Phosphatidylserine (PS) is an amphiphilic phospholipid ubiquitously present in the inside of the membrane of prokaryotic and eukaryotic cells. In mammalian cells, there are two synthetic pathways for PS that are different from those of bacterial biosynthesis. The translocation of sperm PS from the inner to the outer leaflet of the plasma membrane is considered to be associated with sperm apoptosis and male infertility. The level of PS externalization in human sperm is used as an indicator for the evaluation of sperm quality. Fast separation of PS-externalized sperm at the molecular level by flow cytometry or magnetic activated cell sorting can effectively improve the quality of sperm and the success rate of assisted reproductive technology. This paper reviews the structure properties, distribution, biological activity and synthesis of PS, as well as its association with male reproduction.
Animals ; Humans ; Infertility, Male ; metabolism ; Male ; Phosphatidylserines ; biosynthesis ; metabolism

Many pathological phenomena of male infertility are related to epigenetic changes in male germ cells. Epigenetic regulation during spermatogenesis plays an important role in mitotic/meiotic divisions and spermiogenesis. The histones have various post-translational modifications on different amino acid residues during spermatogenesis. These modifications are crucial to the precise regulation of spermatogenesis. Moreover, the histone-to-protamine transition will occur during spermiogenesis. Many studies have also found that abnormal changes of histone modifications during spermatogenesis may damage the sperm development, leading to male sterility. This article reviews the changes of histone modifications during spermatogenesis, the regulation of the development of male germ cells, and the relationship between histone abnormalities and male sterility.
Epigenesis, Genetic ; Histones ; metabolism ; Humans ; Infertility, Male ; physiopathology ; Male ; Spermatogenesis

Heat shock protein (HSP) is a group of evolutionarily highly conserved cell chaperone proteins involved in the processes of molecular chaperone, cytoprotection, anti-apoptosis and immunoregulation. Recent studies found that HSP is also involved in spermatogenesis, sperm capacitation and fertilization, which play a significant role in male reproduction. Therefore, further studies on the action mechanisms of HSP in male infertility may offer a new insight into the management of the problem.
Heat-Shock Proteins ; metabolism ; Humans ; Infertility, Male ; metabolism ; Male ; Spermatozoa ; metabolism

Reduced glutathione (GSH) , the most abundant non-protein thiol in mammalian cells, exists extensively in the human body and plays a key role in many biological processes, including the synthesis of proteins and DNA and the transport of amino acids, especially in protecting cells against oxidation. GSH also shows its important clinical value in the treatment of many diseases. It has been reported that GSH also widely exists in the male reproductive system and has a therapeutic role in male infertility. The objective of this review is to summarize the distribution of GSH in the male reproductive system and its therapeutic value for male infertility.
Genitalia, Male ; metabolism ; Glutathione ; metabolism ; therapeutic use ; Humans ; Infertility, Male ; therapy ; Male ; Reproductive Techniques, Assisted

Male reproductive infections are known to shape the immunological homeostasis of the testes, leading to male infertility. However, the specific pathogenesis of these changes remains poorly understood. Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells. Here, we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes (IT-exos) and explore their underlying mechanisms in orchitis. IT-exos were isolated using a uropathogenic Escherichia coli (UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in vitro. We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages (TMs) from normal and UPEC-infected testes, respectively, and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes. Further study of bone marrow derived macrophages (BMDMs) transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype. In addition, the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages; however, IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses. Overall, we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis. Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.
Humans ; Male ; Mice ; Animals ; Orchitis ; Uropathogenic Escherichia coli/metabolism* ; MicroRNAs/metabolism* ; Exosomes/metabolism* ; Macrophages/metabolism* ; Phenotype ; Infertility, Male/metabolism*

OBJECTIVETo study the significance of the change of protamine content in the management of male infertility.

METHODSSperm nuclear proteins extracted from 199 infertile patients were analyzed by polyacrylamide gel-electrophoresis and scanning microdensitometry.

RESULTSForty-two (21%) cases of the total number had normal sperm nuclear proteins and 157 (79%) had aberrant ones, which mainly presented the interruption of HPRR and abnormality of P2 protamine. Thirty patients were selected at random from 157 abnormal cases for clinical treatment. After the treatment, the sperm nuclear proteins were extracted and analyzed and the results demonstrated that 11 cases (36.6%) improved markedly, 5 (16.6%) restored to normal and the other 16 (46.6%) remained unchanged.

