Semen from 10 932 male partners of infertile couples was analysed and sperm parameter trends were evaluated at the Reproduction Biology Laboratory of the University Hospital of Marseille (France) between 1988 and 2007. After 3-6 days of abstinence, semen samples were collected. Measurements of seminal fluid volume, pH, sperm concentration, total sperm count, motility and detailed morphology of spermatozoa were performed. Sperm parameters were analysed on the entire population and in men with normal total numeration (o40 million per ejaculate). The whole population demonstrated declining trends in sperm concentration (1.5% per year), total sperm count (1.6% per year), total motility (0.4% per year), rapid motility (5.5% per year) and normal morphology (2.2% per year). In the group of selected samples with total normal sperm count, the same trends of sperm quality deterioration with time were observed. Our results clearly indicate that the quality of semen decreased in this population over the study period. Keywords: environment; male infertility; regional differences; semen quality; sperm parameters INTRODUCTION Numerous studies suggest a decline in semen quality in some parts of the world. 1-8 By contrast, other studies have shown no evidence of deteriorating semen quality. 9-16 Some studies concern infertile couples, while others analyse normal sperm parameters. Thus, a worldwide decreasing trend in semen parameter values can be neither confirmed nor rejected. 17 It was recently reported that fecundity is affected by this decrease. 18,19 It was speculated that decreasing sperm parameters are in response to adverse environmental factors. Nevertheless, the observed discrepancies between studies suggest regional differences in semen quality. [20][21][22] Variations in environmental factors, industrial pollution and/or lifestyle could explain these discrepancies. A large number of environmental factors can pollute air, drinking water and food. This can directly alter the male gonad by blood-testis barrier disruption and cellular toxicity, or disrupt androgen biosynthesis and action. Among these environmental factors, oestrogenic or anti-androgenic endocrine disrupting compounds inhibit critical cellular process controlling steroidogenesis in Leydig cells and androgen binding to the androgen receptor. 23 It has been hypothesized that endocrine disrupting compounds play a major role in the aetiology of increased incidence of testicular dysgenesis syndrome which gathers decreased quality of semen, cryptorchidism, hypospadias and testicular cancer. 24 Chemicals with hormone-like activity can also

Our results indicate that the post-meiotic spermatogenesis in 13-1217 is not a consequence of mosaicism or retention of a key AZFb gene. On the contrary, since the Hg-L Y chromosome carried by 13-1217 is uncommon in Western Europe, a Y-linked modifier locus remains a possible explanation for the oligozoospermia observed in patient 13-1217. Further cases must now be studied to understand how germ cells complete spermatogenesis in the absence of the AZFb interval.

Pachytene analysis was undertaken in a male patient heterozygous for a 14q22q Robertsonian translocation. The relatively low rate of XY autosome association led us to examine the relationships existing between the chromosomes involved in the translocation, the rate of XY-autosome association and the degree of spermatogenic failure. Cytogenetic investigations in infertile men and the results of the meiotic studies suggest a direct correlation between the frequency of XY-autosome association at pachytene and the degree of spermatogenic failure. Whether associations arise as a consequence or cause of germ cell failure is still not certain.

In industrial countries, evidence suggests that semen quality has been steadily decreasing over the past 5 decades. We employed a short questionnaire to examine the association between self-reported physical or chemical occupational exposures and semen quality. The study included 402 men consulting for couple infertility (314 with oligospermia, asthenospermia, or teratospermia and 88 with normal semen; World Health Organization criteria). Exposure effects on global sperm quality and total sperm count, sperm motility, and sperm morphology were investigated. We found significant associations between semen impairment and occupational risk factors such as exposure to heavy metals (adjusted odds ratio [OR] = 5.4; 95% confidence interval [CI], 1.6-18.1), solvents (OR = 2.5; 95% CI, 1.4-4.4), fumes (OR = 1.9; 95% CI, 1.1-3.4), and polycyclic aromatic hydrocarbons (OR = 1.9; 95% CI, 1.1-3.5). Exposure to pesticides or cement was nearly significant (OR = 3.6; 95% CI, 0.8-15.8, and OR = 2.5; 95% CI, 0.95-6.5, respectively). Physical risk factors were associated with some sperm anomalies, such as mechanical vibrations with oligospermia and teratospermia as well as excess heat and extended sitting periods with impaired motility. Exposure to ionizing radiation and electromagnetic fields was not associated with semen impairment; these results, however, may be skewed, because very few subjects reported such exposure. Despite the small dataset, self-reported exposures were correlated with semen impairment. This approach may be recommended in routine clinical practice to seek relationships between occupational exposures to reprotoxic agents and impaired semen parameters. This knowledge would allow preventive measures in the workplace to be established and could be complemented by the use of biomarkers to better characterize exposure to chemical substances and their spermiotoxic effects.

BackgroundBisphenol A (BPA) is one of the most widespread chemicals in the world and is suspected of being responsible for male reproductive impairments. Nevertheless, its molecular mode of action on spermatogenesis is unclear. This work combines physiology and toxicogenomics to identify mechanisms by which BPA affects the timing of meiosis and induces germ-cell abnormalities.MethodsWe used a rat seminiferous tubule culture model mimicking the in vivo adult rat situation. BPA (1 nM and 10 nM) was added to the culture medium. Transcriptomic and meiotic studies were performed on the same cultures at the same exposure times (days 8, 14, and 21). Transcriptomics was performed using pangenomic rat microarrays. Immunocytochemistry was conducted with an anti-SCP3 antibody.ResultsThe gene expression analysis showed that the total number of differentially expressed transcripts was time but not dose dependent. We focused on 120 genes directly involved in the first meiotic prophase, sustaining immunocytochemistry. Sixty-two genes were directly involved in pairing and recombination, some of them with high fold changes. Immunocytochemistry indicated alteration of meiotic progression in the presence of BPA, with increased leptotene and decreased diplotene spermatocyte percentages and partial meiotic arrest at the pachytene checkpoint. Morphological abnormalities were observed at all stages of the meiotic prophase. The prevalent abnormalities were total asynapsis and apoptosis. Transcriptomic analysis sustained immunocytological observations.ConclusionWe showed that low doses of BPA alter numerous genes expression, especially those involved in the reproductive system, and severely impair crucial events of the meiotic prophase leading to partial arrest of meiosis in rat seminiferous tubule cultures.