Gonadotropin Cell Transduction Mechanisms

The intention of this Special Edition was to collect review and original research articles that illustrate and stimulate the growing efforts to highlight the mechanisms of action of gonadotropins, as well as deepen our understanding of their biological roles in health and disease, aiming at revealing novel therapeutic opportunities in reproductive and regenerative medicine [...]

The spermatozoa caught in the net: the biological networks to study the male gametes post-ejaculatory life

<p>Abstract</p> <p>Background</p> <p>Mammalian spermatozoa, immediately after the ejaculation are unable to fertilize the oocyte. To reach their fertilizing ability the male gametes must complete a process of functional maturation, the capacitation, within the female genital tract. Only once the capacitation is completed the spermatozoa can respond to the oocyte interaction with the exocytosis of acrosome content, acrosome reaction (AR). These post-ejaculatory events are under the attention of Researchers from more than fifty years but their basic knowledge is still unsatisfactory. This failure could be due not to the insufficiency of available data, but to the inability to manage them in a descriptive model. Thus, to overlap this problem, the capacitation and the AR were represented using the biological networks formalism. In addition the effect of elimination from both the networks of the most linked (the hubs) or of random selected nodes was verified and the network representing the common element of capacitation and AR (C∩A) was realized.</p> <p>Results</p> <p>The statistical analysis of resulting graphs showed that capacitation, AR and C∩A networks follow the scale free topology and are characterized by low clustering. In all cases it was possible to identify the key molecules (Ca²⁺, ATP, P-Tyr, PKA, PLD1 in capacitation, Ca²⁺, ATP in AR and C∩A) and to describe their role in signalling transduction. The effect of hubs elimination caused the collapse of networks structure, while the elimination of random selected nodes did not affected it.</p> <p>Conclusions</p> <p>It was demonstrated that the post-ejaculatory life of male gametes is a series of events characterised by a high signalling efficiency and robustness against random failure. This strengthens the evidence that the adoption of biological networks modellization of capacitation and AR could increase the understanding of spermatozoa physiology, potentially opening new perspective in drug discovery, diagnosis and therapy of male infertility.</p

Cumulus cells steroidogenesis is influenced by the degree of oocyte maturation

BACKGROUND: The possibility to predict the ability of a germ cell to properly sustain embryo development in vitro or in vivo as early as possible is undoubtedly the main problem of reproductive technologies. To date, only the achievement of nuclear maturation and cumulus expansion is feasible, as all the studies on cytoplasmic maturation are too invasive and have been complicated by the death of the cells analyzed. The authors studied the possibility to test the cytoplasmic quality of pig oocytes by evaluating their ability to produce steroidogenesis enabling factor(s). To this aim, oocytes matured under different culture conditions that allowed to obtain gradable level of cytoplasmic maturation, were used to produce conditioned media (OCM). The secretion of the factor(s) in conditioned media was then recorded by evaluating the ability of the spent media to direct granulosa cells (GC) steroidogenesis. METHODS: In order to obtain germ cells characterized by a different degree of developmental competence, selected pig oocytes from prepubertal gilts ovaries were cultured under different IVM protocols; part of the matured oocytes were used to produce OCM, while those remaining were submitted to in vitro fertilization trials to confirm their ability to sustain male pronuclear decondensation. The OCM collected were finally used on cumulus cells grown as monolayers for 5 days. The demonstration that oocytes secreted factor(s) can influence GC steroidogenesis in the pig was confirmed in our lab by studying E(2 )and P(4 )production by cumulus cells monolayers using a radioimmunoassay technique. RESULTS: Monolayers obtained by growing GC surrounding the oocytes for five days represent a tool, which is practical, stable and available in most laboratories; by using this bioassay, we detected the antiluteal effect of immature oocytes, and for the first time, demonstrated that properly matured germ cells are able to direct cumulus cells steroidogenesis by inhibiting E(2 )production (P < 0.01). Nevertheless, only fully competent oocytes were able to suppress estrogens production, while those cultured under unfavourable conditions were unable to exert any inhibitory effect on the functions of cumulus cells (P < 0.01). CONCLUSION: These results demonstrated that good quality oocytes can be easily selected on the basis of their ability to affect granulosa cell steroidogenesis thus reducing failures in reproductive technologies due to the transfer of fertilized oocytes with a scarce ability to sustain embryo development

Networks Models of Actin Dynamics during Spermatozoa Postejaculatory Life: A Comparison among Human-Made and Text Mining-Based Models

Here we realized a networks-based model representing the process of actin remodelling that occurs during the acquisition of fertilizing ability of human spermatozoa (HumanMade_ActinSpermNetwork, HM_ASN). Then, we compared it with the networks provided by two different text mining tools: Agilent Literature Search (ALS) and PESCADOR. As a reference, we used the data from the online repository Kyoto Encyclopaedia of Genes and Genomes (KEGG), referred to the actin dynamics in a more general biological context. We found that HM_ALS and the networks from KEGG data shared the same scale-free topology following the Barabasi-Albert model, thus suggesting that the information is spread within the network quickly and efficiently. On the contrary, the networks obtained by ALS and PESCADOR have a scale-free hierarchical architecture, which implies a different pattern of information transmission. Also, the hubs identified within the networks are different: HM_ALS and KEGG networks contain as hubs several molecules known to be involved in actin signalling; ALS was unable to find other hubs than “actin,” whereas PESCADOR gave some nonspecific result. This seems to suggest that the human-made information retrieval in the case of a specific event, such as actin dynamics in human spermatozoa, could be a reliable strategy

improving delivery and offspring viability of in vitro produced and cloned sheep embryos

