium session during the 2013 Society of Toxicology Annual Meeting in San Antonio, TX, entitled "Translatable Indicators of Testicular Toxicity: Inhibin B, MicroRNAs, and Sperm Signatures.

The current status of biomarkers for predicting toxicity.

Introduction: There are significant rates of attrition in drug development. A number of compounds fail to progress past preclinical development due to limited tools that accurately monitor toxicity in preclinical studies and in the clinic. Research has focused on improving tools for the detection of organ-specific toxicity through the identification and characterization of biomarkers of toxicity.

Sperm mRNA transcripts are indicators of sub-chronic low dose testicular injury in the Fischer 344 rat.

Current human reproductive risk assessment methods rely on semen and serum hormone analyses, which are not easily comparable to the histopathological endpoints and mating studies used in animal testing. Because of these limitations, there is a need to develop universal evaluations that reliably reflect male reproductive function. We hypothesized that toxicant-induced testicular injury can be detected in sperm using mRNA transcripts as indicators of insult.

Optimization of a filter-lysis protocol to purify rat testicular homogenates for automated spermatid counting.

Quantifying testicular homogenization-resistant spermatid heads (HRSH) is a powerful indicator of spermatogenesis. These counts have traditionally been performed manually using a hemocytometer, but this method can be time consuming and biased. We aimed to develop a protocol to reduce debris for the application of automated counting, which would allow for efficient and unbiased quantification of rat HRSH.

Multicomponent folate-targeted magnetoliposomes: design, characterization, and cellular uptake.

Unlabelled: Folate-targeted cationic magnetoliposomes (FTMLs) have been prepared with coencapsulated doxorubicin (DOX) and anionic superparamagnetic iron oxide (SPIO) nanoparticles (NPs) with 5 nm γ-Fe(2)O(3) cores and 16 nm hydrodynamic diameters. NP encapsulation (89%) was confirmed by cryogenic transmission electron microscopy (TEM), and the presence of the oppositely charged NPs did not cause liposome aggregation. The FTMLs had an average diameter of 174 ± 53 nm and existed as unilamellar and cup-shaped liposomes, which was attributed to dissimilar lipid packing parameters and the presence of PEG-lipids.

Modulation of constitutive androstane receptor (CAR) and pregnane X receptor (PXR) by 6-arylpyrrolo[2,1-d][1,5]benzothiazepine derivatives, ligands of peripheral benzodiazepine receptor (PBR).

Constitutive androstane receptor (CAR) and pregnane X receptor (PXR) regulate xenobiotic sensing and metabolism through interactions with multiple exogenous and endogenous chemicals. Compounds that activate CAR are often ligands of PXR; attention is therefore given to discovery of new, receptor-specific chemical entities that may be exploited for therapeutic and basic research purposes. Recently, ligands of the peripheral benzodiazepine receptor (PBR), PK11195 and FGIN-1-27, were shown to modulate both CAR and PXR.

Rational quantitative structure-activity relationship (RQSAR) screen for PXR and CAR isoform-specific nuclear receptor ligands.

Constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are closely related orphan nuclear receptor proteins that share several ligands and target overlapping sets of genes involved in homeostasis and all phases of drug metabolism. CAR and PXR are involved in the development of certain diseases, including diabetes, metabolic syndrome and obesity. Ligand screens for these receptors so far have typically focused on steroid hormone analogs with pharmacophore-based approaches, only to find relatively few new hits.

Subfertility caused by altered follicular development and oocyte growth in female mice lacking PKB alpha/Akt1.

Mammalian females are endowed with a finite number of primordial follicles at birth. Immediately following formation of the primordial follicle pool, cohorts of follicles are either culled from the ovary or are recruited to grow until the primordial follicle population is depleted. The majority of ovarian follicles, including the oocytes, undergo atresia through apoptotic cell death.