Glucocorticoids improve sperm performance in physiological and pathological conditions: their role in sperm fight/flight response.

Glucocorticoids play a physiologic role in the adult male reproductive functions, modulating gonadal steroid synthesis and spermatogenesis, through the glucocorticoid receptor (GR). The expression of GR has been described in several key testicular cell types, including somatic cells and early germ cell populations. Nothing is known on GR in human spermatozoa.

Leptin effects: focusing on the relationship between obesity and male infertility.

The human male infertility has several causes interconnected to improper lifestyles such as smoking, sedentarism, environmental factors, toxins accumulation and energy imbalances. All these factors contribute to the obesity accompanied metabolic syndrome and hormonal alterations in the leptin-ghrelin axis. The leptin (Lep) has many pleiotropic effects in several biological systems, directly on the peripheral tissues or through the central nervous system.

Glucagon-like peptide-1 receptor is expressed in human and rodent testis.

Background: The incretin hormone glucagon-like peptide-l (GLP-1) is an important regulator of post-prandial insulin secretion, acting through a G protein-coupled cell surface receptor (GLP-1R). In addition to its expression in pancreatic β-cells, several studies suggested that GLP-1R is located in extra-pancreatic tissues.

Objectives: In this study, we examined for the first time the testicular distribution of the GLP-1R, both in normal human and neoplastic testicular tissues as well as in rodent testis and rodent testicular cell lines.

FSH-R Human Early Male Genital Tract, Testicular Tumors and Sperm: Its Involvement in Testicular Disorders.

The follicle-stimulating hormone receptor (FSH-R) expression was always considered human gonad-specific. The receptor has also been newly detected in extragonadal tissues. In this finding, we evaluated FSH-R expression in the human male early genital tract, in testicular tumors, and in sperm from healthy and varicocele patients.

Sperm performance in oligoasthenoteratozoospermic patients is induced by a nutraceuticals mix, containing mainly myo-inositol.

The action of myo-inositol (MI), belonging to the inositol family, has been shown to improve sperm quality. To further elucidate the efficacy of this substance in male fertility, we investigated the effects of a nutraceuticals mix, containing mainly myo-inositol (MI) and the action of the MI on human male gamete performance. Sperm samples were evaluated from 51 men: 21 healthy normozoospermic and 30 oligoasthenoteratozoospermic (OAT).

Peroxisome proliferator-activated receptor gamma expression along the male genital system and its role in male fertility.

Peroxisome proliferator-activated receptor gamma (PPARγ) acts as a ligand activated transcription factor and regulates processes, such as energy homeostasis, cell proliferation and differentiation. PPARγ binds to DNA as a heterodimer with retinoid X receptor and it is activated by polyunsaturated fatty acids and fatty acid derivatives, such as prostaglandins. In addition, the insulin-sensitizing thiazolidinediones, such as rosiglitazone, are potent and specific activators of PPARγ.

The Tumor Suppressor as Molecular Switch Node Regulating Cell Metabolism and Autophagy: Implications in Immune System and Tumor Microenvironment.

Recent studies conducted over the past 10 years evidence the intriguing role of the tumor suppressor gene Phosphatase and Tensin Homolog deleted on Chromosome 10 in the regulation of cellular energy expenditure, together with its capability to modulate proliferation and survival, thus expanding our knowledge of its physiological functions. Transgenic mice models are resistant to oncogenic transformation, present decreased adiposity and reduced cellular glucose and glutamine uptake, together with increased mitochondrial oxidative phosphorylation. These acquisitions led to a novel understanding regarding the role of to counteract cancer cell metabolic reprogramming.

Human Sperm Express the Receptor for Glucagon-like Peptide-1 (GLP-1), Which Affects Sperm Function and Metabolism.

Aim: Glucagon-like peptide-1 (GLP-1) produces pleiotropic effects binding to the GLP-1 receptor (GLP1-R), potentiating insulin secretion in the pancreas. GLP1-R is expressed in peripheral tissues and evidence for its role in reproduction has come from knockout mice, although the relationship between GLP-1 and male fertility needs to be clarified. Given that human sperm is an insulin-sensitive and insulin-secreting cell, we hypothesized that the GLP-1/GLP1-R axis may be expressed and functional in these cells.

Progesterone Receptor B signaling Reduces Breast Cancer Cell Aggressiveness: Role of Cyclin-D1/Cdk4 Mediating Paxillin Phosphorylation.

Progesterone-Receptor (PR) positivity is related with an enhanced response to breast cancer therapy, conversely cyclin D1 (CD1) is a retained marker of poor outcome. Herein, we demonstrate that hydroxyprogesterone (OHPg) through progesterone receptor B (PR-B) reduces breast cancer cell aggressiveness, by targeting the cytoplasmic CD1. Specifically, OHPg diminishes CD1 expression by a transcriptional regulation due to the recruitment of PR-B at a canonical half-PRE site of the CD1 promoter, together with HDAC1, determining a chromatin conformation less prone for gene transcription.

Leptin Receptor as a Potential Target to Inhibit Human Testicular Seminoma Growth.

Although in past decades the adipokine leptin and its own receptor have been considered as significant cancer biomarkers, their potential involvement in human testicular seminoma growth and progression remains unexplored. Here, we showed that the expression of leptin and its receptor was significantly higher in human testicular seminoma compared with normal adult testis. Human seminoma cell line TCam-2 also expressed leptin along with the long and short isoforms of leptin receptor, and in response to leptin treatment showed enhanced activation of its downstream effectors.

Influence of all-trans retinoic acid on sperm metabolism and oxidative stress: Its involvement in the physiopathology of varicocele-associated male infertility.

