Phthalates are widely used plasticizers recognized as endocrine-disrupting chemicals (EDCs) with well-documented adverse effects on reproductive health. These compounds act either directly or through their metabolites and can influence various biochemical pathways. Key phthalates that have been associated with potential toxic outcomes include di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), butyl benzyl phthalate (BBP), diisononyl phthalate (DiNP), and diisodecyl phthalate (DiDP). The presence of these compounds in everyday consumer products has been associated with various adverse effects on human reproductive health, including hormonal disruption, issues in gonadal function, and other hormone related problems. This systematic review provides an overview and critical synthesis of the most recent research regarding phthalate reproductive toxicity. The scope is to summarize and aggregate correlations between phthalate exposure and reproductive health outcomes and highlight factors, such as age, sex, and extent of exposure, that have the most significant impacts on clinical outcomes. The reported studies focus on the gender-specific outcomes of various phthalates, while the epidemiological data reveal the importance of exposure duration and age. The reported results highlight the need for strict regulations regarding phthalate usage and the importance of developing safer alternatives.

Mantle cell lymphoma (MCL) is a rare, aggressive B-cell neoplasm that frequently relapses and only shows a limited response to conventional chemotherapy. A major challenge in MCL research is culturing primary MCL cells ex vivo, as cells tend to undergo spontaneous apoptosis when cultured in 2D suspension culture. Although 3D models are known to better recapitulate the in vivo situation of solid tumors, their application is still poorly explored in lymphomas. Developing 3D models that replicate the in vivo conditions of MCL within the lymph node could enhance their survival, facilitate the study of the MCL-tumor microenvironment crosstalk, and mimic the in vivo drug response. Here, a 3D printed model of MCL in the form of hydrogel tumor slices was established, along with an optimized culture method. A standardized process was developed using MCL cell lines or primary MCL cells, in which the cells are immersed in a hydrogel containing alginate, type I collagen, and basement membrane matrix by bioprinting into a gelatin support bath. The resulting MCL hydrogel tumor slices are cultured on a filter support to maintain their stability throughout the culture period. Drug treatments can be applied to the system. The response of single cells inside the hydrogel tumor slice can be tracked by four-color live 3D fluorescence imaging. Primary MCL cells demonstrated a stable viability when cultured in the hydrogel tumor slices. This protocol provides a detailed description of the generation, culture, and analysis of MCL cells in hydrogel tumor slices. By closely mimicking the tumor microenvironment and utilizing an air-liquid interface culture, the presented model enhances physiological relevance compared to the traditional 2D culture. It offers significant potential for advancing both biological and therapeutic studies of MCL.

Mantle cell lymphoma (MCL) is a rare, aggressive B-cell neoplasm that frequently relapses and only shows a limited response to conventional chemotherapy. A major challenge in MCL research is culturing primary MCL cells ex vivo, as cells tend to undergo spontaneous apoptosis when cultured in 2D suspension culture. Although 3D models are known to better recapitulate the in vivo situation of solid tumors, their application is still poorly explored in lymphomas. Developing 3D models that replicate the in vivo conditions of MCL within the lymph node could enhance their survival, facilitate the study of the MCL-tumor microenvironment crosstalk, and mimic the in vivo drug response. Here, a 3D printed model of MCL in the form of hydrogel tumor slices was established, along with an optimized culture method. A standardized process was developed using MCL cell lines or primary MCL cells, in which the cells are immersed in a hydrogel containing alginate, type I collagen, and basement membrane matrix by bioprinting into a gelatin support bath. The resulting MCL hydrogel tumor slices are cultured on a filter support to maintain their stability throughout the culture period. Drug treatments can be applied to the system. The response of single cells inside the hydrogel tumor slice can be tracked by four-color live 3D fluorescence imaging. Primary MCL cells demonstrated a stable viability when cultured in the hydrogel tumor slices. This protocol provides a detailed description of the generation, culture, and analysis of MCL cells in hydrogel tumor slices. By closely mimicking the tumor microenvironment and utilizing an air-liquid interface culture, the presented model enhances physiological relevance compared to the traditional 2D culture. It offers significant potential for advancing both biological and therapeutic studies of MCL.