CONCLUSIONThere is a reduced level or selective absence or even complete selective absence of protamines in infertile patients. Protamines may act as a parameter for evaluating the treatment effect of infertile males and protamine content can be influenced by a certain or several factors.

Adult ; Electrophoresis, Polyacrylamide Gel ; Humans ; Infertility, Male ; metabolism ; Male ; Oligospermia ; metabolism ; Protamines ; analysis ; Spermatozoa ; chemistry

Metabonomics is an emerging branch of science for the study of endogenous small molecule metabolites in organisms, which plays an important role in evaluatingthediagnosis and treatment of male infertility by exploring the metabolites of body fluids, cells and tissues. With its advantages ofmass information, noninvasiveness, and celerity, metabonomics will be widely applied to clinical researches in the future. This review introducesmetabonomics and its analytical techniques and data processing procedures,its latest application in the studies of the etiology, diagnosis and the treatment of male infertility, and the prospect of its future application in the researches of male reproduction.
Body Fluids ; metabolism ; Humans ; Infertility, Male ; diagnosis ; etiology ; metabolism ; therapy ; Male ; Metabolomics

The incidence of infertility is on the rise worldwide. Statistically, infertility affects approximately 15% of couples and 50% of males, which can be attributed to the decreased sperm quantity and quality and consequently male eugenesis induced by such esoteric factors as quickened pace of life, polluted environment, unhealthy behaviors, and so on. With the establishment and development of the free radical theory, active oxygen-mediated oxidative stress has been found to play a significant role in the pathogenesis of male infertility. This review presents an overview of the esoteric factors responsible for sperm oxidative stress.
Antioxidants ; metabolism ; Humans ; Infertility, Male ; etiology ; metabolism ; Male ; Oxidative Stress ; Reactive Oxygen Species ; metabolism ; Spermatozoa ; metabolism ; pathology

OBJECTIVETo investigate the effects of experimental varicocele on mitochondria calcium and cytochrome C of the epididymal cells in adolescent rats.

METHODSForty male adult Wistar rats were divided into two groups randomly: varicocele group (VG) and sham operation group (SOG) by partial ligation or exposure of the left renal vein. Bilateral epididymides were removed after ten

RESULTSThe content of mitochondria weeks. Mitochondria calcium and cytochrome C levels of the epididymal cells were detected. calcium decreased (P < 0.001 ) while that of cytochrome C increased (P < 0.05) markedly in the experimental group compared with SOG.

CONCLUSIONCalcium dyshomeostasis and mitochondrial damage of the epididymal cells caused by varicocele may play an important role in leading to subfertility.

Animals ; Calcium ; metabolism ; Cytochromes c ; analysis ; Epididymis ; metabolism ; Infertility, Male ; etiology ; Male ; Mitochondria ; metabolism ; Rats ; Rats, Wistar ; Varicocele ; metabolism

Multiple morphological abnormalities of the sperm flagella (MMAF) is a severe form of asthenozoospermia categorized by immotile spermatozoa with abnormal flagella in ejaculate. Whole-exome sequencing (WES) is used to detect pathogenic variants in patients with MMAF. In this study, a novel homozygous frameshift variant (c.6158_6159insT) in dynein axonemal heavy chain 8 (DNAH8) from two infertile brothers with MMAF in a consanguineous Pakistani family was identified by WES. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed DNAH8 mRNA decay in these patients with the DNAH8 mutation. Hematoxylin-eosin staining and transmission electron microscopy revealed highly divergent morphology and ultrastructure of sperm flagella in these patients. Furthermore, an immunofluorescence assay showed the absence of DNAH8 and a reduction in its associated protein DNAH17 in the patients' spermatozoa. Collectively, our study expands the phenotypic spectrum of patients with DNAH8-related MMAF worldwide.
Humans ; Male ; Consanguinity ; Pakistan ; Infertility, Male/metabolism* ; Semen/metabolism* ; Sperm Tail/metabolism* ; Spermatozoa/metabolism* ; Flagella/pathology* ; Mutation