Dendrobium nobile Lindl polysaccharides improve testicular spermatogenic function in streptozotocin-induced diabetic rats.

Dendrobium nobile Lindl polysaccharides (DNLP) exhibited various biological functions. This study aimed to investigate the protective effects of DNLP on testicular spermatogenic function in streptozotocin (STZ)-induced diabetic rats in comparison with metformin. The blood glucose level was significantly increased and the homeostatic model assessment for insulin resistance (HOMA-IR) aggravated markedly in diabetic rats. The weight of testis and epididymis, and the sperm number and motility were decreased in the diabetic rats. The pathologic changes occurred in the spermatogenic tubules along with the decreased number of spermatogenic cells, downregulated proliferating cell nuclear antigen (PCNA) and Sirtuin 1 (SIRT1) expression and increased cell apoptosis in the testes. Compared with the model group, DNLP and metformin treatment significantly decreased the level of blood glucose, improved the HOMA-IR, and increased the weight of testis and epididymis, as well as the sperm number and sperm motility. Furthermore, the pathologic changes in the spermatogenic tubules improved significantly with increased number of spermatogenic cells, the upregulation of PCNA and SIRT1 and suppression of cell apoptosis in the testes. Collectively, our study for the first time examined the effects of DNLP on the male reproductive system of STZ-induced diabetic rats, and indicated that DNLP was protective against diabetes mellitus-induced testis injury via increasing the proliferation, inhibiting cell apoptosis and upregulating SIRT1 expression in testicular spermatogenic cells.

The Role of the PI3K/AKT/mTOR Signalling Pathway in Male Reproduction.

Male fertility is closely related to the normal function of the hypothalamicpituitary- testicular axis. The testis is an important male reproductive organ that secretes androgen and produces sperm through spermatogenesis. Spermatogenesis refers to the process by which spermatogonial stem cells (SSCs) produce highly differentiated spermatozoa and is divided into three stages: mitosis, meiosis and spermiogenesis. Spermatogenesis requires SSCs to strike a proper balance between self-renewal and differentiation and the commitment of spermatocytes to meiosis, which involves many molecules and signalling pathways. Abnormal gene expression or signal transduction in the hypothalamus and pituitary, but particularly in the testis, may lead to spermatogenic disorders and male infertility. The phosphoinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway is involved in many stages of male reproduction, including the regulation of the hypothalamus-pituitarygonad (HPG) axis during spermatogenesis, the proliferation and differentiation of spermatogonia and somatic cells, and the regulation of sperm autophagy and testicular endocrine function in the presence of environmental pollutants, particularly endocrinedisrupting chemicals (EDCs). In the PI3K/AKT/mTOR signalling pathway, mTOR is considered the central integrator of several signals, regulating metabolism, cell growth and proliferation. In particular, mTOR plays an important role in the maintenance and differentiation of SSCs, as well as in regulating the redox balance and metabolic activity of Sertoli cells, which play an important role in nutritional support during spermatogenesis.

Polycystic ovarian syndrome: Correlation between hyperandrogenism, insulin resistance and obesity.

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease characterized by clinical or laboratorial hyperandrogenism, oligo-anovulation and metabolic abnormalities, including insulin resistance, excessive weight or obesity, type II diabetes, dyslipidemia and an increased risk of cardiovascular disease. The most significant clinical manifestation of PCOS is hyperandrogenism. Excess androgen profoundly affects granulosa cell function and follicular development via complex mechanisms that lead to obesity and insulin resistance. Most PCOS patients with hyperandrogenism have steroid secretion defects that result in abnormal folliculogenesis and failed dominant follicle selection. Hyperandrogenism induces obesity, hairy, acne, and androgenetic alopecia. These symptoms can bring great psychological stress to women. Drugs such as combined oral contraceptive pills, metformin, pioglitazone and low-dose spironolactone help improve pregnancy rates by decreasing androgen levels in vivo. Notably, PCOS is heterogeneous, and hyperandrogenism is not the only pathogenic factor. Obesity and insulin resistance aggravate the symptoms of hyperandrogenism, forming a vicious cycle that promotes PCOS development. Although numerous studies have been conducted, the definitive pathogenic mechanisms of PCOS remain uncertain. This review summarizes and discusses previous and recent findings regarding the relationship between hyperandrogenism, insulin resistance, obesity and PCOS.

Dyslipidemia involvement in the development of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is widely accepted as the most common endocrine abnormality in women of childbearing age and may be accompanied by dyslipidemia, hyperandrogenism, hyperinsulinemia, oxidative stress and infertility. Dyslipidemia is now known to play an important role in the development of PCOS. Lipid abnormalities, including elevated low-density lipoprotein and triglyceride levels and reduced high-density lipoprotein levels, are often found in women with PCOS and play an important role in PCOS; therefore, we summarize the effect of lipid abnormalities on hyperandrogenism, insulin resistance, oxidative stress and infertility in PCOS and review the effects of common lipid-lowering drugs on patients with PCOS. The purpose of this article is to elucidate the mechanisms of lipid metabolism abnormalities in the development of PCOS.

The roles of retinoic acid in the differentiation of spermatogonia and spermatogenic disorders.

