MicroR-1199-5p targeting SRD5A2 promotes the biological behavior and EMT of hypospadias cells.

Hypospadias, an oft-occurring penis anomaly, ranks among neonatal's foremost birth defects. The SRD5A2 can affect male reproductive system development and is abnormally expressed in its epithelial cells. This study exploration aimed at understanding the role of SRD5A2 in the development of hypospadias from a molecular perspective. SRD5A2 levels in hypospadias primary cells were analyzed by Western blot, while targeted interaction with miR-1199-5p was ascertained by dual-luciferase gene reporter assay. In vitro biological experiments were used to confirm the biological function of SRD5A2 in hypospadias. SRD5A2 expression was significantly upregulated, and miR-1199-5p expression was significantly downregulated in hypospadias primary cells. Intervention of SRD5A2 expression can affect cell proliferation, migration, invasion, EMT, and the expression of cell cycle-related proteins. Additionally, we found that SRD5A2 is regulated by upstream miR-1199-5p and can enhance the effect of SRD5A2 on hypospadias cells. Conclusions Silencing SRD5A2 promotes cell proliferation, invasion, and migration blocks the cell cycle at the G1 phase, and simultaneously promotes EMT, cell cycle, and cell proliferation-related protein expression. The biological function of SRD5A2 in hypospadias cells is regulated by miR-1199-5p. SRD5A2 may be an effective therapeutic target for hypospadias.

Clinical characteristics and surgical treatment of children with 45, X/46, XY differences of sex development.

OBJECTIVE: This study retrospectively analyzes the clinical data of 18 children with 45,X/46,XY differences of sex development (DSD), summarizes their clinical features and explores gonadal and Müllerian duct remnants surgical treatment methods. METHODS: The clinical data of 18 children with karyotype 45,X/46,XY diagnosed in the Department of Urology of Hunan Children's Hospital from March 2011 to October 2021 were collected. All children underwent HCG stimulation testing, laparoscopic exploration, urethroscopy and bilateral gonadal biopsy. After DSD multidisciplinary team (MDT) meeting, some children underwent gonadectomy and genitalia reconstructive surgeries. RESULTS: The median age at first diagnosis was 1 year and 4 months (range: 10 months ∼ 16 years and 3 months). 5 children presented with female gender; they all maintained their gender assignment. The external masculinisation score (EMS) of patients raised as female was 1 (0∼3) [median (range)]. 13 children presented with male gender, 10 maintained a male gender, 3 were assigned a neutral gender. The EMS of the children raised as male was 5 (2-8) [median (range)], the EMS of the children raised as neutral gender was 4 (3.5-9.5) [median (range)]. The HCG stimulation test was positive in 11 cases, partially positive in 2 case, and negative in 5 cases. There was no relationship between the percentage of chimerism (45X ratio) and the appearance and severity of genital abnormalities. (t=-1.08, P=0.298). There was 1 case of complete gonadal dysgenesis (CGD), 10 cases of mixed gonadal dysgenesis (MGD), 5 cases of partial gonadal dysgenesis (PGD), 1 case of bilateral normal testes and 1 case of ovotesticular DSD (split-lateral type). No gonadal specimen showed germ cell tumor changes. Five cases selected to maintain the female gender, among which 3 cases underwent bilateral gonadectomy and genitalia reconstructive surgeries. Among the 10 children who chose to maintain the male gender, unilateral streak gonadectomy was performed in 4 (57.1%) with MGD, unilateral dysgenetic orchiectomy in 1 (25%) with PGD, and right ovariectomy in 1 with OTDSD. Nine of them underwent genitalia reconstructive surgeries. Four of them preserved their uterus and vagina did not have any complications during the follow-up period. CONCLUSION: Hypospadias combined with cryptorchidism and residual Müllerian duct structures is the most common phenotype of children with 45, X/46, XY DSD. Mixed gonadal dysgenesis (MGD) is the most common gonadal type. Gender assignment should be carefully selected after a thorough evaluation, while genitalia reconstructive surgery can be considered in selected patients. In children who choose the male gender, the Müllerian duct can be preserved.

