Widening of narrow urethral plates with lateral skin in TIP hypospadias repair: single center series.

BACKGROUND: To compare the outcomes of hypospadias repair using tubularized incised plate (TIP) urethroplasty and modified TIP with lateral skin to widen the urethral plate (WTIP). MATERIALS AND METHODS: Data were obtained from pre-pubertal boys who underwent primary hypospadias repair between May 2018 and July 2023. The cases were divided into two groups; one group underwent TIP with urethral plate ≥ 6 mm width and the other group with urethral plate width < 6 mm underwent WTIP. WTIP urethroplasty was performed by widening incisions on the outer margins of the urethral plate to incorporate penile and glandular skin lateral to the urethral plate to facilitate tubularization. Complication rates and urinary functions were compared. RESULTS: A total of 157 patients were enrolled in this study. Eighty-eight cases with narrow urethral plate were subjected to WTIP urethroplasty, and the rest were subjected to TIP urethroplasty. The preoperative glans width in WTIP group was less than that in TIP group (P < 0.001), and 44.3% had midshaft meatus in WTIP group compared to 17.4% in TIP group (P < 0.001). However, the incidences of postoperative complications (17.6% vs. 21.6%, P = 0.550) were not statistically different between the TIP and WTIP groups. In addition, both groups did not differ significantly in postoperative uroflowmetry assessment. CONCLUSIONS: The described technique helps to create an adequately caliber aesthetic neomeatus and facilitates tubularization, especially in hypospadias with a narrow urethral plate. Our data suggest that augmentation of a narrow urethral plate with WTIP has a similar surgical outcome to that of the TIP procedure in patients with a wide urethral plate.

Postoperative care in hypospadias. Common practices and evidence available. / Cuidados postoperatorios en el hipospadias. Prácticas habituales y evidencia disponible.

INTRODUCTION: There are many alternatives available regarding postoperative care in hypospadias surgery. The objective of this study was to assess the current care situation in our environment and to review the evidence available for pediatric surgeons who conduct this procedure. MATERIALS AND METHODS: A survey regarding the main aspects of hypospadias postoperative care was created and distributed to pediatric surgeons. In addition, the evidence currently published in this field was reviewed. RESULTS: A total of 46 replies were achieved. 100% of the surgeons leave in place a probe or stent, and more than 80% remove it after 5 or 7 days. 87.8% of the respondents use a double diaper, but only 65.2% discharge patients early in the postoperative period. 60.9% prescribe antibiotic prophylaxis for as long as the probe remains in place, and 34.8% use full-dose antibiotic therapy. DISCUSSION: There was a general consensus regarding urethroplasty guiding and the use of compression dressings among the pediatric surgeons surveyed. However, more discrepancies were found in the use of antibiotic therapy and early discharge. The currently available evidence and international practice suggest using a probe with double diaper and early discharge, with postoperative antibiotics being limited. In the absence of clear evidence for a specific care type, the patient's experience could be used to choose the best postoperative protocol on an individual basis.

INTRODUCCION: Existen numerosas alternativas en lo que respecta a los cuidados postoperatorios en la cirugía de hipospadias. El objetivo de este estudio es evaluar la situación actual de estos cuidados en nuestro medio y revisar la evidencia existente al respecto para cirujanos pediátricos que realizan este tipo de intervenciones. MATERIAL Y METODOS: Hemos elaborado y distribuido una encuesta que recoge los principales puntos en el cuidado postoperatorio del hipospadias dirigida a cirujanos pediátricos. Se ha realizado revisión de la evidencia actual publicada al respecto en la especialidad. RESULTADOS: Hemos obtenido un total de 46 respuestas. El 100% de los cirujanos dejan algún tipo de sonda o stent y más del 80% están de acuerdo en retirarlo tras 5 o 7 días. El 87,8% de los encuestados utiliza el doble pañal, pero solo el 65,2% da alta precoz en el postoperatorio. Un 60,9% pauta profilaxis antibiótica mientras dure el sondaje y un 34,8% antibioterapia a dosis plenas. DISCUSION: Existe consenso general respecto a la tutorización de la uretroplastia y el uso de apósito compresivo entre los cirujanos pediátricos encuestados. Se detectan más discrepancias en el uso de antibioterapia y el alta precoz. La evidencia actual y la práctica a nivel internacional apunta hacia el uso de la sonda a doble pañal con alta precoz y la limitación del uso de antibióticos postoperatorios. En ausencia de clara evidencia que favorezca un tipo de cuidado u otro, la experiencia del paciente podría ser utilizada para elegir el mejor protocolo postoperatorio individualizado.

