Unveiling the intricacies of BPA and BPS: Comprehensive insights into its toxic effects using a cutting-edge microphysiological system.

Concerns over Bisphenol A (BPA) and its substitute, Bisphenol S (BPS), have led to innovative exploration due to potential adverse health effects. BPS, replacing BPA in some regions to avoid toxic impacts, remains insufficiently studied. Besides this, the organ-on-a-chip technology emerges as a transformative solution in drug discovery and chemiclas toxicity testing, minimizing costs and aligning with ethical standards by reducing reliance on animal models, by integrating diverse tissues and dynamic cell environments enhances precision in predicting organ function. Here, we employ a 3-organ-on-a-chip microfluidic device with skin, intestine, and liver cultures to assess the effects of BPA and BPS via topical and oral administration. Our evaluation focused on gene markers associated with carcinogenicity, systemic toxicity, and endocrine disruption. BPA exhibited expected absorption profiles, causing liver injury and genetic modulation in related pathways. BPS, a safer alternative, induced adverse effects on gene expression, particularly in topical absorption, with distinct absorption patterns. Our findings underscore the urgency of addressing BPA and BPS toxicity concerns, highlighting the crucial role of organ-on-a-chip technology in understanding associated health risks. The study promotes the organ-on-a-chip methodology as a valuable tool for safe drug development and disease treatments, offering a novel liver toxicity screening alternative to traditional animal tests. This contributes to advancing comprehension of the biological effects of these compounds, fostering improved safety assessments in human health.

Combining a microphysiological system of three organ equivalents and transcriptomics to assess toxicological endpoints for cosmetic ingredients.

Animal testing for cosmetic ingredients and final products has been banned in Europe and is gaining legal force worldwide. However, the need for reliable testing methodologies remains for safety assessment of cosmetic ingredients. While new approach methodologies exist for many toxicological endpoints, some complex ones lack appropriate testing methods. Microphysiological systems (MPSs) have emerged as a promising tool to address this gap in pre-clinical testing, offering higher predictivity compared to animal models due to the phylogenetic distance between humans and animals. Moreover, they provide a more physiological approach than traditional in vitro testing by mimicking interconnections between different culture compartments as seen in complex organisms. This study presents a three-organ microfluidic MPS comprising skin, liver, and intestine equivalents. Combining this model with gene expression analysis, we evaluated toxicological endpoints of chemicals, demonstrating its potential for diverse applications. Our findings highlight the MPS model as a reliable and ethical method to be applied in an integrated approach for safety assessment in the cosmetic industry. It offers a promising strategy to evaluate toxicological endpoints for cosmetic ingredients and other chemicals, supporting the elimination of animal testing while ensuring consumer safety.

Albumin is synthesized in epididymis and aggregates in a high molecular mass glycoprotein complex involved in sperm-egg fertilization.

The epididymis has an important role in the maturation of sperm for fertilization, but little is known about the epididymal molecules involved in sperm modifications during this process. We have previously described the expression pattern for an antigen in epididymal epithelial cells that reacts with the monoclonal antibody (mAb) TRA 54. Immunohistochemical and immunoblotting analyses suggest that the epitope of the epididymal antigen probably involves a sugar moiety that is released into the epididymal lumen in an androgen-dependent manner and subsequently binds to luminal sperm. Using column chromatography, SDS-PAGE with in situ digestion and mass spectrometry, we have identified the protein recognized by mAb TRA 54 in mouse epididymal epithelial cells. The ∼65 kDa protein is part of a high molecular mass complex (∼260 kDa) that is also present in the sperm acrosomal vesicle and is completely released after the acrosomal reaction. The amino acid sequence of the protein corresponded to that of albumin. Immunoprecipitates with anti-albumin antibody contained the antigen recognized by mAb TRA 54, indicating that the epididymal molecule recognized by mAb TRA 54 is albumin. RT-PCR detected albumin mRNA in the epididymis and fertilization assays in vitro showed that the glycoprotein complex containing albumin was involved in the ability of sperm to recognize and penetrate the egg zona pellucida. Together, these results indicate that epididymal-derived albumin participates in the formation of a high molecular mass glycoprotein complex that has an important role in egg fertilization.

Orchidopexy restores morphometric-stereologic changes in the caput epididymis and daily sperm production in cryptorchidic mice, although sperm transit time and fertility parameters remain impaired.

