Over-expression of hsa_circ_0000116 in patients with non-obstructive azoospermia and its predictive value in testicular sperm retrieval.

Non-obstructive azoospermia (NOA), identified in approximately 10% of infertile males, is a multifactorial disease whose molecular mechanisms remain unknown. The aim of this study was to identify the role of hsa_circ_0000116 in NOA and illustrate its predictive value in testicular sperm retrieval. The study included 78 individuals, 58 with NOA and 20 with obstructive azoospermia (OA). Serum hormones including testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and estradiol II (E2) were measured. Testicular histopathology was analyzed by at least two pathologists. The expression of hsa_circ_0000116 in testicular tissue samples was detected using real-time PCR, and the circRNA-miRNA-mRNA networks were predicted using bioinformatics analysis. Our study illustrated that the expression of hsa_circ_0000116 was significantly higher in testicular tissue samples of NOA patients than in that of OA patients. Moreover, hsa_circ_0000116 was aberrantly expressed in three different pathological types of NOA: It was significantly up-regulated in patients with Sertoli cell-only syndrome (SCOS) when compared to patients with hypospermatogenesis (HS). In addition, the expression of hsa_circ_0000116 was negatively correlated with Johnsen score, while it was positively correlated with serum FSH level. A multivariate logistic regression model demonstrated that a high level of hsa_circ_0000116 was associated with a low rate of successful testicular sperm retrieval. Bioinformatics analysis and verification experiments showed that one of the most probable potential target miRNA for hsa_circ_0000116 was hsa-miR-449a. Further analysis indicated that hsa_circ_0000116 may be affecting the fertility function through a hsa_circ_0000116-miR-449-autophagy-related competing endogenous RNA (ceRNA) network. We report for the first time that hsa_circ_0000116 may play pivotal roles in regulating spermatogenesis and may also be a potential biomarker for the diagnosis and treatment of NOA, while acting as a predictive tool for the rate of successful testicular sperm retrieval in NOA patients.

Lv MQ ，Zhou L ，Ge P ，Li YX ，Zhang J ，Zhou DX ... -  《-》

Nomogram based on a circular RNA biomarker for predicting the likelihood of successful sperm retrieval via microdissection testicular sperm extraction in patients with idiopathic non-obstructive azoospermia.

Many circular RNAs (circRNAs) are specifically expressed in the testes and seminal plasma of patients with non-obstructive azoospermia (NOA), highlighting them as potential predictors of microdissection testicular sperm extraction (micro-TESE) outcomes. Although research has indicated that circular RNA monoglyceride lipase (circ_MGLL) is highly expressed in the testicular tissues of patients with NOA, the association between circ_MGLL expression and sperm retrieval outcomes (SROs) in patients with idiopathic non-obstructive azoospermia (iNOA) receiving micro-TESE remains unclear. This single-center, retrospective cohort study enrolled 114 patients with iNOA who underwent micro-TESE at Northwest Women's and Children's Hospital from January 2017 to November 2021. A logistic regression model was used to examine associations between SRO and circ_MGLL expression in testicular tissues, the results of which were used in conjunction with previous findings to establish a nomogram. The predictive performance of the circ_MGLL-based nomogram was evaluated via calibration curves, receiver operating characteristic curves, and decision curve analysis (DCA) using an internal validation method. The generalized additive model indicated that the probability of successful SRO for micro-TESE decreased as circ_MGLL expression increased in testicular tissues. Across the entire cohort, univariate logistic regression analysis revealed that circ_MGLL expression was inversely associated with SRO in patients with NOA. This trend did not change after stratification according to age, body mass index, testicular volume, follicle-stimulating hormone (FSH) level, luteinizing hormone (LH) level, testosterone (T) level, or pathological type (or after adjusting for these confounders) (odds ratio <1, P < 0.001). A nomogram was then generated by integrating circ_MGLL, pathological types, and FSH, LH, and T levels. The circ_MGLL-based predictive model achieved satisfactory discrimination, with an area under the curve of 0.857, and the calibration curves demonstrated impressive agreement. The DCA indicated that the net clinical benefit of the circ_MGLL-based predictive model was greater than that of circ_MGLL alone. circ_MGLL is significantly associated with the SRO of micro-TESE in patients with iNOA. The circ_MGLL-based nomogram developed in the current study can predict successful SRO with high accuracy.

Shi S ，Wang T ，Wang L ，Wang M ... -  《Frontiers in Endocrinology》

Conventional testicular sperm extraction (TESE) and non-obstructive azoospermia: is there still a chance in the era of microdissection TESE? Results from a single non-academic community hospital.

Spermatozoa can be retrieved in non-obstructive azoospermia (NOA) patients despite the absence of ejaculated spermatozoa in their semen because of the presence of isolated foci with active spermatogenesis. Conventional testicular sperm extraction (c-TESE) in patients with NOA has been partially replaced by micro-TESE. It is still under debate the problem regarding the higher costs related to micro-TESE when compared with c-TESE. In this study, we evaluated sperm retrieval rate (SRR) of c-TESE in naive NOA patients. Sixty-three NOA patients were referred to our centre for a c-TESE. For every subject, we collected demographic data, cause of infertility, time to first infertility diagnosis, serum levels of LH, FSH, total testosterone and prolactin. A statistical analysis was conducted to correlate all the clinical variables, the histology and the Johnsen score with the SRR. Sixty-three consecutive NOA patients with a mean age of 37.3 years were included. The positive SRR was 47.6%. No statistical differences were observed between positive vs. negative SRR regarding mean FSH (17.12 vs. 19.03 mUI/mL; p = 0.72), and LH (9.72 vs. 6.92 mUI/mL; p = 0.39) values. Interestingly, we found a statistically significant difference in terms of time to first infertility diagnosis (+SRR vs. -SRR; 44.5 vs. 57 months; p = 0.02) and regarding to age (+SSR vs. -SRR; 40.1 vs. 35.3; p = 0.04). There was a statistically significant decrease in SRRs with the decline in testicular histopathology from hypospermatogenesis to maturation arrest, and SCO. The mean Johnsen score was 5.9 with a mean percentage of Johnsen score ≥8 tubules equal to 19%. The overall pregnancy rate was 26.6%. In our prospective cohort of patients successful SRR with c-TESE was 47.6%. Lower costs and high reproducibility of this technique still support this procedure as an actual reliable option in NOA patients for sperm retrieval.

Saccà A ，Pastore AL ，Roscigno M ，Naspro R ，Pellucchi F ，Fuschi A ，Maruccia S ，Territo A ，Pisano F ，Zanga L ，Capitanio E ，Carbone A ，Fusi F ，Chinaglia D ，Da Pozzo LF ... -  《-》

CircRNA expression profile and functional analysis in testicular tissue of patients with non-obstructive azoospermia.

Ge P ，Zhang J ，Zhou L ，Lv MQ ，Li YX ，Wang J ，Zhou DX ... -  《Reproductive Biology and Endocrinology》

Ultrasonographic caput epididymis diameter is reduced in non-obstructive azoospermia compared with normozoospermia but is not predictive for successful sperm retrieval after TESE.

Pezzella A ，Barbonetti A ，D'Andrea S ，Necozione S ，Micillo A ，Di Gregorio A ，Francavilla F ，Francavilla S ... -  《-》