Male meiosis is a complex process whereby spermatocytes undergo cell division to form haploid cells. This review focuses on the role of retinoic acid (RA) in meiosis, as well as several processes regulated by RA before cell entry into meiosis that are critical for proper meiotic entry and completion. Here, we discuss RA metabolism in the testis as well as the roles of stimulated by retinoic acid gene 8 (STRA8) and MEIOSIN, which are responsive to RA and are critical for meiosis. We assert that transcriptional regulation in the spermatogonia is critical for successful meiosis.
Animals ; Cell Differentiation/genetics* ; Humans ; Meiosis/drug effects* ; Spermatogenesis/physiology* ; Tretinoin/metabolism*

The purpose of this study was to determine the diagnostic accuracy of serum inhibin B (INHB) as a predictor of the retrieval outcome of testicular haploid gametes (spermatids and testicular spermatozoa) in nonobstructive azoospermic men. Serum hormone levels, testicular volume, and histological evaluation were performed in 403 Chinese nonobstructive azoospermic men. Testicular haploid gamete was successfully retrieved in 213 of 403 patients (52.85%). The haploid gamete group always had higher INHB levels than the non-haploid gamete group. According to the receiver operating characteristic (ROC) curve analysis, INHB was a good predictor of testicular haploid gamete retrieval outcome in all patients (sensitivity: 77.93% and specificity: 91.58%) and patients with normal follicle-stimulating hormone (FSH; sensitivity: 88.52% and specificity: 70.83%). The area under the ROC curve (AUC) of INHB was similar to that of FSH in all patients or patients with normal FSH. In patients with elevated FSH, INHB was superior to FSH in predicting the presence of haploid gamete (AUC: 0.73 vs 0.55, P < 0.05), with a sensitivity of 60.00% and a specificity of 80.28%. It concluded that serum INHB as an effective marker for spermatogenesis was a significant predictor of testicular haploid gamete retrieval outcomes in nonobstructive azoospermic men. Especially, INHB is superior to FSH in predicting the presence of haploid gamete in the patients with elevated FSH.
Adult ; Azoospermia/blood* ; Follicle Stimulating Hormone/blood* ; Haploidy ; Humans ; Inhibins/blood* ; Male ; Sensitivity and Specificity ; Sperm Retrieval ; Spermatogenesis/physiology*

Nanos2, a member of the Nanos2 gene family, is a specific gene in male germ cells and encodes an evolutionarily conserved RNA binding protein expressed in male primordial germ cells (PGCs) during the embryonic period as well as in the spermatogonial stem cells (SSCs) of the testis. In the embryonic period, Nanos2 promotes the development of male PGCs and inhibits them from meiosis. In the process of spermatogenesis, Nanos2 suppresses the differentiation of SSCs in the testis and maintains the stability of the SSC pool. The knockout of Nanos2 may cause the disappearance of germ cells and sterility in male mice while its overexpression in the testis may lead to accumulation of SSCs in seminiferous tubules. Besides, Nanos2 is involved in the degradation of specific RNAs and possibly associated with some diseases of the male reproductive system. This review focuses on the recent progress in the studies of Nanos2 in the male reproductive system.
Animals ; Cell Differentiation ; Gene Knockout Techniques ; Male ; Meiosis ; Mice ; RNA ; metabolism ; RNA-Binding Proteins ; genetics ; metabolism ; Spermatogenesis ; physiology ; Spermatogonia ; Spermatozoa ; Testis ; cytology

Humans ; Male ; Metaphase/physiology* ; Sex Chromosomes/ultrastructure* ; Spermatocytes/ultrastructure* ; Spermatogenesis ; Testis/ultrastructure*

