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*

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

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

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

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

OBJECTIVETo study the impact of the chloride channel dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) on the cytoskeleton of Sertoli cells in the mouse.

METHODSTM4 Sertoli cells were cultured and treated with CFTR(inh)-172 at the concentrations of 1, 5, 10 and 20 μmol/L for 48 hours. Then the cytotoxicity of CFT(inh)-172 was assessed by CCK-8 assay, the expressions of F-actin and Ac-tub in the TM4 Sertoli cells detected by immunofluorescence assay, and those of N-cadherin, vimentin and vinculin determined by qPCR.

RESULTSCFTR(inh)-172 produced cytotoxicity to the TM4 Sertoli cells at the concentration of 20 μmol/L. The expressions of F-actin and Ac-tub were decreased gradually in the TM4 Sertoli cells with the prolonging of treatment time and increasing concentration of CFTR(inh)-172 (P < 0.05). The results of qPCR showed that different concentrations of CFTR(inh)-172 worked no significant influence on the mRNA expressions of N-cadherin, vimentin and vinculin in the Sertoli cells.

CONCLUSIONThe CFTR chloride channel plays an important role in maintaining the normal cytoskeleton of Sertoli cells. The reduced function and expression of the CFTR chloride channel may affect the function of Sertoli cells and consequently spermatogenesis of the testis.

Actins ; metabolism ; Animals ; Benzoates ; pharmacology ; Chloride Channels ; physiology ; Cystic Fibrosis Transmembrane Conductance Regulator ; antagonists & inhibitors ; Cytoskeleton ; drug effects ; Male ; Mice ; Sertoli Cells ; drug effects ; metabolism ; Spermatogenesis ; Thiazolidines ; pharmacology ; Time Factors

Spermiogenesis is a complex process of differentiation and morphologic alteration, in which sperm acrosome formation is an important stage. Acrosome is an essential component of the sperm head, which develops in four distinct phases: Golgi, cap, acro- somal, and maturation, each supported by precise and orderly regulation of various genes. The regulatory genes which act on Golgi ap- paratus include GOPC, Hrb, SPATA16, PICK1, and CK2α', those involved in the cap phase are Fads2, syntaxin 2, Kdm3a, and UBR7, and participating in acrosomal and maturation phases are KIFC1, Rnf19a, and DPY19L2. The abnormalities of these genes may affect male fertility by influencing the connection of the nuclear dense lamina and acroplaxome with the nuclear membrane and then the fusion and transportation of vesicles. This review focuses on the genes involved in different phases of acrosome formation.
Acrosome ; physiology ; Animals ; Golgi Apparatus ; Male ; Mice ; Sperm Head ; physiology ; Spermatids ; growth & development ; Spermatogenesis ; genetics ; Spermatozoa ; growth & development