The mechanisms by which varicocele affects fertility remain undetermined. Vitamin A (all-trans retinoic acid [ATRA]) is required for fertility and normal spermatogenesis; however, the mechanisms driving its action are not defined yet. Previously, we demonstrated in varicocele sperm a reduced RARα expression and that ATRA influence sperm performance.

Immunolocalization of G Protein-Coupled Estrogen Receptor in the Pig Epididymis.

The presence of estrogen in the genital ducts of different mammalian species has been extensively studied and the estrogen influence on the functional activity of the male genital tract has been hypothesized. Conversely, very few data have been reported on pig excurrent ducts: the localization of classical estrogen receptors (ERα and ERβ) is scarcely known, while the expression of the G protein-coupled receptor (GPER1), a membrane estrogen receptor, is still unknown in pig. The aim of the present study was to evaluate GPER1 expression in the different regions of the mature pig epididymis, using immunohistochemistry, western blot and RT-PCR analyses.

FoxO3a Mediates the Inhibitory Effects of the Antiepileptic Drug Lamotrigine on Breast Cancer Growth.

Breast cancer is a complex and heterogeneous disease, with distinct histologic features dictating the therapy. Although the clinical outcome of breast cancer patients has been considerably improved, the occurrence of resistance to common endocrine and chemotherapy treatments remains the major cause of relapse and mortality. Thus, efforts in identifying new molecules to be employed in breast cancer therapy are needed.

Estradiol via estrogen receptor beta influences ROS levels through the transcriptional regulation of SIRT3 in human seminoma TCam-2 cells.

Human testis, gonocytes, and adult germ cells mainly express estrogen receptor beta, and estrogen receptor beta loss is associated with advanced tumor stage; however, the molecular mechanisms of estrogen receptor beta-protective effects are still to be defined. Herein, we provide evidence that in human seminoma TCam-2 cells, E2 through estrogen receptor beta upregulates the mitochondrial deacetylase sirtuin-3 at protein and messenger RNA levels. Specifically, E2 increases sirtuin-3 expression through a transcriptional mechanism due to the occupancy of sirtuin-3 promoter by estrogen receptor beta, together with the transcription factor Sp1 as evidenced by Chip reChIp assay.

Ligand activated progesterone receptor B drives autophagy-senescence transition through a Beclin-1/Bcl-2 dependent mechanism in human breast cancer cells.

Loss of progesterone-receptors (PR) expression is associated with breast cancer progression. Herein we provide evidence that OHPg/PR-B through Beclin-1 evoke autophagy-senescence transition, in breast cancer cells. Specifically, OHPg increases Beclin-1 expression through a transcriptional mechanism due to the occupancy of Beclin-1 promoter by PR-B, together with the transcriptional coactivator SRC-2.

Steroid receptors in human ejaculated sperm as molecular markers of the detrimental effects related to the pathophysiology of testicular varicocele.

The exact physiopathologic effect of testicular varicocele on male fertility is not defined yet. The detrimental role of the varicocele in fertility is supported by the presence of a higher frequency of affected men among the infertile population. However, the mechanism/s by which a varicocele impairs sperm production, structure and function, is not known.

Exosomes in human atherosclerosis: An ultrastructural analysis study.

Cell-to-cell communication, or signaling, is absolutely essential in orchestrating the activities of cells in multicellular organisms, to grow, develop, detect environmental changes and compensate for them in an internal, coordinated fashion. In the last few years, a considerable amount of new data have demonstrated the occurrence of a sophisticated intercellular signaling pathway based on the release of specialized vesicular structures, called exosomes, whose secretion appears to be regulated by various natural and experimental stimuli, physiological states, and disease processes. In the cardiovascular system, the study of exosomes is still in its infancy.

Recombinant Arabidopsis HSP70 Sustains Cell Survival and Metastatic Potential of Breast Cancer Cells.

The chaperone HSP70 protein is widely present in many different tumors and its expression correlates with an increased cell survival, low differentiation, and poor therapeutic outcome in human breast cancer. The intracellular protein has prevalently a cytoprotective function, while the extracellular HSP70 mediates immunologic responses. Evolutionarily, HSPs are well conserved from prokaryotes to eukaryotes, and human HSP70 shows a strong similarity to that of plant origin.

Androgens downregulate miR-21 expression in breast cancer cells underlining the protective role of androgen receptor.

Although the protective role of androgen receptor (AR) in breast cancer (BC) is well established, the mechanisms involved remains largely unexplored. MicroRNAs play fundamental roles in many biological processes, including tumor cell development and metastasis. Herein, we report that androgens reduce BC cells proliferation acting as a negative modulator of the onco-miRNA-21.

Bergapten induces metabolic reprogramming in breast cancer cells.

Alterations in cellular metabolism are among the most consistent hallmarks of cancer. Herein, after a comprehensive metabolic phenotype characterization of MCF7 and ZR75 breast cancer cells, we investigated the activity of bergapten (Bg), a plant-derived compound, against breast cancer. The study of different biochemical pathways involved in cell metabolism revealed that the two cell lines have different bioenergetic phenotypes: MCF7 cells express a glycolytic phenotype only partially oxidative, while ZR75 cells mainly have an oxidative phenotype.

Human sperm liver receptor homolog-1 (LRH-1) acts as a downstream target of the estrogen signaling pathway.

In the last decade, the study of human sperm anatomy, at molecular level, has revealed the presence of several nuclear protein receptors. In this work, we examined the expression profile and the ultrastructural localization of liver receptor homolog-1 (LRH-1) in human spermatozoa. We evidenced the presence of the receptor by Western blotting and real time-RT-PCR.