Objective: To investigate the relationship between the serum anti-Müllerian hormone (AMH) level and semen parameters. METHODS: We collected the data about 726 outpatients at the Male Infertility Clinic of Jinling Hospital from September 2015 to November 2016, including 72 with non-obstructive azoospermia, 123 with oligospermia, and 531 with normal sperm concentration. We obtained the semen volume, total sperm count, sperm concentration, sperm motility, the percentages of progressively motile sperm (PMS) and morphologically normal sperm (MNS), and the levels of serum AMH, inhibin B (INH-B), total testosterone (TT) and follicle - stimulating hormone (FSH) of the patients, analyzed the correlation of the serum AMH level with the other parameters, and compared the AMH level among different groups. RESULTS: The serum AMH level was found to be correlated positively with the total sperm count (r = 0.227, P <0.001), sperm concentration (r = 0.215, P <0.001), sperm motility (r = 0.111, P = 0.003), the percentage of PMS (r = 0.120, P = 0.001), and the levels of INH-B (r = 0.399, P <0.001) and TT (r = 0.184, P = 0.002), negatively with the FSH level (r = －0.283, P <0.001), but insignificantly with age, time of abstinence, semen volume, and the percentage of MNS (P >0.05). There was a statistically significant difference in the serum AMH level among the patients with non-obstructive azoospermia, oligozoospermia, and normal sperm concentration (［6.33 ± 4.26］ vs ［8.26 ± 3.98］ vs ［9.8 ± 5.19］ ng/ml, P <0.001). CONCLUSIONS Serum AMH is a biomarker reflecting the function of Sertoli cells and its level is significantly correlated with sperm concentration and motility, suggesting that AMH may be involved in spermatogenesis and sperm maturation.
Anti-Mullerian Hormone ; blood ; Azoospermia ; blood ; Biomarkers ; blood ; Follicle Stimulating Hormone ; blood ; Humans ; Inhibins ; blood ; Male ; Oligospermia ; blood ; Semen ; Semen Analysis ; Sertoli Cells ; physiology ; Sperm Count ; Sperm Motility ; Spermatogenesis ; Spermatozoa ; Testosterone ; blood

Objective: To investigate the clinical therapeutic effects of Yijingfang, a Chinese medicinal liquid, on asthenospermia. METHODS: We randomly divided 450 asthenospermia patients into a treatment group (n = 300) and a control group (n = 150), the former treated with Yijingfang once half a dose, bid, and the latter with Wuziyanzong Pills (9 g, bid) + L-carnitine oral liquid (10 ml, bid), both for 3 months. Before and at 1, 2, and 3 months after medication, we compared the semen volume, sperm concentration, percentages of progressively motile sperm (PMS) and total motile sperm (TMS), and semen liquefaction time between the two groups of patients. RESULTS: No statistically significant difference was observed in the semen parameters between the treatment and control groups before medication (P >0.05). In comparison with the baseline, the treatment group showed significant differences at 1, 2, and 3 months after medication in sperm concentration (［35.96 ± 8.50］ vs ［49.66 ± 10.91］, ［55.21 ± 11.46］, ［74.90 ± 13.07］ ×10⁶/ml, P <0.01), PMS (［19.72 ± 2.06］ vs ［23.81 ± 2.56］, ［26.12 ± 2.34］, and ［32.17 ± 1.62］ %, P <0.01) and TMS (［28.86 ± 2.70］ vs ［34.17 ± 3.43］, ［36.59 ± 3.36］, and ［47.08 ± 2.97］ %, P <0.01), but not in the semen volume (［3.35 ± 0.99］ vs ［3.15 ± 1.06］, ［3.12 ± 0.90］, and ［3.27 ± 0.78］ ml, P >0.05) or semen liquefaction time (［32.31 ± 8.15］ vs ［31.68 ± 3.14］, ［30.38 ± 3.44］, and ［30.86 ± 2.42］ min, P >0.05); the control group exhibited similar results at the three time points in sperm concentration (［36.85 ± 6.88］ vs ［40.53 ± 8.32］, ［47.51 ± 12.73］, and ［56.14 ± 11.98］ ×10⁶/ml, P <0.01), PMS (［20.26 ± 2.73］ vs ［25.17 ± 2.64］, ［27.23 ± 2.25］, and ［31.89±2.27］ %, P <0.01), and TMS (［30.03 ± 2.67］ vs ［33.89±2.26］, ［37.38±4.79］, and ［40.35±3.06］ %, P <0.01), but not in the semen volume (［3.03 ± 1.09］ vs ［3.16±1.78］, ［3.15±0.96］, and ［3.12±0.65］ ml, P >0.05) or semen liquefaction time (［30.25 ± 5.20］ vs ［29.36±4.25］, ［28.21±3.26］, and ［28.33±3.59］ min, P >0.05). There were statistically significant differences between the treatment and control groups in the increase rates of sperm concentration and TMS after medication (P <0.01) but not in that of PMS (P >0.05). CONCLUSIONS Yijingfang is an effective drug for the treatment of asthenospermia, which can regulate the spermatogenesis, increase the percentage of PMS, and improve the total sperm motility of the patients.
Asthenozoospermia ; drug therapy ; Carnitine ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Male ; Semen ; Sperm Count ; Sperm Motility ; drug effects ; physiology ; Spermatogenesis ; drug effects

