Deciphering the Molecular Characteristics of Human Idiopathic Nonobstructive Azoospermia from the Perspective of Germ Cells.

Nonobstructive azoospermia (NOA) is one of the most important causes of male infertility, accounting for 10-15% of infertile men worldwide. Among these, more than 70% of cases are idiopathic NOA (iNOA), whose pathogenesis and molecular basis remain unknown. This work profiles 3696 human testicular single-cell transcriptomes from 17 iNOA patients, which are classified into four classes with different arrest periods and variable cell proportions based on the gene expression patterns and pathological features. Genes related to the cell cycle, energy production, and gamete generation show obvious abnormalities in iNOA germ cells. This work identifies several candidate causal genes for iNOA, including CD164, LELP1, and TEX38, which are significantly downregulated in iNOA germ cells. Notably, CD164 knockdown promotes apoptosis in spermatogonia. Cellular communications between spermatogonial stem cells and Sertoli cells are disturbed in iNOA patients. Moreover, BOD1L2, C1orf194, and KRTCAP2 are found to indicate testicular spermatogenic capacity in a variety of testicular diseases, such as Y-chromosome microdeletions and Klinefelter syndrome. In general, this study analyzes the pathogenesis of iNOA from the perspective of germ cell development, transcription factor (TF) regulatory networks, as well as germ cell and somatic cell interactions, which provides new ideas for clinical diagnosis.

The role of Chito-oligosaccharide in regulating ovarian germ stem cells function and restoring ovarian function in chemotherapy mice.

In recent years, the discovery of ovarian germ stem cells (OGSCs) has provided a new research direction for the treatment of female infertility. The ovarian microenvironment affects the proliferation and differentiation of OGSCs, and immune cells and related cytokines are important components of the microenvironment. However, whether improving the ovarian microenvironment can regulate the proliferation of OGSCs and remodel ovarian function has not been reported. In this study, we chelated chito-oligosaccharide (COS) with fluorescein isothiocyanate (FITC) to track the distribution of COS in the body. COS was given to mice through the best route of administration, and the changes in ovarian and immune function were detected using assays of organ index, follicle counting, serum estrogen (E2) and anti-Mullerian hormone (AMH) levels, and the expression of IL-2 and TNF-α in the ovaries. We found that COS significantly increased the organ index of the ovary and immune organs, reduced the rate of follicular atresia, increased the levels of E2 and AMH hormones, and increased the protein expression of IL-2 and TNF-α in the ovary. Then, COS and OGSCs were co-cultured to observe the combination of COS and OGSCs, and measure the survival rate of OGSCs. With increasing time, the fluorescence intensity of cells gradually increased, and the cytokines IL-2 and TNF-α significantly promoted the proliferation of OGSCs. In conclusion, COS could significantly improve the ovarian and immune function of chemotherapy model mice, and improve the survival rate of OGSCs, which provided a preliminary blueprint for further exploring the mechanism of COS in protecting ovarian function.

Altered regional homogeneity in patients with diabetic vitreous hemorrhage.

BACKGROUND: Diabetic vitreous hemorrhage (DVH) is a common complication of diabetes. While the diagnostic methods nowadays only concentrate on the eye injury in DVH patients, whether DVH leads to abnormalities of other visual systems, including the eye, the visual cortex, and other brain regions, remains unknown. AIM: To explore the potential changes of brain activity in DVH using regional homogeneity (ReHo) and their relationships with clinical features. METHODS: Thirty-one DVH patients and 31 matched healthy controls (HCs) were recruited. All subjects were examined by resting-state functional magnetic resonance imaging. The neural homogeneity in the brain region was estimated by ReHo method. Pearson correlation analysis was used to evaluate the relationships between average ReHo values and clinical manifestations in DVH patients. RESULTS: Compared with HCs, the ReHo values in the bilateral cerebellar posterior lobes, right superior (RS)/middle occipital gyrus (MOG), and bilateral superior frontal gyrus were significantly increased. In contrast, in the right insula, bilateral medial frontal gyri, and right middle frontal gyrus, the ReHo values were significantly decreased. Furthermore, we found that best-corrected visual acuity of the contralateral eye in patients with DVH presented a positive correlation with the mean ReHo value of the RS/MOG. We also found that depression score of the DVH group presented a negative correlation with the mean ReHo values of the right insula, bilateral medial frontal gyrus, and right middle frontal gyrus. CONCLUSION: We found that DVH may cause dysfunction in multiple brain areas, which may benefit the exploration of pathologic mechanisms in DVH patients.

