AI Article Synopsis
- PFDoA (Perfluorododecanoic acid) is an endocrine disruptor found in contaminated food and water, and its effects on Leydig cell regeneration from stem Leydig cells are not well understood.
- In a study with adult male rats, PFDoA exposure led to reduced serum testosterone and hormone levels, decreased Leydig cell numbers, and inhibited proliferation at higher doses after Leydig cell elimination.
- PFDoA also down-regulated the expression of specific genes and proteins related to Leydig and Sertoli cells, suggesting that short-term exposure impairs Leydig cell regeneration through multiple mechanisms.
Article Abstract
Perfluorododecanoic acid (PFDoA) is an endocrine-damaging compound in contaminated food and water. However, the potential role and underlying mechanism of PFDoA in Leydig cell regeneration from stem Leydig cells remain unclear. The current study aims to investigate the effect of PFDoA on the regeneration of Leydig cells in the testis of rats treated with ethylene dimethane sulfonate (EDS). PFDoA (0, 5 or 10Â mg/kg/day) was gavaged to adult Sprague-Dawley male rats for 8 days, and 75Â mg/kg EDS was intraperitoneally injected to eliminate Leydig cells to initiate its regeneration from day 21-56 after EDS. The serum testosterone levels in the 5 and 10Â mg/kg/day PFDoA groups were significantly reduced at day 21 after EDS and the levels of serum luteinizing hormone and follicle-stimulating hormone were significantly decreased in the 10Â mg/kg/day PFDoA groups at day 56 after EDS. PFDoA significantly reduced Leydig cell number and proliferation at a dose of 10Â mg/kg at days 21 and 56 after EDS. PFDoA significantly down-regulated the expression of Leydig cell-specific genes (Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1 and Cyp17a1) and their proteins at both doses at days 21 and 56 after EDS. PFDoA significantly down-regulated the gene expression of Sertoli cells (Fshr, Dhh, and Sox9) at 5Â mg/kg or higher at days 21 and 56 after EDS. In addition, we found that PFDoA significantly inhibited EdU incorporation into putative stem Leydig cells and their differentiation into the Leydig cell lineage in vitro. In conclusion, short-term PFDoA exposure in adulthood delayed the regeneration of Leydig cells by preventing Leydig cells from stem cells via multiple mechanisms.
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| http://dx.doi.org/10.1016/j.fct.2021.112152 | DOI Listing |
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