Risk-Factor Analysis and Prediction-Model Construction of Urethral Stricture after Hypospadias Surgery in Children: A Single-Centre Retrospective Study.

OBJECTIVE: This study aimed to explore the incidence of postoperative urethral stricture in children after hypospadias surgery, analyse its risk factors, and construct a prediction model. METHODS: We retrospectively analysed the clinical data of 402 children with hypospadias surgery in Hunan Children's Hospital from January 2022 to January 2023. To explore the risk factors of urethral stricture after hypospadias surgery in children, the incidence of postoperative urethral stricture in children was statistically analysed, and univariate and multivariate logistic regression analyses were adopted. A prediction model was established, and the prediction efficiency of the model was examined using a receiver operating characteristic curve. RESULTS: The incidence of postoperative urethral stricture in children after hypospadias surgery was 9.20% (37/402). On this basis, the children were divided into stricture group (SG, n = 37) and normal group (NG, n = 365). Both groups had overt differences in disease classification, urinary tract infection, indwelling-catheter time, and surgical methods (p < 0.05). Logistic regression analysis showed that urinary tract infection, surgical methods, and long indwelling-catheter time were the risk factors (p < 0.001). The prediction model constructed based on the above results had certain prediction efficiency. CONCLUSIONS: More attention should be paid to children with urinary tract infection, high-risk surgery, and long indwelling-catheter time after hypospadias surgery. Our prediction model can serve as an effective reference for evaluating the occurrence of postoperative urethral stricture.

Risk factors for postoperative complications following one-stage proximal hypospadias repair involving the disconnection of the urethral plate: a retrospective study.

BACKGROUND: Children with hypospadias are at risk of serious physical and mental health problems, including abnormal urination, sexual dysfunction, and infertility. The sole available treatment is the surgical restoration of genital appearance and function. Proximal hypospadias (PH) correction is more challenging and carries a higher risk of complications than does distal hypospadias correction, with a higher likelihood of postoperative complications requiring additional surgery, resulting in considerable economic and psychological strain for families. Herein, we aimed to identify factors associated with complications following one-stage PH repair with urethral plate disconnection. METHODS: We retrospectively analyzed data from 236 children who underwent PH repair at our center between December 2020 and December 2022. We collected information on age, surgical procedure, length of the reconstructed urethra (LRU), glans width (GW), ventral curvature, surgical approach, preoperative androgen use, suture type, presence of prostatic utricle, body mass index, season of surgery, anesthesia type, low birth weight, preterm birth, follow-up period, and complications. Surgical complications included urethral fistulas, urethral diverticula, anastomotic strictures, urethral strictures, glans dehiscence, and penile curvature recurrences. The study population was divided into complication and no-complication groups, and univariate and multivariate analyses were conducted. RESULTS: Of the 236 patients with PH who had a median follow-up of 10.0 (8.0, 14.0) months, 79 were included (33.5%) in the complication group and 157 were included (66.5%) in the no-complication group. In the univariate analysis, age (P < 0.001), LRU (P < 0.001), degree of penile curvature (P = 0.049), and PH with prostatic utricle (P = 0.014) were significantly associated with complications after PH repair. In the multivariate logistic regression analysis, LRU (P<0.001, odds ratio [OR] = 3.396, 95% confidence interval [CI]: 2.229-5.174) and GW (P = 0.004, OR = 0.755, 95%CI: 0.625-0.912) were independent factors influencing postoperative complications. The optimal LRU threshold was 4.45 cm (area under the curve, 0.833; sensitivity, 0.873; specificity, 0.873; P<0.001, OR = 3.396, 95% CI: 2.229-5.174). CONCLUSIONS: LRU and GW are independent factors affecting PH complications. An LRU of < 4.45 cm and an increased GW can reduce the risk of complications.