Lead Toxicity and The Hypothalamic-Pituitary-Testicular Axis

Abstract

Environmental exposure to toxic levels of lead (Pb) occurs in a number of industries with potential adverse effects on the reproductive capacity of exposed men. Clinical and animal studies indicate that abnormalities of spermatogenesis result from toxic lead exposure, but eventual histopathologic alterations involved have not been identified. To explore putative abnormalities in the reproductive gonadotropic axis following lead intoxication, experimental animals when exposed to low levels of lead, 65 days old animals were treated with distilled water containing 0,0 mg (control), 10 mg lead (Pb)/Kg/day and 15 mg lead (Pb)/Kg/day intraperitoneally for 20 days. At the end of treatment, the animals were sacrificed and the blood collected for luteinizing hormone (LH) and testosterone assays. The testis was processed for histological analysis. The results showed a high serum concentration of LH and testosterone in lead-treated animals compared to controls. Histological examination of testis showed deformities in testicular morphology of lead intoxicated animals with gross damage within the somniferous tubules. A strong correlation was established between LH and testosterone suggesting an alteration in the endocrine components of the gonadotropic axis. Histological examination of pituitary gland showed some degenerative changes in endocrine cells of lead group. Changes in LH and testosterone levels suggest that Pb exposure during the critical time of sexual differentiation induces reproductive axis abnormalities in adulthood. In conclusion, lead has a gonadotoxic effect by decreasing LH and testosterone levels and damaging the testis seminiferous tubules. Catalase activity was significantly reduced in the lead group following 65 days of exposure which possibly indicates that lead might had other mechanisms of action, such as increasing oxidative damage.

Impaired hypothalamic-pituitary-testicular axis activity, spermatogenesis, and sperm function promote infertility in males with lead poisoning

“…At the testicular level, lead impairs testicular LH receptor concentrations and steroidogenesis at the pubertal stage (Ronis et al , 1996). Another animal study with lead exposure during sexual development showed degenerative changes in gonadotropic cells of the pituitary gland, thus accounting for suppressed plasma LH and testosterone levels into adulthood (Ait Hamadouche et al , 2013).…”

“…ROS halts synthesis of sulfhydryl antioxidants and prevents enzymatic reactions (Vigeh et al , 2011). In fact, lead itself has high affinity to sulfhydryl residues in proteins, thus acting as a nonspecific enzyme inhibitor and arresting their antioxidant activity (Ait Hamadouche et al , 2013). As oxidative stress disturbs chromatin condensation, it has been suggested that the under-protamination of sperm DNA could automatically lead to DNA fragmentation (Henkel et al , 2010).…”

“…Brain catalase activity was found to be significantly decreased in a rat study looking at lead-induced HPT dysfunction; this will ultimately permit oxidative damage in cells (Ait Hamadouche et al , 2013). Increased IL-7, IL-10, IL-12, and TNF-α cytokine levels have been found to accompany lead-related oxidative stress, particularly in semen (Kasperczyk et al , 2015).…”

Endocrine disrupting metals lead to alteration in the gonadal hormone levels in Nigerian e-waste workers

“…EST is also essential for spermiogenesis. (13) The strong negativity observed in the correlation of TESTO and EST with toxic metals shows the effect of the toxic metals on the endocrine functions of the e-waste workers. The workers are therefore at risk of developing pathological conditions that are associated with reproductive endocrine dysfunction, the effect of which may cumulatively lead to sterility and cancer.…”

“…Derivatives of the amino acid tyrosine, are secreted by the thyroid (thyroxine and triiodothyronine) and the adrenal medullae (epinephrine and norepinephrine. (12,13) Previous studies have shown changes in the concentration of hormones in workers occupationally exposed to heavy metals such as lead (Pb). These changes were proposed to be mediated at the hypothalamic-pituitary level.…”