Aging is associated with a drastic decline in fertility/fecundity and with an increased risk of pregnancy complications. Resveratrol (RES), a natural polyphenolic compound, has shown anti-oxidant and anti-inflammatory activities in both human and animal models, thus representing a potential therapeutic and prophylactic anti-aging supplement. Here, we investigated whether preconceptional resveratrol supplementation improved reproductive outcomes in mid-aged (8-month-old) and old (12-month-old) C57BL/6J female mice. Female siblings were cohoused and assigned to either RES or vehicle supplementation to drinking water for 10 consecutive weeks. Subsequently, females were mated with non-supplemented males and their pregnancy outcomes were monitored. RES improved mating success in old, but not in mid-aged females, and prevented the occurrence of delivery complications in the latter. These results indicate that preconceptional RES supplementation could partially improve age-related reproductive complications, but it was not sufficient to restore fecundity in female mice at a very advanced age.

Neurodevelopmental disorders arise from the interplay between genetic and maternal influences during prenatal life. Using the BTBR T⁺Itpr3^tf/J (BTBR) mouse model of idiopathic autism and the C57BL/6J (B6) control strain, we examined how embryonic genotype and maternal environment interact to shape placental development, fetal growth, and postnatal behavior. Quantitative analyses of fetal and placental weights confirmed strain- and stage-specific growth restriction in BTBR conceptuses (n = 18-35 conceptuses from 3 litters per strain). Morphological assessment further demonstrated a substantial strain effect on placental layers, characterized by enlarged labyrinth compartments and reduced glycogen stores in BTBR placentas. Through reciprocal embryo transfers (n = 3 litters per strain combination), we found that maternal strain predominantly determined placental morphology: BTBR and B6 conceptuses developed placentas that mirrored the histological architecture of their foster mothers. In contrast, autism-like behaviors remained specific to BTBR offspring, regardless of the maternal strain, indicating a prevalent embryonic genotype effect on behavioral outcomes. Placental transcriptomic profiling (n = 4 conceptuses per strain) revealed an enrichment in lipid metabolism, nutrient transport, and extracellular matrix remodeling pathways. Together, these findings indicate that maternal factors primarily shape placental architecture, whereas embryonic determinants are linked with the development of autism-like behaviors in the BTBR mouse model. These insights advance our understanding of early-life determinants of autism and suggest placental metabolism as a potential target for early diagnosis of neurodevelopmental risk.

The European wisent (Bison bonasus), an iconic yet genetically vulnerable species, faces ongoing conservation challenges due to a restricted gene pool. Advances in induced pluripotent stem cell (iPSC) technology offer promising prospects for preserving and restoring genetic diversity in endangered species. In this study, we sought to reprogram wisent somatic cells into iPSCs using the PiggyBac transposon system, a non-viral method known for being successfully applied in bovine species. We applied a six-factor reprogramming cocktail (OCT4, SOX2, KLF4, LIN28, c-MYC, NANOG) alongside small-molecule enhancers to fibroblasts isolated from adult wisent tissue. While initial colony formation was observed, the reprogrammed cells exhibited limited proliferation and failed to maintain stable pluripotency, suggesting intrinsic barriers to complete reprogramming. Despite optimizing culture conditions, including hypoxia and extracellular matrix modifications, the reprogramming efficiency remained low. Our findings indicate that wisent somatic cells may require alternative reprogramming strategies, such as new-generation delivery systems and epigenetic modulators, to achieve stable iPSC lines. This study underscores the need for species-specific optimization of reprogramming protocols and highlights the potential of emerging cellular technologies for conservation efforts. Future research integrating advanced reprogramming tools may pave the way for genetic rescue strategies in wisent and other endangered species.

Lipid droplets (LDs) are multifunctional organelles that serve as reservoirs of fatty acids, and act as substrates for β-oxidation and ATP synthesis during mammalian preimplantation development. However, the genetic and lineage-specific regulation of their biogenesis and utilization remains poorly understood. Here, we report a mouse model of embryonic LD deficiency, the BTBR T+ Itpr3tf/J inbred strain, characterized by the absence of oocyte-inherited LD clusters in zygotes and a rapid depletion of de novo generated LDs at the morula-to-blastocyst transition stage, as compared to C57BL/6J controls. Lineage-resolved analyses revealed a selective depletion of large LDs in the trophectoderm while lipids were consistently accumulated in the inner cell mass, indicating lineage-specific lipid utilization. Pharmacological inhibition of autophagy or cytoplasmic lipase activity caused LD accumulation and developmental arrest specifically in BTBR, indicating an essential dependence on lipid mobilization. Modulation of mitochondrial fatty acid β-oxidation by etomoxir inhibition and L-carnitine stimulation shifted lipid droplet enlargement and allocation between lineages in a strain-specific manner, and altered epiblast cell numbers, linking lipid catabolism to lineage fitness. These findings identify a genetically encoded, lineage-specific LD program linking lipid mobilization to blastocyst morphogenesis, embryonic survival, and lineage homeostasis.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition with diverse genetic and environmental origins. Rodent models, particularly mice, have proven invaluable in studying the underlying mechanisms of ASD, offering insights into the genetic mutations and neurobiological processes that may contribute to the disorder in the human population. This review examines key rodent models to study genetic and environmental factors affecting the etiology and pathogenesis of ASD. While these models successfully mimic many core ASD symptoms, they face limitations in fully replicating the social and cognitive complexities of human ASD. Future research should prioritize improving models of gene-environment interactions and exploring humanized approaches to bridge the gap between animal studies and clinical applications. These efforts are essential for advancing our understanding of ASD and developing effective therapeutic strategies.