Recently developed, assisted reproductive technologies (e.g., in vitro embryo production and nuclear transfer) have encountered perinatal morbidity/mortality of the offspring produced, which are likely to hinder the application of these techniques. Consequently we have sought to develop a system of hormonal stimulation that will ensure the delivery of offspring more prepared for extrauterine life. Here we examine deliveries outcome in sheep carrying in vitro-produced and nuclear transfer (NT) embryos in comparison to artificially inseminated and naturally mated control ewes. All groups (excluding NT, which received one treatment) were subjected to one of two hormonal treatments for induction of delivery, whereas the third part of each group was left without any treatment. The first (commonly used for naturally mated ewes) dexamethasone treatment did not solve a majority of parturition disturbances, and actually the number of deliveries necessitating assistance was reduced (P < 0.05) by this treatment in the control group. On the other hand, combined estradiol plus betamethasone stimulation (E + B) solved a majority of complications regarding delivery performance such as lack of the preparation of the mammary gland, low myometrial contractility, insufficient cervical ripening, and impaired maternal behavior. Moreover, substantial reduction of neonatal mortality was observed following the combined treatment. In conclusion, the E + B induction of delivery overcame the majority of physiological and behavioral intrapartum failures of sheep foster mothers and increased the survival of offspring, and thus can be recommended as a safe method for inducing delivery in foster mothers carrying in vitro-generated embryos

Amniotic Epithelial Cells: A New Tool to Combat Aging and Age-Related Diseases?

The number of elderly people is growing at an unprecedented rate and this increase of the aging population is expected to have a direct impact on the incidence of age-related diseases and healthcare-associated costs. Thus, it is imperative that new tools are developed to fight and slow age-related diseases. Regenerative medicine is a promising strategy for the maintenance of health and function late in life; however, stem cell-based therapies face several challenges including rejection and tumor transformation. As an alternative, the placenta offers an extraordinary source of fetal stem cells, including the amniotic epithelial cells (AECs), which retain some of the characteristics of embryonic stem cells, but show low immunogenicity, together with immunomodulatory and anti-inflammatory activities. Because of these characteristics, AECs have been widely utilized in regenerative medicine. This perspective highlights different mechanisms triggered by transplanted AECs that could be potentially useful for anti-aging therapies, which include: Graft and differentiation for tissue regeneration in age-related settings, anti-inflammatory behavior to combat inflammaging, anti-tumor activity, direct lifespan and healthspan extension properties, and possibly rejuvenation in a manner reminiscent of heterochronic parabiosis.Here, we critically discuss benefits and limitation of AECs-based therapies in age-related diseases

Can this be considered a Fondaparinux-induced Thrombocytopenia?

We present a case of an old woman with previously documented heparin-induced thrombocytopenia (HIT), treated with fondaparinux, who presented with thrombocytopenia and venous thrombosis after exposure to a preventive dose of fondaparinux during orthopaedic surgery. Any accidental exposure to heparin was avoided. Other causes of thrombocytopenia were excluded and antigenic tests combined with clinical probability made a diagnosis of HIT likely. Can this be considered a possible case of fondaparinux-related HIT, despite the intense and early decrease in platelets, as usually happens in rapid-onset HIT, and the fact that previous exposure to fondaparinux had occurred 5 months previously

Chapter Membrane Dynamics of Spermatozoa during Capacitation: New Insight in Germ Cells Signalling

The study of germline stem cells and of germline cells has deep implications for the understanding of fertility, development and cancer. Nowadays, we are experiencing the very fascinating challenge of application of –OMICS technologies to this issue, which is opening new and unexpected horizons in virtually all the branches of biology. Here, we carried out a review of signalling systems involved in maturation of male germ cells and in the process that leads them to become fully fertile. In particular, we discuss the control mechanisms involved in capacitation and acrosome reaction that act at membrane level. Indeed, spermatozoa membranes play key roles in determining the achievement of fertility: they are the interface with the surrounding environment, they locate the signal transduction systems and they are active in recognizing and binding the oocyte. In addition, we discuss the effect of several compounds that could exert a negative effect on reproductive activity, by interfering with the endocrine axis, the so-called endocrine disruptors

Graphene and Reproduction: A Love-Hate Relationship

Since its discovery, graphene and its multiple derivatives have been extensively used in many fields and with different applications, even in biomedicine. Numerous efforts have been made to elucidate the potential toxicity derived from their use, giving rise to an adequate number of publications with varied results. On this basis, the study of the reproductive function constitutes a good tool to evaluate not only the toxic effects derived from the use of these materials directly on the individual, but also the potential toxicity passed on to the offspring. By providing a detailed scientometric analysis, the present review provides an updated overview gathering all the research studies focused on the use of graphene and graphene-based materials in the reproductive field, highlighting the consequences and effects reported to date from experiments performed in vivo and in vitro and in different animal species (from Archea to mammals). Special attention is given to the oxidized form of graphene, graphene oxide, which has been recently investigated for its ability to increase the in vitro fertilization outcomes. Thus, the potential use of graphene oxide against infertility is hypothesized here, probably by engineering the spermatozoa and thus manipulating them in a safer and more efficient way