OBJECTIVE: To evaluate the changes in the caput epididymis following cryptorchidism and orchidopexy. DESIGN: Experimental study in a research laboratory. SETTING: Reproductive biology research laboratory. ANIMAL(S): Immature male and mature female mice (C57BL/6). INTERVENTION(S): Experimental cryptorchidism and orchidopexy. MAIN OUTCOME MEASURE(S): Morphometric-stereologic analyses, serum testosterone dosage, immunohistochemical staining of the antigen TRA54 (testicular germ cells immunized to a rat monoclonal antibody), smooth muscle α-actin (SM α-actin) and SM myosin heavy chain, sperm transit time, and fertility parameters. RESULT(S): There was a significant reduction in the morphometric-stereologic parameters in the cryptorchidic mice. These parameters demonstrated significant recovery following orchidopexy. Staining for an androgen-dependent antigen, TRA54, was observed in all groups. SM α-actin and SM myosin heavy chain staining was significantly increased in the cryptorchidism group but stable in the orchidopexy group. Despite the recovery of daily sperm production in the testes, the sperm transit time in the epididymis and fertility parameters remained significantly reduced in the orchidopexy group. CONCLUSION(S): In cryptorchidic animals, there was an acceleration of sperm passage through the epididymal duct. Orchidopexy did not restore the normal passage time. Accordingly, there was a significant reduction in the fertility parameters in the cryptorchidic group that were not fully recovered following orchidopexy.

OSP-Immunofluorescent remyelinating oligodendrocytes in the brainstem of toxically-demyelinated Wistar rats.

Central nervous system (CNS) remyelination following toxically-induced demyelination is a well known process. Oligodendrocytes constitute the bulk of the myelinating cells in the brain whereas Schwann cells overwhelm oligodendrocytes numbers in spinal cord remyelination. Despite the common knowledge of these facts, we still do not know completely the origin of both remyelinating cells. The present study investigated the participation of mature oligodendrocytes in remyelination after ethidium-bromide (EB) induced demyelination in the brainstem of normal and cyclosporin A-immunosuppressed Wistar rats. Thirty adult female rats were divided into three experimental groups. In group 1 the rats received a single intracisternal injection of 10 microL of 0.1% ethidium bromide (EB) in 0.9% saline (n=10); in group 2 the rats received the EB injection while immunosuppressed with cyclosporin A (n=10); in group 3 the rats received a single 10 microL injection of 0.9% saline while treated with cyclosporin A. The rats were killed at 15, 21 and 31 days after injection. Within the EB lesions, from 15 days onward many cells within the periphery of the lesions stained positive for OSP (oligodendrocyte specific protein) a marker for mature oligodendrocytes and myelin. This cell marking signals that, at least, part of the process of repairing the myelin sheaths is carried out by mature cells of the oligodendrocyte lineage.

OSP-Immunofluorescent remyelinating oligodendrocytes in the brainstem of toxically-demyelinated Wistar rats

A remielinização do sistema nervoso central após desmielinização tóxica é um processo bem conhecido. No encéfalo, os oligodendrócitos remielinizam uma área maior do que na medula espinhal, onde as células de Schwann são preponderantes. Embora esses fatos sejam bem conhecidos, ainda não se conhece com certeza a origem das células remielinizantes. Esta investigação foi desenhada para esclarecer a participação de oligodendrócitos maduros na reconstrução das bainhas perdidas após a desmielinização induzida por brometo de etídio (BE) no tronco encefálico de ratos Wistar normais e imunossuprimidos com ciclosporina A. Trinta ratos fêmeas adultas foram divididos em três grupos experimentais. No grupo 1, os ratos receberam uma injeção de 10 mL de BE em 0,9% salina (n=10) na cisterna basal; no grupo 2, os ratos receberam a injeção de BE e foram tratados com ciclosporina A (n=10); no grupo 3 os ratos receberam uma injeção de 10 mL de 0,9% salina e foram tratados com ciclosporina A. Os ratos foram sacrificados aos 15, 21 e 31 dias após a injeção. A partir dos 15 dias muitas células da periferia das lesões tiveram marcação positiva para OSP (proteína específica do oligodendrócito), marcador de oligodendrócitos maduros e mielina. Assim, foi possível comprovar que células maduras da linhagem oligodendroglial participam do processo de remielinização neste modelo gliotóxico.