The potentiating effect of intravenous dexamethasone upon preemptive pudendal block analgesia for hypospadias surgery in children managed with Snodgrass technique: a randomized controlled study : Dexamethasone for pain management in children.

INTRODUCTION: Evidence regarding the potentiating effects of intravenous dexamethasone on peripheral regional anesthesia in children is sparse. The objective of the current study was to investigate the potentiating effect of intravenous dexamethasone upon pudendal block during surgical correction of hypospadias using Snodgrass technique. METHODS: The study consisted of a monocentric, randomized controlled, double-blinded study. Patients were randomized to receive either intravenous dexamethasone 0.15 mg.kg- 1 (D group) or a control solution (C group). Both groups received standardized anesthesia including a preemptive pudendal block performed after the induction of anesthesia. The primary outcome was the proportion of patients needing rescue analgesia. Secondary outcomes were other pain outcomes over the first 24 postoperative hours. RESULTS: Overall, 70 patients were included in the study. Age were 24 [24; 36] and 26 [24; 38] months in the D and C groups, respectively (p = 0.4). Durations of surgery were similar in both groups (60 [30; 60], p = 1). The proportion of patients requiring rescue analgesia was decreased in the D group (23% versus 49%, in D and C groups respectively, p = 0.02). The first administration of rescue analgesia was significantly delayed in the D group. Postoperative pain was improved in the D group between 6 and 24 h after surgery. Opioid requirements and the incidence of vomiting did not significantly differ between groups. CONCLUSION: Associating intravenous dexamethasone (0.15 mg.kg- 1) to pudendal block during hypospadias surgery improves pain control over the first postoperative day. Further studies are needed in order to confirm these results. GOV IDENTIFIER: NCT03902249. A. WHAT IS ALREADY KNOWN: dexamethasone has been found to potentiate analgesia obtained with regional anesthesia in children. B. WHAT THIS ARTICLE ADDS: intravenous dexamethasone was found to improve analgesia with a preemptive pudendal block during hypospadias surgery. C. IMPLICATIONS FOR TRANSLATION: results of this study indicate that intravenous dexamethasone could be used as an adjunct to pudendal block.

Identification and analysis of MSC-Exo-derived LncRNAs related to the regulation of EMT in hypospadias.

OBJECTIVE: This study aims to screen the differentially expressed long non-coding RNAs (DELncRNAs) related to the regulation of epithelial-mesenchymal transition (EMT) in hypospadias in mesenchymal stem cell-derived exosomes (MSC-Exons) and explore the potential mechanism of these lncRNAs for the EMT in hypospadias. METHODS: In this study, the microarray data related to MSC-Exos and hypospadias were downloaded from Gene Expression Omnibus (GEO). Besides, the lncRNAs highly expressed in MSC-Exos and the differentially expressed mRNAs and lncRNAs in children with hypospadias were screened, respectively. In addition, the lncRNAs enriched in MSC-Exos and differentially expressed lncRNAs in hypospadias were intersected to obtain the final DElncRNAs. Moreover, the co-expression interaction pairs of differentially expressed lncRNAs and mRNAs were analyzed to construct a Competing Endogenous RNA (ceRNA) network. Finally, the candidate lncRNAs in exosomes were subjected to in vitro cell function verification. RESULTS: In this study, a total of 4 lncRNAs were obtained from the microarray data analysis. Further, a ceRNA regulatory network of MSC-Exo-derived lncRNAs related to the regulation of EMT in hypospadias was constructed, including 4 lncRNAs, 2 mRNAs, and 6 miRNAs. The cell function verification results indicated that the exosomes secreted by MSCs may transport HLA complex group 18 (HCG18) into target cells, which promoted the proliferation, migration, and EMT of these cells. CONCLUSION: MSC-Exo-derived lncRNA HCG18 can enter target cells, and it may be involved in the regulation of EMT in hypospadias through the ceRNA network.

Cuidados postoperatorios en el hipospadias. Prácticas habituales y evidencia disponible / Postoperative care in hypospadias: common practices and evidence available

