Protective effect of lipoic acid on reproductive toxicity induced by pentadecafluorooctanoic acid in male rats

Background The reproductive damage induced by pentadecafluorooctanoic acid (PFOA) has raised increasing concerns, but if lipoic acid (LA) alleviates the damage is unknown.

Objective This experiment investigates whether LA could protect against the reproductive toxicity of PFOA in male rats.

Methods Forty male SD rats aged six weeks were randomly divided into five groups (eight rats in each group):blank control group (corn oil), LA control group (100 mg·kg^-1 LA), PFOA exposure group (10 mg·kg^-1 PFOA), low-dose LA intervention group (10 mg·kg^-1 PFOA+50 mg·kg^-1 LA), and high-dose LA intervention group (10 mg·kg^-1 PFOA+100 mg·kg^-1 LA). After seven weeks of administration by gavage, blood samples were collected from abdominal aorta, testes and epididymis were harvested, and viscera coefficients were calculated. The sperm count was measured using computer aided sperm analysis system. Pathological observation of testicular tissues was conducted after HE staining. The activities of succinic acid dehydrogenase (SDH) and lactate dehydrogenase (LDH) in testis were detected by spectrophotometry, the contents of testosterone (T) and follicle-stimulating hormone (FSH) in serum by enzyme-linked immunosorbent assay (ELISA), and the protein expression level of follicle-stimulating hormone receptor (FSHR) in rat testis by Western blotting.

Results The testicular organ coefficient of the PFOA exposure group was higher than those of the blank control group and the LA control group(9.41±0.40)‰, (7.50±0.66)‰, (8.21±0.94)‰; P < 0.05, and the epididymal sperm count was lower(10.63±2.07)×10⁶, (21.00±3.89)×10⁶, (17.63±5.01)×10⁶; P < 0.05. The results of testicular histopathology showed reduced layers of disordered spermatogenic cells in the rat spermatogenic tubule of the PFOA exposure group compared with the blank control group, along with more vacuolization changes in the spermatogenic epithelium and less and disarranged leydig cells; while these lesions in the LA intervention groups were significantly reduced. The activities of SDH and LDH decreased after the PFOA treatment compared with the blank control group(1.15±0.44), (1.74±0.58) U·g^-1; (1.82±0.64), (2.58±0.64) U·g^-1; P < 0.05, but the activity of SDH reversed after the 100 mg·kg^-1 LA intervention (P < 0.05). In addition, compared with the blank control group, the rats in the PFOA exposure group had lower T levels, higher FSH levels, and lower FSHR protein expression levels in the testicular tissues (P < 0.05), and the rats after LA intervention showed lower FSH levels (far bigger falls for the high-dose LA intervention group) and alleviated reduction of FSHR protein expression levels.

Conclusion PFOA has a reproductive toxicity effect on male rats, while appropriate LA supplementation can protect against the reproductive injury caused by PFOA.