Objective: To investigate the effect of aerobic exercise on the spermatogenic function of male rats and screen out differentially expressed proteins related to spermatonesis-regulation by proteomic analysis. METHODS: We randomly divided 24 SD male rats into groups A (non-exercise control), B (exercise), and C (weight-bearing exercise), those in the latter two groups made to swim for 60 minutes a day and those in group C bearing a load 3% of the body weight, both 6 times a week for 9 weeks. At 24 hours after the last exercise, we obtained the sperm count, measured the levels of such serum reproductive hormones as testosterone (T), luteotrophic hormone (LH), follicle-stimulating hormone (FSH), and gonadotrophin-releasing hormone (GnRH), and employed isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis of the testicular tissue. RESULTS: Compared with group A, group C showed significant increases in sperm concentration (［2.12 ± 0.43］ vs ［3.54 ± 0.52］ ×10⁶/ml, P <0.01) and the levels of serum LH (［35.99 ± 2.90］ vs ［38.96 ± 1.34］ IU/L, P <0.01) and T (［19.99 ± 0.25］ vs ［21.36 ± 0.53］ nmol/L, P <0.01), but no statistically significant differences in GnRH (［623.95 ± 41.44］ vs ［641.82 ± 42.78］ ng/L, P >0.05) and FSH (［20.49 ± 2.44］ vs ［22.29 ± 2.31］ IU/L, P >0.05). No significant changes were observed in sperm concentration or reproductive hormone levels in group B as compared with A. Group B exhibited obviously more mature sperm and cell layers in the seminiferous epithelium than group A. A total of 47 differentially expressed proteins were identified, of which 37 were up-regulated and the other 10 down-regulated. In addition, another 5 significantly differentially expressed proteins closely related to reproductive function were identified, including up-regulated Anx A1, GPX3, Rimbp3, and Dpy19l2 and down-regulated CYP17. Enrichment analysis showed that the differentially expressed proteins were mainly involved in extracellular matrix-receptor interaction, protein digestion and absorption, and focal adhesion pathways. CONCLUSIONS Proper-intensity exercise can improve the spermatogenic function of rats. Aerobic exercise promotes spermatogenesis mainly by up-regulating the expressions of the proteins related to the production and differentiation of spermatozoa.
Animals ; Follicle Stimulating Hormone ; blood ; Gonadotropin-Releasing Hormone ; blood ; Luteinizing Hormone ; Male ; Physical Conditioning, Animal ; methods ; Proteomics ; methods ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reproduction ; Resistance Training ; methods ; Sperm Count ; Spermatogenesis ; physiology ; Spermatozoa ; Testis ; Testosterone ; blood

