Consequences of Exposure to Hypobaric Hypoxia Associated with High Altitude on Spermatogenesis and Seminal Parameters: A Literature Review.

Preclinical research has provided compelling evidence indicating that exposure to hypobaric hypoxia (HH) results in a deterioration of spermatogenesis. This adverse effect extends to the underlying molecular mechanisms, progressively leading to impairments in the seminiferous epithelium and germ cells and alterations in semen parameters. Indeed, several studies have demonstrated that animals exposed to HH, whether in natural high-altitude environments or under simulated hypoxic conditions, exhibit damage to the self-renewal and differentiation of spermatogenesis, an increase in germline cell apoptosis, and structural alterations in the seminiferous tubules.

Protein Kinase A (PRKA) Activity Is Regulated by the Proteasome at the Onset of Human Sperm Capacitation.

The proteasome increases its activity at the onset of sperm capacitation due to the action of the SACY/PRKACA pathway; this increase is required for capacitation to progress. PRKA activity also increases and remains high during capacitation. However, intracellular levels of cAMP decrease in this process.

Mating induces early transcriptional response in the rat endosalpinx: the role of TNF and RA.

During mating, males provide not only the spermatozoa to fertilize the oocyte but also other stimuli that are essential for initiating and maintaining the reproductive programme in females. In the mammalian oviduct, mating regulates sperm storage, egg transport, fertilization, early embryonic development, and oestradiol metabolism. However, the main molecules underlying these processes are poorly understood.

[Radionuclide synoviorthesis in hemophilia: experience in 107 patients].

Background: In patients with hemophilia, radionuclide synoviorthesis, or the intra-articular injection of a radionuclide to decrease the synovial hypertrophy tissue, aims to decrease or avoid hemarthrosis.

Aim: To evaluate the effectiveness of radionuclide synoviorthesis in hemophilia.

Material And Methods: Observational retrospective study of the evolution of 107 male patients aged 3 to 54 years who were subjected to radionuclide synoviorthesis between 2007 and 2015.

The activation of the chymotrypsin-like activity of the proteasome is regulated by soluble adenyl cyclase/cAMP/protein kinase A pathway and required for human sperm capacitation.

One of the first events of mammalian sperm capacitation is the activation of the soluble adenyl cyclase/cAMP/protein kinase A (SACY/cAMP/PKA) pathway. Here, we evaluated whether the increase in PKA activity at the onset of human sperm capacitation is responsible for the activation of the sperm proteasome and whether this activation is required for capacitation progress. Viable human sperm were incubated with inhibitors of the SACY/cAMP/PKA pathway.

Re-Epithelialization Appraisal of Skin Wound in a Porcine Model Using a Salmon-Gelatin Based Biomaterial as Wound Dressing.

The design of new functional materials for skin tissue engineering is an area of constant research. In this work, a novel wound-dressing biomaterial with a porous structure, previously formulated using salmon-gelatin as main component (called salmon-gelatin biomaterial (SGB)), was tested in vivo using pigs as skin wound models. Four weeks after cutaneous excision and implantation in the animals, the healing process did not show apparent symptoms of inflammation or infection.

Fibronectin modulates the endocannabinoid system through the cAMP/PKA pathway during human sperm capacitation.

Fibronectin (Fn) enhances human sperm capacitation via the cAMP/PKA pathway, and the endocannabinoid system participates in this process. Moreover, Fn has been linked to endocannabinoid system components in different cellular models, even though no evidence of such interactions in human sperm is available. Normal semen samples were evaluated over a 4-year period.

Design of a hybrid biomaterial for tissue engineering: Biopolymer-scaffold integrated with an autologous hydrogel carrying mesenchymal stem-cells.

Biologically active biomaterials as biopolymers and hydrogels have been used in medical applications providing favorable results in tissue engineering. In this research, a wound dressing device was designed by integration of an autologous clot hydrogel carrying mesenchymal stem-cells onto a biopolymeric scaffold. This hybrid biomaterial was tested in-vitro and in-vivo, and used in a human clinical case.

Regulation of Sperm Capacitation by the 26S Proteasome: An Emerging New Paradigm in Spermatology.

