Impact of PCB and p,p'-DDE contaminants on human sperm Y : X chromosome ratio: Studies in three European populations and the inuit population in Greenland

Recent studies indicate that persistent organohalogen pollutants (POPs) may contribute to sex ratio changes in offspring of exposed populations. Our aim in the present study was to investigate whether exposure to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and dichlorodiphenyldichloroethene (pp'-DDE) affects sperm Y:X chromosome distribution. SUBJECTS AND METHODS: We obtained semen and blood for analysis of PCB-153 and pp'-DDE levels from 547 men from Sweden, Greenland, Poland (Warsaw), and Ukraine (Kharkiv), with regionally different levels of POP exposure. The proportion of Y- and X-chromosome-bearing sperm in the semen samples was determined by two-color fluorescence in situ hybridization analysis. RESULTS: Swedish and Greenlandic men had on average significantly higher proportions of Y sperm (in both cohorts, 51.2%) and correspondingly higher lipid-adjusted concentrations of PCB-153 (260 ng/g and 350 ng/g, respectively) compared with men from Warsaw (50.3% and 22 ng/g) and Kharkiv (50.7% and 54 ng/g). In the Swedish cohort, log-transformed PCB- 153 and log-transformed pp'-DDE variables were significantly positively associated with Y-chromosome fractions (p-values 0.04 and < 0.001, respectively). On the contrary, in the Polish cohort PCB-153 correlated negatively with the proportion of Y-bearing fraction of spermatozoa (p = 0.008). CONCLUSIONS: The present study indicates that POP exposure might be involved in changing the proportion of ejaculated Y-bearing spermatozoa in human populations. Intercountry differences, with different exposure situations and doses, may contribute to varying Y:X chromosome ratios

Androgen receptor CAG repeat length correlates with semen PSA levels in adolescence.

BACKGROUND: Androgens exert their action through the androgen receptor (AR). The length of the AR CAG repeat is inversely correlated to receptor function and short CAG length might be a risk factor for development of prostate cancer. Our aim was to investigate whether CAG repeat number might have an impact on prostate function in adolescence. METHODS: AR genotyping was performed by direct sequencing of leukocyte DNA from 274 military conscripts. All men underwent endocrine evaluation and semen analysis. RESULTS: PSA in seminal plasma, total sperm count and motility all are inversely correlated with CAG numbers (rho = -0.128, P = 0.038; rho = -0.156, P = 0.010; rho = -0.158, P = 0.011), whereas serum levels of free testosterone (rho = 0.132; P = 0.029) and luteinizing hormone (rho = 0.126; P = 0.037) are positively correlated to CAG length. No correlation between seminal PSA and serum testosterone, neither free nor total, was found. CONCLUSIONS: In adolescence, AR genotype, but not serum testosterone, is associated with the level of seminal PSA

Androgen receptor gene CAG repeat length as a modifier of the association between persistent organohalogen pollutant exposure markers and semen characteristics

Objectives Exposure to persistent organohalogen pollutants was suggested to impair male reproductive function. A gene-environment interaction has been proposed. No genes modifying the effect of persistent organohalogen pollutants on reproductive organs have yet been identified. We aimed to investigate whether the CAG and GGN polymorphisms in the androgen receptor gene modify the effect of persistent organohalogen pollutant exposure on human sperm characteristics. Methods Semen and blood from 680 men [mean (SD) age 34 (10) years] from Greenland, Sweden, Warsaw (Poland) and Kharkiv (Ukraine) were collected. Persistent organohalogen pollutant exposure was assessed by measuring serum levels of 2,2,4,4,5,5'-hexachlorobiphenyl (CB-153) and dichlorodiphenyl dichloroethene (p,p'-DDE). Semen characteristics (volume, sperm concentration, total count proportion of progressively motile and morphology) and DNA fragmentation index (DFI) were determined. CAG and GGN repeat lengths were determined by direct sequencing of leukocyte DNA. Results A statistically significant interaction was found between the CB-153 group and CAG repeat category in relation to sperm concentration and total sperm count (P=0.03 and 0.01, respectively). For p,p'-DDE, in the European cohorts a significant interaction was found in relation to DFI (P=0.01). For CAG<20, sperm concentration and total sperm count were 35 and 42% lower, respectively, when the group with CB-153 exposure above median was compared with that below the median. DF1 was 40% higher in the high p,p'-DDE exposure group for CAG < 21. Conclusions This study indicated that the androgen receptor CAG repeat length might modify the susceptibility of an individual to the adverse effects of persistent organohalogen pollutant exposure on semen quality. Other studies regarding this matter are warranted