Although advances have been made in cancer therapy, cancer remains the second leading cause of death in the U.S. and Europe, and thus efforts to continue to study and discover better treatment ...methods are ongoing. Three-dimensional (3D) tumor models have shown advantages over bi-dimensional (2D) cultures in evaluating the efficacy of chemotherapy. This commentary aims to highlight the potential of combined application of biomaterials with patient-derived cancer cells as a 3D in vitro model for the study and treatment of cancer patients. Five studies were discussed which demonstrate and provided early evidence to create 3D models with accurate microenvironments that are comparable to in vivo tumors. To date, the use of patient-derived cells for a more personalized approach to healthcare in combination with biomaterials to create a 3D tumor is still relatively new and uncommon for application in clinics. Although highly promising, it is important to acknowledge the current limitations and challenges of developing these innovative in vitro models, including the need for biologists and laboratory technicians to become familiar with biomaterial scaffolds, and the effort for bioengineers to create easy-to-handle scaffolds for routine assessment.
Endocrine-disrupting chemical (EDC) exposures to the fetus have long-lasting effects on health and disease in adulthood. Such EDC exposure to the F1 fetuses also reaches the germ cells that become ...the F2 generation. Previously, we demonstrated that adult social and communicative behaviors such as ultrasonic vocalizations and mating behaviors were altered by EDCs in F2 rats, especially males. In the current study, we used the brains of these F2 males to ascertain the underlying molecular changes in the hypothalamus related to these behavioral outcomes. Their progenitors were Sprague-Dawley rat dams, treated on pregnancy days 8 to 18 with one of three treatments: a polychlorinated biphenyl (PCB) mixture, Aroclor 1221, selected because it is weakly estrogenic; the anti-androgenic fungicide vinclozolin (VIN); or the vehicle, 6% dimethylsulfoxide in sesame oil (VEH). In adulthood, F1 male and female offspring were bred with untreated partners to generate paternal or maternal lineages of the F2 offspring, the subjects of molecular work. Quantitative real-time PCR was conducted in the medial preoptic area (POA) and the ventromedial nucleus (VMN) of the hypothalamus, selected for their roles in social and sexual behaviors. Of the genes assessed, steroid hormone receptors (estrogen receptor α, androgen receptor, progesterone receptor) but not dopamine receptors 1 and 2 or DNA methyltransferase 3a expression were altered, particularly in the VIN males. Several significant correlations between behavior and gene expression were also detected. These results suggest that preconceptional exposure of male rats to EDCs at the germ cell stage alters the neuromolecular phenotype in adulthood in a lineage-dependent manner.
•EDC exposure effects are observed in male F2 descendants.•Gene expression of steroid hormone receptors were altered in the POA and VMN.•Vinclozolin (VIN) F2 males had higher POA Ar and Esr1 expression levels than controls.•In the VMN, VIN F2 males had significantly lower Esr1 and Pgr levels than controls.•Lineage (maternal, paternal) was a key determinant of the effects of EDCs.
Endocrine-disrupting chemicals (EDCs) can act upon a developing organism to change its endocrine health and behavior in adulthood. Beyond actions on the exposed individuals, transgenerational effects ...of several EDCs have been reported. This study assessed the combinatorial impact of EDC-altered maternal care and transgenerational inheritance on F3 male and female offspring. Pregnant rats were exposed to EDCs with different modes of action: the weakly estrogenic polychlorinated biphenyl (PCB) mixture Aroclor 1221, the anti-androgenic fungicide vinclozolin (VIN), or the vehicle (6% dimethylsulfoxide in sesame oil; VEH) during embryonic development. The F1 male and female offspring were bred through the paternal- or maternal-lineage with untreated partners to generate F2 offspring. This process was repeated through both maternal and paternal lineages to create the F3 generation. Maternal care of F2 dams towards their F3 offspring was altered in a lineage-dependent manner, particularly in PCB paternal-lineage animals. When F3 pups were recorded for ultrasonic vocalizations (USVs) following separation from the mother, the rate of neonatal USVs in F3 offspring were decreased in PCB paternal-lineage pups. In adulthood, anxiety-like behaviors of the F3 rats were tested, with only small effects of EDCs detected. These interactions of maternal behaviors and EDC effects across generations, especially via the paternal lineage, has implications for health and environmental responses in wildlife and humans.
•PCBs and vinclozolin are EDCs that cause developmental and transgenerational effects.•EDCs affect maternal behavior in the F2 generation, exposed as germ cells.•Ultrasonic vocalizations in the F3 pups were altered transgenerationally by EDCs.•Maternal behavior and EDC inheritance interact across generations.
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