Resting-state functional magnetic resonance imaging (fMRI) and functional connectivity density mapping in patients with corneal ulcer.

PURPOSE: To investigate alternations in spontaneous brain activities reflected by functional connectivity density (FCD) in patients with corneal ulcer (CU) using resting-state functional connectivity (rsFC). METHODS: We recruited 24 patients with CU (12 males, 12 females), and 24 healthy controls (HCs; 12 males, 12 females) matched for age, gender and education status. Functional magnetic resonance imaging examinations were performed on all subjects in a resting state and the following parameters determined: rsFC, long-range FCD (longFCD) and short-range FCD (IFCD). Receiver operating characteristic (ROC) curves were then used to differentiate patients with CU from HCs. RESULTS: Compared with HCs, CU patients showed significantly reduced rsFC values in the right cerebellum posterior lobe gyrus, right middle frontal gyrus/inferior frontal gyrus/superior frontal gyrus and left inferior parietal lobule/precuneus. Significantly reduced longFCD values were found in the right hippocampus/inferior temporal gyrus and the left inferior temporal gyrus. Moreover, compared with HCs, IFCD values were significantly reduced in the left inferior temporal gyrus/middle temporal gyrus, left limbic lobe/medial frontal gyrus, and left precuneus/limbic lobe, but were significantly increased in the right insula/superior temporal gyrus, left superior temporal gyrus/inferior frontal gyrus/insula, right superior temporal gyrus/postcentral gyrus, and left precentral gyrus. CONCLUSIONS: Patients with CU exhibited alterations in spontaneous brain activities in several brain areas. These novel findings may help to reveal the neuropathological mechanisms underlying CU.This study provides a direction for further exploration of underlying neural mechanisms of CU and facilitate the clinical diagnosis and treatment of CU.

Abnormalities of interhemispheric functional connectivity in individuals with acute eye pain: a resting-state fMRI study.

AIM: To study the changes of the resting state functional connectivity (rsFC) between acute eye pain (EP) subjects and healthy controls (HCs) in the two hemispheres by using voxel-mirrored homotopic connectivity (VMHC) method. METHODS: Totally 20 patients with EP and 20 HCs were enrolled, sex, age, and education were matched, and all subjects were examined by functional magnetic resonance imaging (fMRI) scans at resting-state. The changes of rsFC between the hemispheres were evaluated by the VMHC method according to Gaussian random field (GRF) theory. In order to identify the VMHC, as biomarkers for distinguishing EP and from HC, the receiver operating characteristic curves (ROC) had been analyzed. The relationships were evaluated with Pearson correlation analysis between the mean VMHC signal values and clinical features in these patients. RESULTS: By comparing with health subjects, the significant decreased VMHC values was observed in lingual/calcarine (Brodmann area, BA 30), precentral/postcentral gyrus (PreCG/PosCG; BA 4) and medial frontal gyrus (MFG; BA 8) (false discovery rate corrected <0.01) in the acute EP individuals. The accuracy of area under curve was excellent indicated by the ROC curve analysis of each brain regions. CONCLUSION: Our study demonstrates preliminary evidence of disrupted interhemispheric rsFC in acute EP in sensorimotor and limbic system and somatosensory cortex, which might give some useful information for understanding the neurological mechanisms in acute EP individuals.

Research advances in the regulation of the putative ovarian germline stem cell niche on female germline stem cells.

Stem cells are ideal seeding cells, which have the potential for self-renewal and multiple differentiation, and they play a fundamental role in maintaining homeostasis and regenerating and repairing tissue. The discovery of female germline stem cells (FGSCs) brings much hope for the postnatal renewal of oocytes and solving some female infertility problems. Ovarian function declines with increasing female age. Moreover, ovarian germline stem cell niche-aging could be the main cause of ovarian senescence, which ultimately leads to decreased follicle generation, declining female fertility, and age-related diseases, such as osteoporosis and ovarian cancer. The ovarian germline stem cell niche is the surrounding microenvironment in which FGSCs live, and it helps control the biological characteristics of FGSCs in many ways, such as nutritional supply and immunological cytokine secretion. This paper reviews the knowledge about the ovarian germline stem cell niche and its probable regulatory mechanisms on FGSCs, which provides valuable scientific information and scope for the prevention and treatment of ovarian senescence. Abbreviations: BMP: bone morphogenetic protein; Dpp: decapentaplegic; FGSC: female germline stem cell; IL, interleukin; OGSC: ovarian germline stem cells; ROS: reactive oxygen species; TGF, transforming growth factor; TNF, tumor necrosis factor.