Endocannabinoids and Kisspeptins: Two Modulators in Fight for the Regulation of GnRH Activity

The master system in the control of reproductive functions is the communication into the hypothalamus-pituitary-gonadal axis (HPG), whose main actor is the hypothalamic gonadotropin releasing hormone (GnRH). Such a decapeptide triggers the release of pituitary gonadotropins [Follicular Stimulating Hormone (FSH) and Luteinizing Hormone (LH)] which in turn reach the gonads, induce the biosynthesis of steroids (mainly testosterone in males and estradiol/progesterone in females) and of other non steroidal substances (i.e. activin, follistastin, inhibin) modulating the gametogenesis in both sexes. In the last decades, a significant upsurge of studies aimed to define seveal actors and mechanisms supporting reproductive activity. Ultra short, short and long feedback in HPG communication finely modulate reproduction. Nevertheless, this picture is still puzzling and the complete knowledge of the full process has to be unravelled

Estrogens and Spermiogenesis: New Insights from Type 1 Cannabinoid Receptor Knockout Mice

Spermatogenesis is a complex mechanism which allows the production of male gametes; it consists of mitotic, meiotic, and differentiation phases. Spermiogenesis is the terminal differentiation process during which haploid round spermatids undergo several biochemical and morphological changes, including extensive remodelling of chromatin and nuclear shape. Spermiogenesis is under control of endocrine, paracrine, and autocrine factors, like gonadotropins and testosterone. More recently, emerging pieces of evidence are suggesting that, among these factors, estrogens may have a role. To date, this is a matter of debate and concern because of the agonistic and antagonistic estrogenic effects that environmental chemicals may have on animal and human with damaging outcome on fertility. In this review, we summarize data which fuel this debate, with a particular attention to our recent results, obtained using type 1 cannabinoid receptor knockout male mice as animal model

Intra-Testicular Signals Regulate Germ Cell Progression and Production of Qualitatively Mature Spermatozoa in Vertebrates

Spermatogenesis, a highly conserved process in vertebrates, is mainly under the hypothalamic-pituitary control, being regulated by the secretion of pituitary gonadotropins, FSH and LH, in response to stimulation exerted by Gonadotropin Releasing Hormone (GnRH) from hypothalamic neurons. At testicular level, gonadotropins bind specific receptors located on the somatic cells regulating the production of steroids and factors necessary to ensure a correct spermatogenesis. Indeed, besides the endocrine route, a complex network of cell-to-cell communications regulates germ cell progression, and a combination of endocrine and intragonadal signals sustains the production of high quality mature spermatozoa. In this review we focus on the recent advances in the area of the intragonadal signals supporting sperm development.<br/

Nuclear size as estrogen-responsive chromatin quality parameter of mouse spermatozoa.

Recently, we have investigated the endocannabinoid involvement in chromatin remodeling events occurring in male spermatids. Indeed, we have demonstrated that genetic inactivation of the cannabinoid receptor type 1 (Cnr1) negatively influences chromatin remodeling mechanisms, by reducing histone displacement and indices of sperm chromatin quality (chromatin condensation and DNA integrity). Conversely, Cnr1 knock-out (Cnr1-/-) male mice, treated with estrogens, replaced histones and rescued chromatin condensation as well as DNA integrity. In the present study, by exploiting Cnr1+/+, Cnr+/- and Cnr1-/- epididymal sperm samples, we show that histone retention directly correlates with low values of sperm chromatin quality indices determining sperm nuclear size elongation. Moreover, we demonstrate that estrogens, by promoting histone displacement and chromatin condensation rescue, are able to efficiently reduce the greater nuclear length observed in Cnr1-/- sperm. As a consequence of our results, we suggest that nucleus length may be used as a morphological parameter useful to screen out spermatozoa with low chromatin quality

Implementasi Pembelajaran Scientific Berbasis Open Ended Untuk Meningkatkan Kemampuan Berpikir Kreatif Matematika Siswa Pada Materi Penyajian Data Kelas VII F SMP N 3 Sawit Boyolali

