The aim of this review study is to elucidate the effects that phosphodiesterase 5 (PDE5) inhibitors exert on spermatozoa motility, capacitation process and on their ability to fertilize the oocyte. Second messenger systems such as the cAMP/adenylate cyclase (AC) system and the cGMP/guanylate cyclase (GC) system appear to regulate sperm functions. Increased levels of intracytosolic cAMP result in an enhancement of sperm motility and viability. The stimulation of GC by low doses of nitric oxide (NO) leads to an improvement or maintenance of sperm motility, whereas higher concentrations have an adverse effect on sperm parameters. Several in vivo and in vitro studies have been carried out in order to examine whether PDE5 inhibitors affect positively or negatively sperm parameters and sperm fertilizing capacity. The results of these studies are controversial. Some of these studies demonstrate no significant effects of PDE5 inhibitors on the motility, viability, and morphology of spermatozoa collected from men that have been treated with PDE5 inhibitors. On the other hand, several studies demonstrate a positive effect of PDE5 inhibitors on sperm motility both in vivo and in vitro. In vitro studies of sildenafil citrate demonstrate a stimulatory effect on sperm motility with an increase in intracellular cAMP suggesting an inhibitory action of sildenafil citrate on a PDE isoform other than the PDE5. On the other hand, tadalafil's actions appear to be associated with the inhibitory effect of this compound on PDE11. In vivo studies in men treated with vardenafil in a daily basis demonstrated a significantly larger total number of spermatozoa per ejaculate, quantitative sperm motility, and qualitative sperm motility; it has been suggested that vardenafil administration enhances the secretory function of the prostate and subsequently increases the qualitative and quantitative motility of spermatozoa. The effect that PDE5 inhibitors exert on sperm parameters may lead to the improvement of the outcome of assisted reproductive technology (ART) programs. In the future PDE5 inhibitors might serve as adjunct therapeutical agents for the alleviation of male infertility.
Pregnancies achieved by assisted reproduction technologies, particularly by intracytoplasmic sperm injection (ICSI) procedures, are susceptible to genetic risks inherent to the male population treated with ICSI and additional risks inherent to this innovative procedure. The documented, as well as the theoretical, risks are discussed in the present review study. These risks mainly represent that consequences of the genetic abnormalities underlying male subfertility (or infertility) and might become stimulators for the development of novel approaches and applications in the treatment of infertility. In addition, risks with a polygenic background appearing at birth as congenital anomalies and other theoretical or stochastic risks are discussed. Recent data suggest that assisted reproductive technology might also affect epigenetic characteristics of the male gamete, the female gamete, or might have an impact on early embryogenesis. It might be also associated with an increased risk for genomic imprinting abnormalities.
Pregnancies achieved by assisted reproduction technologies and particularly by ooplasmic injections of either in vivo or in vitro generated immature male germ cells are susceptible to genetic risks inherent to the male population treated with assisted reproduction and additional risks inherent to these innovative procedures. The documented, as well as the theoretical risks, are discussed in this review. These risks represent mainly the consequences of genetic abnormalities underlying male infertility and may become stimulators for the development of novel approaches and applications in the treatment of infertility. Recent data suggest that techniques employed for in vitro spermatogenesis, male somatic cell haploidization, stem cell differentiation in vitro and assisted reproductive technology may also affect the epigenetic characteristics of the male gamete, the female gamete, or may have an impact on early embryogenesis. They may be also associated with an increased risk for genomic imprinting abnormalities. Production of haploid male gametes in vitro may not allow the male gamete to undergo all the genetic and epigenetic alterations that the male gamete normally undergoes during in vivo spermatogenesis.
We evaluated the potential for growth and intrauterine development of embryos generated from the fertilization of oocytes with spermatozoa recovered from animals with chronic renal failure (CRF). Group A included sham-operated rats (n = 28), group B1 involved CRF rats that had undergone erythropoietin plus bromocryptine treatment (n = 28), and group B2 included CRF rats that had received normal saline. Embryos derived from the in vitro fertilization of oocytes with spermatozoa recovered from rats of group A or group B1 or group B2 were transferred to female recipients. We induced CRF in a group of rats (group B; n = 56; the total kidney volume was reduced to one-sixth with two operations). One week after the second operation, the rats of group B were randomly divided into group B1 (they subsequently received bromocryptine plus erythropoietin) and group B2 (they received injections of saline). Nine weeks after the second operation, the fertility of each male rat was assessed by mating tests and in vitro fertilization of oocytes. The mean litter size was significantly smaller in the subpopulation of fertile animals in group B2 than in the fertile rats of group B1 and in the fertile rats of group B1 than in the fertile rats of group A. Per cent of transferred blastocysts that developed into alive offspring were significantly lower in group B2 than in group B1 and in group B1 than in group A. Epididymal spermatozoa demonstrated a significantly larger DNA-oxidative damage in group B2 than in group B1 and in group B1 than in group A. These findings demonstrate that sperm-DNA damage because of CRF development is accompanied by a defect in the development of embryos generated in vitro. We may suggest that bromocryptine and erythropoietin protecting sperm DNA from oxidative damage improve reproductive potential in rats with CRF.
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