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

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/

A novel experimental approach for liver analysis in rats exposed to Bisphenol A by means of LC-mass spectrometry and infrared spectroscopy

An innovative complementary approach using a liquid chromatographic-mass spectrometer method and infrared spectroscopy is proposed for measuring internal biological exposure to dangerous chemical contaminants and for monitoring biochemical changes in target organs. The proposed methodologies were validated and applied in the case of rats exposed to low-doses of Bisphenol A (BPA). A liquid chromatographic method coupled to a tandem mass spectrometer was used in order to measure BPA concentration in rat livers. BPA was detected at different levels in all liver samples from BPA-treated rats, although the exposure dose was the same in all treated animals, and also from control rats, highlighting the difficulties in eliminating external uncontrolled exposure and the need for internal biological monitoring. Fourier Transform Infrared analysis was applied to detect structural changes occurring in several molecules (lipids, proteins, carbohydrates and nucleic acids) as well as the presence of specific metabolic processes. The spectroscopic analyses clearly demonstrated a different lipid composition more than an evident lipid accumulation and a glycogen accumulation decrease, revealing a metabolic disturbance in livers with a normal histological aspect. These results demonstrated the potential of an integrated approach based on mass spectrometry and infrared spectroscopy to evaluate at an early stage the hepatotoxic effect of BPA exposure in an animal model. This approach can be usefully exploited in all the investigations aimed to provide better information concerning the interrelationships between contaminant exposure, dose, and health effects

Actin remodeling driven by circLIMA1: sperm cell as an intriguing cellular model

CircRNA cargo in spermatozoa (SPZ) participates in setting cell quality, in terms of morphology and motility. Cannabinoid receptor CB1 activity is correlated with a proper spermatogenesis and epididymal sperm maturation. Despite CB1 promotes endogenous skill to circularize mRNAs in SPZ, few notions are reported regarding the functional link between endocannabinoids and spermatic circRNA cargo. In CB1 knock-out male mice, we performed a complete dataset of spermatic circRNA content by microarray strategy. Differentially expressed (DE)-circRNAs, as a function of genotype, were identified. Within DE-circRNAs, we focused the attention on circLIMA1, as putative actin-cytoskeleton architecture regulator. The validation of circLIMA1 dependent-competitive endogenous RNA (ceRNA) network (ceRNET) in in vitro cell line confirmed its activity in the regulation of the cytoskeletal actin. Interestingly, a dynamic actin regulation in SPZ nuclei was found during their epididymal maturation. In this scenario, we showed for the first time an intriguing sperm nuclear actin remodeling, regulated via a ceRNET-independent pathway, consisting in the nuclear shuttling of circLIMA1-QKI interactome and downstream in Gelsolin regulation. In particular, the increased levels of circLIMA1 in CB1 knock-out SPZ, associated with an inefficient depolymerization of nuclear actin, specifically illustrate how endocannabinoids, by regulating circRNA cargo, may contribute to sperm morpho-cellular maturation