The purpose of this research is to improve the ability of student mathematical creative thinking students on material data presentation class VII F SMP N 3 Sawit, Boyolali through Scientific Learning based on Open Ended. This type of research is action class research. Data collection techniques using sheets of observation, field notes sheets, tests, and documentation. Data analysis techniques using data collection, data reduction, data display, and conclusions. The results showed an increase the ability of student mathematical creative thinking with indicator: 1) the ability to generate many answers before there are action as many as 23.33%, and after action as many as 73.33%. 2) the ability to give a uniform answer but with different thinking (a different way) before the action of 23.33%, and after the action of 73.33%. 3) ability to generate strategies (ways of completion) before the action of 16.67%, and after the action of 63.33%. 4) ability to explain and detail the answers before the action of 23.33%, and after the action of 46.67%

Author Correction: The role of presepsin in pediatric patients with oncological and hematological diseases experiencing febrile neutropenia

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Differential Expression of Kisspeptin System and Kisspeptin Receptor Trafficking during Spermatozoa Transit in the Epididymis

The hypothalamus–pituitary–testis axis controls the production of spermatozoa, and the kisspeptin system, comprising Kiss1 and Kiss1 receptor (Kiss1R), is the main central gatekeeper. The activity of the kisspeptin system also occurs in testis and spermatozoa, but currently the need of peripheral kisspeptin to produce gametes is not fully understood. Hence, we characterized kisspeptin system in rat spermatozoa and epididymis caput and cauda and analyzed the possible presence of Kiss1 in the epididymal fluid. The presence of Kiss1 and Kiss1R in spermatozoa collected from epididymis caput and cauda was evaluated by Western blot; significant high Kiss1 levels in the caput (p < 0.001 vs. cauda) and constant levels of Kiss1R proteins were observed. Immunofluorescence analysis revealed that the localization of Kiss1R in sperm head shifts from the posterior region in the epididymis caput to perforatorium in the epididymis cauda. In spermatozoa-free epididymis, Western blot revealed higher expression of Kiss1 and Kiss1R in caput (p < 0.05 vs. cauda). Moreover, immunohistochemistry revealed that Kiss1 and Kiss1R proteins were mainly localized in the secretory epithelial cell types and in contractile myoid cells, respectively. Finally, both dot blot and Elisa revealed the presence of Kiss1 in the epididymal fluid collected from epididymis cauda and caput, indicating that rat epididymis and spermatozoa possess a complete kisspeptin system. In conclusion, we reported for the first time in rodents Kiss1R trafficking in spermatozoa during the epididymis transit and Kiss1 measure in the epididymal fluid, thus suggesting a possible role for the system in spermatozoa maturation and storage within the epididymis

The role of presepsin in pediatric patients with oncological and hematological diseases experiencing febrile neutropenia

Febrile neutropenia (FN) represents one of the main complications of pediatric patients with oncological and hematological diseases. In these patients, it is crucial to identify bacterial infections. The aim of this study is to evaluate presepsin as an early biomarker of bacterial infections during FN. We compared patients with oncological and hematological diseases and a 2:1 age-matched healthy control group. In the FN group, we evaluated 4 biomarkers, namely, C reactive protein (CRP), procalcitonin (PCT), interleukin 6 (IL6) and presepsin at the onset of fever (T0) and 48 h after T0 (T1). In the control group, we only evaluated presepsin. We enrolled a total of 41 children with oncological and hematological diseases disease experiencing 50 FN episodes and 100 healthy patients in the control group. In patients with FN, we found that presepsin was significantly higher than in the control group (p &lt; 0.001). However, in the FN group, we did not find a statistically significant difference between patients with and without bacteremia (p = 0.989 at T0, p = 0.619 at T1). Presepsin values at T1 were higher in patients experiencing an unfavorable outcome (p = 0.025). This study shows that presepsin increases in neutropenic patients, but it only revealed useful in predicting an unfavorable outcome 48 h from the onset of fever