Low-level exposure to environmental lithium element affects male reproductive outcomes: Results from the MARHCS cohort study in Chongqing, China and in vivo animal experiments

This study examined the effects of lithium exposure at environmental levels on semen quality and sex hormone levels. Questionnaires and biological samples were collected from 582 college students recruited in Chongqing, China. Sex hormones and semen parameters were measured by ELISA and CASA, respectively. Sperm telomere length and mitochondrial DNA copy number were determined using real-time Q-PCR. Lithium levels were quantified by ICP-MS. In addition, C57BL/6 mice were administered lithium chloride at doses within the range of environmental levels (LiCl; 0, 4.3, 12.8, and 38.4 mg/kg) for 35 days, and the expression of key proteins involved in testosterone synthesis was detected by western blot assay. In the population study, the median lithium levels in urine and seminal plasma were 18.80 and 5.38 μg/L, respectively. Each interquartile range increase of lithium levels in both urine and seminal plasma were associated with decreased serum testosterone (−2.47 %, 95 % CI: −4.52 %, −0.38 % for urine; −2.67 %, 95 % CI: −4.79 %, −0.50 % for seminal plasma) and progesterone (−6.38 %, 95 % CI: −11.09 %, −1.42 % for urine; −8.78 %, 95 % CI: −13.20 %, −4.04 % for seminal plasma). Mice treated with the highest LiCl dose (38.4 mg/kg) had significantly lower sperm motility, sperm concentration, and testosterone, progesterone, estradiol, and prolactin levels than mice in the control group (all p < 0.05), and their Leydig cells showed marked mitochondrial vacuolation and swelling. These results support that environmental lithium exposure leads to decreased semen quality and testosterone by impairing Leydig cells.