The ubiquitin proteasome system (UPS) participates in many biological processes ranging from cell cycle and antigen processing to cellular defense and signaling. Work of the last decade has made it evident that the UPS is involved in many sperm-related processes leading up to and as part of fertilization. The current knowledge of UPS involvement and changes during sperm capacitation are reviewed together with a list of known proteasome-associated sperm proteins and a discussion of the relationships between these proteins and the proteasome.

Protein phosphatases decrease their activity during capacitation: a new requirement for this event.

There are few reports on the role of protein phosphatases during capacitation. Here, we report on the role of PP2B, PP1, and PP2A during human sperm capacitation. Motile sperm were resuspended in non-capacitating medium (NCM, Tyrode's medium, albumin- and bicarbonate-free) or in reconstituted medium (RCM, NCM plus 2.

Aromatic glycosyl disulfide derivatives: evaluation of their inhibitory activities against Trypanosoma cruzi.

Aromatic oligovalent glycosyl disulfides and some diglycosyl disulfides were tested against three different Trypanosoma cruzi strains. Di-(β-D-galactopyranosyl-dithiomethylene) benzenes 2b and 4b proved to be the most active derivatives against all three strains of cell culture-derived trypomastigotes with IC50 values ranging from 4 to 11 μM at 37 °C. The inhibitory activities were maintained, although somewhat lowered, at a temperature of 4 °C as well.

A protein phosphatase 1 gamma (PP1γ) of the human protozoan parasite Trichomonas vaginalis is involved in proliferation and cell attachment to the host cell.

In this work, evidence for a critical role of Trichomonas vaginalis protein phosphatase 1 gamma (TvPP1γ) in proliferation and attachment of the parasite to the mammalian cell is provided. Firstly, proliferation and attachment of T. vaginalis parasites to HeLa cells was blocked by calyculin A (CA), a potent PP1 inhibitor.

Kinases, phosphatases and proteases during sperm capacitation.

Fertilization is the process by which male and female haploid gametes (sperm and egg) unite to produce a genetically distinct individual. In mammals, fertilization involves a number of sequential steps, including sperm migration through the female genital tract, sperm penetration through the cumulus mass, sperm adhesion and binding to the zona pellucida, acrosome exocytosis, sperm penetration through the zona and fusion of the sperm and egg plasma membranes. However, freshly ejaculated sperm are not capable of fertilizing an oocyte.

N,N'-Dithiobisphthalimide, a disulfide aromatic compound, is a potent spermicide agent in humans.

Several studies have shown that users of vaginal preparations containing nonoxynol-9 (N-9) are at a high risk for sexually transmitted diseases, including HIV. Therefore, there is a great interest in identifying compounds that can specifically inhibit sperm without damaging the vaginal lining, possess a powerful spermicide activity, and can be used in contraceptive vaginal preparations to replace N-9. In this work, we studied the spermostatic and/or spermicidal activity of five non-detergent, disulfide compounds on human sperm, HeLa cells, and Lactobacillus acidophilus.

The laminin-induced acrosome reaction in human sperm is mediated by Src kinases and the proteasome.

The aim of this work was to determine whether laminin (Ln), an extracellular matrix protein, induces the intracellular events that may be involved in producing the acrosome reaction in human sperm. To this end, we evaluated the effect of Ln on tyrosine phosphorylation, intracellular calcium concentration, proteasome activity, and phosphorylation in human sperm. Aliquots of highly motile sperm selected with a Percoll gradient, were incubated with different concentrations of Ln (0-20 μg/ml) for different periods (0-18 h).

The effect of an autologous cellular gel-matrix integrated implant system on wound healing.

Background: This manuscript reports the production and preclinical studies to examine the tolerance and efficacy of an autologous cellular gel-matrix integrated implant system (IIS) aimed to treat full-thickness skin lesions.

Methods: The best concentration of fibrinogen and thrombin was experimentally determined by employing 28 formula ratios of thrombin and fibrinogen and checking clot formation and apparent stability. IIS was formed by integrating skin cells by means of the in situ gelification of fibrin into a porous crosslinked scaffold composed of chitosan, gelatin and hyaluronic acid.

