Mitochondria-related miR-574 reduces sperm ATP by targeting ND5 in aging males.

Couples are delaying childbearing in recent decades. While women experience a notable decrease in oocyte production in their late thirties, the effect of advanced paternal age on reproduction is incompletely understood. Herein, we observed that numerous miRNAs, including miR-574, increased in the sperm of aging males, as indicated by high-throughput sequencing. We demonstrated that miR-574 was upregulated in the sperm of two aging mouse models and was related to inferior sperm motility as an adverse predictor. Moreover, we proved that miR-574 suppressed mitochondrial function and reduced cellular ATP production in GC2 cells. Mechanistically, we demonstrated that miR-574 regulated mitochondrial function by directly targeting mt-ND5. Our study revealed an important role of miR-574 in sperm function in aging males and provided a fresh view to comprehend the aging process in sperm.

Spermatogenesis improved by suppressing the high level of endogenous gonadotropins in idiopathic non-obstructive azoospermia: a case control pilot study.

BACKGROUND: Elevated plasma gonadotropins were associated with desensitization of Sertoli and Leydig cells in the male testis. Testis spermatogenesis ability would be improved via inhibiting high endogenous gonadotropin in patients with severe oligozoospermia. Whether it would be beneficial for non-obstructive azoospermia (NOA) patients was still unclear. METHODS: Goserelin, a gonadotropin releasing hormone agonist (GnRHα) was used to suppress endogenous gonadotropin levels (gonadotropin reset) in the NOA patients, improving the sensitization of the Sertoli and Leydig cells. Then human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) were injected to stimulate them to ameliorate the ability of testicular spermatogenesis. The main outcome measure was the existence of spermatozoa in the semen or by testicular sperm extraction (TESE). Elevation of inhibin B and/or ameliorative expression pattern of ZO-1 was the secondary objective. RESULTS: A total of 35 NOA men who failed to retrieve sperm via TESE were enrolled. Among these, 10 patients without treatment were selected as control group and secondary TESE was performed 6 months later. Of the 25 treated men, inhibin B was elevated in 11 patients in the first 4 weeks (Response group), while only 5 patients had constant increase in the following 20 weeks (Response group 2). Of the 5 men, 2 men acquired sperm (Response group 2B), while 3 failed (Response group 2A). Immunofluorescence of mouse vasa homologue (MVH) and ZO-1 showed that both positive MVH signals and ZO-1 expression were significantly increased in the Response group 2, but only Response group 2B showed ameliorative ZO-1 distribution. CONCLUSIONS: Gonadotropin reset, a new therapeutic protocol with GnRHα, was able to improve the ability of testicular spermatogenesis in the NOA patients through restoring the sensitivity of Sertoli and Leydig cells, which were reflected by elevated inhibin B and ameliorative ZO-1 expression and distribution. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02544191 .

Grape seed proanthocyanidin extract attenuates varicocele­induced testicular oxidative injury in rats by activating the Nrf2­antioxidant system.

The present study investigated whether grape seed proanthocyanidin extract (GSPE) can attenuate varicocele­induced testicular oxidative injury through the nuclear factor (erythroid­derived 2)­like 2 (Nrf2) antioxidant pathway. A varicocele model in rats was established by partial ligation of the left renal vein. Following 4 weeks of GSPE administration, the decreased sperm count and motility and other pathological changes caused by varicocele were significantly alleviated, as indicated by the results of computer­assisted sperm analysis and hematoxylin and eosin staining. In addition, the decreased antioxidant enzyme (superoxide dismutase and glutathione peroxidase) activity and elevated oxidative stress level were partially reversed by administration of GSPE. Furthermore, the apoptotic level of the testis induced by varicocele was decreased by the GSPE treatment, according to terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Additionally, the expression of apoptosis­related proteins, including B­cell lymphoma 2 (Bcl­2), Bcl­2­like protein 4 and cleaved caspase­3, were also affected by GSPE. GSPE activated Nrf2, which is a key antioxidative transcription factor, with elevation of the downstream factor hemeoxygenase­1. These findings suggest that GSPE can ameliorate abnormal spermatogenesis and testicular injury in varicocele rats, potentially due to its antioxidative activity and ability to activate the Nrf2 pathway.

Ectopic Cushing's syndrome due to retroperitoneal ACTH-producing paragangliomas.

Extra-adrenal pheochromocytomas, or paragangliomas, are rare tumours that derive from extra-adrenal chromaffin cells. Cushing's syndrome (CS) caused by paragangliomas is extremely rare. We report a 53-year-old man with hypertension, diabetes, and symptoms of hypokalemia. Computer tomography (CT) revealed two retroperitoneal masses and bilateral adrenal hyperplasia. Together with the laboratory examinations, ectopic CS caused by multiple paragangliomas was highly suspected. The patient underwent resections of retroperitoneal tumours, left kidney, and left adrenal; postoperative histopathology confirmed two paragangliomas that were both positively stained for adrenocorticotropic hormone (ACTH). He got clinical and biochemical recoveries without any recurrent evidence at the nine-month followup.

Clinical characteristics and pathology of thyroid-like follicular carcinoma of the kidney: Report of 3 cases and a literature review.

Thyroid-like follicular carcinoma (TLFC) of the kidney is an extremely rare type of renal tumor, which has not been classified under a known subtype of renal cell carcinoma. It is histologically similar to the primary thyroid follicular carcinoma; however, the characteristics lack thyroid immunohistochemical markers. The aim of the present study was to illustrate the clinical characteristics of 3 new cases along with a review of the literature. The patients were compared with regards to gender, age, location and size of the tumor, imageology, morphology, immunohistochemistry and prognosis. According to the limited data, TLFC occurs mainly in young women and its clinical manifestations have no difference with other renal tumors. Its imageological features resemble a large spectrum of benign and malignant renal and extra-renal conditions, which should be eliminated in the diagnostic process. Confirmed diagnosis depends on the examination of pathology and immunohistochemistry. Surgical ablation is the preferred therapeutic method. Currently, TLFC has a relatively good prognosis; however, this conclusion requires further cases and long-term follow-ups. Improving the understanding of TLFC can help avoid misdiagnosis and prevent inappropriate treatment.