Male fertility depends on the regulatory balance between germ cell self-renewal and differentiation, and the spatial and temporal patterns of this balance must be maintained throughout the life cycle. Retinoic acid and its receptors are important factors in spermatogenesis. Spermatogonia cells can self-proliferate and differentiate and have unique meiotic capabilities; they halve their genetic material and produce monomorphic sperm to pass genetic material to the next generation. A number of studies have found that the spermatogenesis process is halted in animals with vitamin A deficiency and that most germ cells are degraded, but they tend to recover after treatment with RA or vitamin A. This literature review discusses our understanding of how RA regulates sperm cell differentiation and meiosis and also reviews the functional information and details of RA.

Nogo­B receptor in relevant carcinoma: Current achievements, challenges and aims (Review).

The novel neurite outgrowth inhibitor B (Nogo­B) receptor (NgBR) is specific for Nogo­B, which is highly expressed in various human organs and cells, including the lung, liver, kidney, smooth muscle cells, blood vessel endothelial cells and inflammatory cells. Previous studies have indicated that NgBR directly interacts with Nogo­B and is able to independently influence lipid and cholesterol homeostasis, angiogenesis, N­glycosylation, the epithelial-mesenchymal transition, the chemotaxis of endothelial cells and cellular proliferation and apoptosis. These multiple functions and actions of this receptor provide an understanding of the important roles of NgBR in various conditions, including fatty liver, atherosclerosis, intracranial microaneurysms, retinitis pigmentosa and severe neurological impairment. Furthermore, NgBR has been demonstrated to exert protean, multifunctional and enigmatic effects in cancer. The present review summarizes the latest knowledge on the suppressing and activating effects of NgBR, emphasizing its function in cancer. Further basic and medical research on this receptor may provide novel insight into its clinical implications on the prognosis of relevant human cancer types.

Characterization of cholesterol metabolism in Sertoli cells and spermatogenesis (Review).

The Sertoli cell, which is the supporting cell of spermatogenesis, has an important role in the endocrine and paracrine control of spermatogenesis. Functionally, it provides the cells of the seminiferous epithelium with nutrition, conveys mature spermatids to the lumen of seminiferous tubules, secretes androgen­binding protein and interacts with endocrine Leydig cells. In addition, the levels of cholesterol, as well as its intermediates, vary greatly between nongonadal tissues and the male reproductive system. Throughout spermatogenesis, a dynamic and constant alteration in the membrane lipid composition of Sertoli cells occurs. In several mammalian species, testis meiosis­activating sterol and desmosterol, as well as other cholesterol precursors, accumulate in the testes and spermatozoa. In addition, certain cholesterogenic genes exhibit stage­specific expression patterns during spermatogenesis, including the cytochrome P450 enzyme lanosterol 14α­demethylase. Inconsistency in the patterns of gene expression during spermatogenesis indicates a cell­type specific and complex temporary modulation of lipids and cholesterol, which also implicates the dynamic interactions between Sertoli cells and germ cells. Furthermore, in the female reproductive tract and during epididymal transit, which is a prerequisite for valid fertilization, the modulation of cholesterol occurring in spermatozoal membranes further indicates the functional importance of sterol compounds in spermatogenesis. However, the exact role of cholesterol metabolism in Sertoli cells in sperm production is unknown. The present review article describes the progress made in the research regarding the characteristics of the Sertoli cell, particularly the regulation of its cholesterol metabolism during spermatogenesis.

Neurite Outgrowth Inhibitor B Receptor: A Versatile Receptor with Multiple Functions and Actions.

Members of the reticulon protein family are predominantly distributed within the endoplasmic reticulum. The neurite outgrowth inhibitor (Nogo) has three subtypes, including Nogo-A (200 kDa), Nogo-B (55 kDa), and Nogo-C (25 kDa). Nogo-A and Nogo-C are potent Nogos that are predominantly expressed in the central nervous system. Nogo-B, the splice variant of reticulon-4, is expressed widely in multiple human organ systems, including the liver, lung, kidney, blood vessels, and inflammatory cells. Moreover, the Nogo-B receptor (NgBR) can interact with Nogo-B and can independently affect nervous system regeneration, the chemotaxis of endothelial cells, proliferation, and apoptosis. In recent years, it has been demonstrated that NgBR plays an important role in human pathophysiological processes, including lipid metabolism, angiogenesis, N-glycosylation, cell apoptosis, chemoresistance in human hepatocellular carcinoma, and epithelial-mesenchymal transition. The pathophysiologic effects of NgBR have garnered increased attention, and the detection and enhancement of NgBR expression may be a novel approach to monitor the development and to improve the prognosis of relevant human clinical diseases.

Involvement of EBV-encoded BART-miRNAs and dysregulated cellular miRNAs in nasopharyngeal carcinoma genesis.

The definite molecular mechanisms underlying the genesis of nasopharyngeal carcinomas (NPCs) remain to be completely elucidated. miRNAs are small non-coding RNAs which are implicated in cell proliferation, apoptosis, and even carcinogenesis through negatively regulating gene expression post-transcriptionally. EBV was the first human virus found to express miRNAs. EBV-encoded BART-miRNAs and dysregulated cellular miRNAs are involved in carcinogenesis of NPC by interfering in the expression of viral and host cell genes related to immune responses and perturbing signal pathways of proliferation, apoptosis, invasion, metastasis and even radio-chemo-therapy sensitivity. Additional studies on the roles of EBV-encoded miRNAs and cellular miRNAs will provide new insights concerning the complicated gene regulated network and shed light on novel strategies for the diagnosis, therapy and prognosis of NPC.