RNA binding proteins (RBPs) regulate the function of cells by interacting with nascent transcripts and therefore are receiving increasing attention from researchers for their roles in tissue development and homeostasis. The polypyrimidine tract binding (PTB) protein family of RBPs are important posttranscriptional regulators of gene expression. Further investigations on the post-transcriptional regulation mechanisms and isoforms of PTB proteins in the spermatogenesis show that PTB protein 1 (Ptbp1) is a predominant isoform in mitotic cells (spermatogonia), while Ptbp2 predominates in meiotic spermatocytes and postmeiotic spermatids and binds to the specific 3' untranslated region (3' UTR) of the phosphoglycerate kinase 2 (Pgk-2) mRNA, which helps to stabilize Pgk-2 mRNA in male mouse germ cells. In case of Ptbp2 inactivation in the testis, the differentiation of germ cells arrests in the stage of round spermatids, with proliferation of multinucleated cells in the seminiferous tubule, increased apoptosis of spermatocytes, atrophy of seminiferous tubules, and lack of elongating spermatids, which consequently affects male fertility. This article presents an overview on the structure of the PTB protein and its role in regulating mammalian spermatogenesis.
Animals ; Atrophy ; Gene Expression Regulation ; physiology ; Heterogeneous-Nuclear Ribonucleoproteins ; metabolism ; physiology ; Homeostasis ; Isoenzymes ; metabolism ; Male ; Mice ; Nerve Tissue Proteins ; metabolism ; physiology ; Phosphoglycerate Kinase ; metabolism ; Polypyrimidine Tract-Binding Protein ; metabolism ; physiology ; RNA, Messenger ; metabolism ; RNA-Binding Proteins ; Seminiferous Tubules ; pathology ; Spermatids ; metabolism ; Spermatocytes ; metabolism ; Spermatogenesis ; physiology ; Spermatogonia ; metabolism ; Testis ; metabolism

The ubiquitin-proteasome system (UPS) is a proteasome system widely present in the human body, which is composed of ubiquitin (Ub), ubiquitin activating enzymes (E1), ubiquitin conjugating enzymes (E2), ubiquitin protein ligases (E3), 26S proteasome, and deubiquitinating enzymes (DUBs) and involved in cell cycle regulation, immune response, signal transduction, DNA repair as well as protein degradation. Sperm DNA is vulnerable to interference or damage in the progression of chromosome association and homologous recombination. Recent studies show that UPS participates in DNA repair in spermatogenesis by modulating DNA repair enzymes via ubiquitination, assisting in the identification of DNA damage sites, raising damage repair-related proteins, initiating the DNA repair pathway, maintaining chromosome stability, and ensuring the normal process of spermatogenesis.
Cell Cycle Proteins ; physiology ; DNA Damage ; DNA Repair ; physiology ; Humans ; Male ; Proteasome Endopeptidase Complex ; physiology ; Signal Transduction ; physiology ; Spermatogenesis ; physiology ; Spermatozoa ; Ubiquitin ; physiology ; Ubiquitin-Conjugating Enzymes ; physiology ; Ubiquitin-Protein Ligases ; physiology ; Ubiquitination

The two-dimensional model of cell culture is an important method in the study of testicular development and spermatogenesis but can not effectively mimic and regulate the testicular microenvironment and the whole process of spermatogenesis due to the lack of relevant cell factors and the disruption of a three-dimensional spatial structure. In the past 20 years, the development and optimization of the in vitro model such as testis organotypic culture and in vivo model such as testis transplantation achieved a transformation from two- to three-dimension. The maintenance and optimization of the testicular niche structure could mimic the testicular microenvironment and cell types including Leydig, Sertoli and germ cells, which showed similar biological behaviors to those in vivo. Besides, the cell suspension or tissue fragment floats in the gas-liquid interface so that the development of somatic and germ cells is well maintained in vitro whilst the feedback linkage between grafted testis tissue and hypothalamus-pituitary of the host rebuilt in the in vitro model provides an endocrinological basis for spermatogenesis, which serves as an effective methodology to better understand the organogenesis and development of the testis as well as testicular function regulation, advancing the concept of treatment of male infertility. Al- though each of the methods may have its limitations, the progress in the processing, freezing, thawing, and transplantation of cells and tissues will surely promote their clinical application and present their value in translational medicine.
Cell Culture Techniques ; Germ Cells ; physiology ; Humans ; Infertility, Male ; therapy ; Male ; Spermatogenesis ; physiology ; Testis ; growth & development