Participation of the human sperm proteasome in the capacitation process and its regulation by protein kinase A and tyrosine kinase.

The proteasome is a multicatalytic cellular complex present in human sperm that plays a significant role during several steps of mammalian fertilization. Here, we present evidence that the proteasome is involved in human sperm capacitation. Aliquots of highly motile sperm were incubated with proteasome inhibitors MG132 or epoxomicin.

The role of sperm proteasomes during sperm aster formation and early zygote development: implications for fertilization failure in humans.

BACKGROUND Sperm aster organization during bovine and human fertilization requires a paternally-derived centriole that must first disengage from the sperm tail connecting-piece. We investigated the participation of the 26S proteasome in this process. METHODS Proteasome localization and enzymatic activity were studied in normal and pathological human spermatozoa by immunocytochemistry and enzyme-substrate assays.

Proteasome activity and its relationship with protein phosphorylation during capacitation and acrosome reaction in human spermatozoa.

We have shown that the proteasome is present in mammalian sperm and plays a role during fertilisation. In this work we studied the relationship between protein phosphorylation and proteasomal activity in human sperm. Aliquots of motile sperm were incubated for 0, 5 and 18 h at 37 degrees C, 5% CO2, with different concentration of the kinase inhibitors genistein, H89 or tamoxifen.

Effect of fibronectin on proteasome activity, acrosome reaction, tyrosine phosphorylation and intracellular calcium concentrations of human sperm.

Background: Previously we showed that the human sperm proteasome plays significant roles during mammalian fertilization. Here we studied the effect of fibronectin (Fn), an extracellular matrix protein present in the cumulus oophorus of the oocyte, on proteasome activity, acrosome reaction, intracellular calcium concentration ([Ca(2+)](i)) and protein tyrosine phosphorylation of human sperm.

Methods: Aliquots of motile sperm were incubated for 15 min (T0), 5 h (T5) and 18 h (T18), at 37 degrees C, 5% CO(2) and 95% air with Fn (0-100 microg/ml).

Role of the sperm proteasome during fertilization and gamete interaction in the mouse.

In this work, we have investigated the role of the sperm proteasome during in vitro fertilization (IVF) and gamete interaction in the mouse. Proteasome activity was measured in extract and intact sperm using a specific substrate. In addition, sperm were treated with specific proteasome inhibitors and evaluated during IVF, binding to the zona pellucida, and progesterone- and zona pellucida-induced acrosome reactions.

Proteasomal activity in mammalian spermatozoa.

The proteasome is a multicatalytic cellular complex, which possess three different enzymatic activities, trypsin-like, chymotrypsin-like, and peptidylglutamyl peptidase. Its function is to remove abnormal or aged proteins. Recently, it has been suggested the participation of the sperm proteasome during mammalian fertilization.

Extracellular localization of proteasomes in human sperm.

The proteasome, a multienzymatic protease complex is present in human sperm. Here we present evidence indicating that the proteasome has an extracellular localization, on the plasma membrane of the sperm head. Motile sperm (>90%) in PBS were incubated with the proteasome inhibitors clasto-lactacystin beta-lactone or epoxomicin.

Effect of azorellanone, a diterpene from Azorella yareta Hauman, on human sperm physiology.

Previous studies have shown that cyclic terpenes extracted from plants decrease sperm motility and concentration in rats. In this work, we studied the effect 13-alpha-hydroxy-7-oxoazorellano (azorellanone), a cyclic diterpene extracted from Azorella yareta Hauman, on in vitro human sperm physiology. Sperm aliquots, capacitated for 4.

Participation of the sperm proteasome in human fertilization.

Background: Fertilization in mammals comprises the sequential interactions of the sperm with the cumulus oophorus, zona pellucida, and oocyte plasma membrane. Here we investigate proteasome activity in human sperm and its possible involvement during the fertilization process.

Methods: Proteasome activity was measured in intact sperm and in sperm extracts using the fluorogenic substrate Suc-Leu-Leu-Val-Tyr-AMC, in the presence or absence of the specific proteasome inhibitor, clasto-lactacystin beta-lactone.