Influence of perinatal exposure to an endocrine disruptor mixture on the renal microenvironment of aged male rat offspring: histopathological aspects

The developmental origins of health and disease hypothesis suggests that environmental exposures during critical developmental windows increase the risk of disease later in life. Among these, endocrine disruptors (EDs) are particularly concerning due to their ubiquitous presence. The kidneys are highly susceptible to EDs toxicity during the perinatal period; however, long-term effects of ED mixtures on renal structure in aging remain unclear. This study aimed to characterize the renal histoarchitecture of aged rats after perinatal exposure to an ED mixture. Pregnant Sprague-Dawley rats were assigned to two groups: Control (corn oil, 2 ml/kg) and ED Mix (32.11 mg/kg/day of 12 EDs, including phthalates, pesticides, UV filters, bisphenol A, and butylparaben, in corn oil). Exposure occurred from gestational day 7 to postnatal day 21. Offspring were euthanized at postnatal day 440. ED mixture exposure did not affect the organosomatic index. However, ED Mix offspring presented renal lesions, including necrosis and tubular fusion, with a trend toward increased pathological changes. Morphometric analysis revealed enlarged nuclei and increased nuclear perimeters in the cortex and medulla, along with altered cellular organization in glomerular and medullary regions. Collagen organization was disrupted, with increased fibrosis in cortical and medullary compartments and reduced collagen type I and III in glomeruli. These findings indicate that perinatal exposure to an ED mixture alters nuclear phenotype and promotes extracellular matrix remodeling in distinct renal compartments. Such changes suggest long-term impacts on renal structure and function, emphasizing the health risks associated with early-life exposure to complex ED mixtures.