SP22 sperm protein as a potential biomarker of fertility in humans: A preliminary study.

Infertility affects approximately 15% of couples of reproductive age, and 50% of the cases are directly related to men. The evaluation of male fertility is based on analyses of routine seminal parameters and the use of more advanced techniques can help identify fertility biomarkers. SP22 sperm protein is considered a biomarker in murine species since its concentration is highly correlated with sperm fertility. As the role of this protein as a biomarker is already well-established in other species, we hypothesized that this same correlation could apply to human. Thus, the present study aimed to investigate possible correlations between SP22 concentration and sperm parameters in fertile and infertile men. For this, a study was carried out on 21 volunteers' seminal samples who were grouped according to fertility as fertile (n = 10) or infertile (n = 11). Conventional and functional sperm analyses, membrane protein extraction, quantification and immunolocalization of SP22 were performed. The infertile volunteers showed an increase in the percentage of sperm with abnormalities in head morphology and a decrease in the percentage of sperm with intact plasma membrane and damaged acrosomal membrane. Serum concentration of the hormone SHBG was also decreased in infertile volunteers. The damage to the plasma membrane was positively correlated with the superoxide anion production. Although none of the functional parameters were correlated with SP22 concentration, type D sperm motility was negatively correlated and type A+B sperm motility was positively correlated. This preliminary study opens new paths in the characterization of SP22 as a non-invasive biomarker for predicting fertility/infertility.

Effects of isolated or combined exposure to sibutramine and rosuvastatin on reproductive parameters of adult male rats.

Many obese patients are exposed to hypolipidemic and serotonin-norepinephrine reuptake inhibitor (SNRI) drugs. Statins are one of the most marketed drugs in the world to treat dyslipidemia, while sibutramine, a SNRI drug, is prescribed in some countries to treat obesity and is detected as an additive in many adulterated weight loss supplements marketed worldwide. Previous studies reported adverse effects of isolated exposure to these drugs on male rat reproductive parameters. In the present work, we further investigated male reproductive toxicity of these drugs, administered in isolation or combination in adult rats for a longer period of treatment. Adult male rats (90 days) were treated (gavage) for 70 days with saline and dimethyl sulfoxide (control), sibutramine (10 mg/kg), rosuvastatin (5 mg/kg), or rosuvastatin combined with sibutramine. Sibutramine alone or with rosuvastatin, promoted a reduction in food intake and body weight gain, weight of the epididymis, ventral prostate and seminal vesicle; as well as decreased sperm reserves and transit time through the epididymis; androgen depletion; and increased index of cytoplasmic droplet. The rosuvastatin-treated group showed reduced frequency of ejaculation. Exposure to this drug alone or combined with sibutramine impaired epididymal morphology. Co-exposed rats had altered epididymal morphometry, and seminal vesicle and testis weights. The rats also showed decreased fertility after natural mating and a trend toward a delay in ejaculation, suggesting a small synergistic effect of these drugs. Given the greater reproductive efficiency of rodents, the results obtained in the present study raise concern regarding possible fertility impairment in men taking statins and SNRI drugs.

Interpreting histopathology in the epididymis.

While most of this Special Issue is devoted to the testis (which is where most drug and chemically induced toxicity of the male reproductive tract is identified), being able to recognize and understand the potential effects of toxicants on the epididymis is immensely important and an area that is often overlooked. The epididymis is the organ where the post-testicular sperm differentiation occurs, through a complex and still not completely understood sperm maturation process, allowing them to fertilize the oocyte. Also in the epididymis, sperm are stored until ejaculation, while being protected from immunogenic reaction by a blood-epididymis barrier. From a toxicologic perspective the epididymis is inherently complicated as its structure and function can be altered both indirectly and directly. In this review we will discuss the factors that must be considered when attempting to distinguish between indirect and direct epididymal toxicity and highlight what is currently known about mechanisms of epididymal toxicants, using the rat as a reference model. We identify 2 distinguishable signature lesions - one representing androgen deprivation (secondary to Leydig cell toxicity in the testis) and another representing a direct acting toxicant. Other commonly observed alterations will also be shown and discussed. Finally, we point out that many of the key functions of the epididymis can be altered in the absence of a detectable change in tissue structure. Collectively, we hope this will provide pathologists with increased confidence in identification of epididymal toxicity and enable more informed guidance as mechanism of action is considered.

Epididymis-specific pathologic disorders in rats exposed to gossypol from weaning through puberty.

Previous work in our laboratory revealed that the pubertal period of reproductive development in the male rat was particularly vulnerable to gossypol exposure, with a higher frequency of round structures in the lumen of the cauda epididymidis in the treated rats. Herein, we utilized hemicastration and electron microscopy to confirm that the epididymis is a definitive target of gossypol. Although exposure to gossypol from weaning through puberty caused a significant decrease in daily sperm production, as well as in the concentration of sperm in the epididymis, serum testosterone levels and reproductive organ weights were not altered. In gossypol treated rats, sperm morphology was compromised severely, but the epithelium in testis and epididymis appeared morphologically normal. Ultrastructural examination revealed that round structures, present only in gossypol exposed males, represented: (1) principal cells exfoliated from the epididymal epithelium; (2) epididymal epithelial cell cytoplasm containing degenerating sperm; and (3) degenerating epithelial cells, consisting of vesicles and particles of different sizes, forms and densities. Taken together, the data confirm that gossypol targets the epididymis, disturbing both the structure and function of this organ, and presumably disrupts sperm maturation.