Introducción: Existen numerosas alternativas en lo que respecta alos cuidados postoperatorios en la cirugía de hipospadias. El objetivo deeste estudio es evaluar la situación actual de estos cuidados en nuestromedio y revisar la evidencia existente al respecto para cirujanos pediátricos que realizan este tipo de intervenciones. Material y métodos: Hemos elaborado y distribuido una encuestaque recoge los principales puntos en el cuidado postoperatorio del hipospadias dirigida a cirujanos pediátricos. Se ha realizado revisión dela evidencia actual publicada al respecto en la especialidad.Resultados: Hemos obtenido un total de 46 respuestas. El 100% delos cirujanos dejan algún tipo de sonda o stent y más del 80% están deacuerdo en retirarlo tras 5 o 7 días. El 87,8% de los encuestados utilizael doble pañal, pero solo el 65,2% da alta precoz en el postoperatorio.Un 60,9% pauta profilaxis antibiótica mientras dure el sondaje y un34,8% antibioterapia a dosis plenas. Discusión: Existe consenso general respecto a la tutorización de lauretroplastia y el uso de apósito compresivo entre los cirujanos pediátricos encuestados. Se detectan más discrepancias en el uso de antibioterapia y el alta precoz. La evidencia actual y la práctica a nivel internacional apunta hacia el uso de la sonda a doble pañal con alta precozy la limitación del uso de antibióticos postoperatorios. En ausencia declara evidencia que favorezca un tipo de cuidado u otro, la experienciadel paciente podría ser utilizada para elegir el mejor protocolo postoperatorio individualizado.(AU)

Introduction: There are many alternatives available regarding postoperative care in hypospadias surgery. The objective of this study wasto assess the current care situation in our environment and to review theevidence available for pediatric surgeons who conduct this procedure. Materials and methods. A survey regarding the main aspects ofhypospadias postoperative care was created and distributed to pediatricsurgeons. In addition, the evidence currently published in this field wasreviewed. Results: A total of 46 replies were achieved. 100% of the surgeonsleave in place a probe or stent, and more than 80% remove it after 5 or7 days. 87.8% of the respondents use a double diaper, but only 65.2%discharge patients early in the postoperative period. 60.9% prescribeantibiotic prophylaxis for as long as the probe remains in place, and34.8% use full-dose antibiotic therapy. Discussion: There was a general consensus regarding urethroplastyguiding and the use of compression dressings among the pediatric surgeons surveyed. However, more discrepancies were found in the use ofantibiotic therapy and early discharge. The currently available evidenceand international practice suggest using a probe with double diaperand early discharge, with postoperative antibiotics being limited. Inthe absence of clear evidence for a specific care type, the patient’sexperience could be used to choose the best postoperative protocol onan individual basis.(AU)

A case of mild partial androgen insensitivity syndrome in a juvenile boy.

Androgen insensitivity syndrome (AIS) is a rare disorder with X-linked recessive inheritance in 46 XY patients. The clinical manifestations vary between patients, especially regarding external genitalia development. Herein, the case of AIS in a 13-year-old male, who was born with hypospadias and presented to the hospital with gynaecomastia that had developed from 8 years of age, is reported. No micropenis, cryptorchidism or bifid scrotum were found. Testis volume was 12 ml on both sides. His testosterone and luteinizing hormone levels were normal compared with sex- and age-adjusted reference range. His bone age was approximately 13 years according to Greulich-Pyle assessment. Sequence analysis of the androgen receptor (AR) gene revealed a mutation (c.2041A>G) in exon 4, a novel mutation site in the AR gene. Prediction analysis suggested this to be a disease-causing variant. A milder clinical presentation and normal hormone levels in cases of partial AIS might differ from the usually reported signs and symptoms. A diagnosis of AIS should not be ignored in teenage patients who present with gynaecomastia and hypospadias, but normal hormone levels.

[Value of the human chorionic gonadotropin stimulation test in the diagnosis of disorder of sexual development in children]. / äººç»’æ¯›è†œä¿ƒæ€§è ºæ¿€ç´ æ¿€å‘è¯•éªŒåœ¨æ€§å‘è‚²å¼‚å¸¸å„¿ç«¥ä¸­çš„è¯Šæ–­ä½œç”¨è¯„ä¼°.

OBJECTIVES: To investigate the value of the human chorionic gonadotropin (hCG) stimulation test in the diagnosis of disorder of sexual development (DSD) in children. METHODS: A retrospective analysis was conducted on 132 children with DSD. According to the karyotype, they were divided into three groups: 46,XX group (n=10), 46,XY group (n=87), and sex chromosome abnormality group (n=35). The above groups were compared in terms of sex hormone levels before and after hCG stimulation test, and the morphological manifestation of the impact of testicular tissue on the results of the hCG stimulation test was analyzed. RESULTS: There was no significant difference in the multiple increase of testosterone after stimulation among the three groups (P>0.05). In the 46,XY group, the children with 5α-reductase type 2 deficiency had a testosterone-to-dihydrotestosterone ratio higher than that of the 46,XY DSD children with other causes. Morphological analysis showed that DSD children with testicular tissue demonstrated a significantly higher multiple increase in testosterone after stimulation compared to children without testicular tissue (P<0.05). CONCLUSIONS: The hCG stimulation test has an important value in assessing the presence and function of testicular interstitial cells in children with different types of DSD, and it is recommended to perform the hCG stimulation test for DSD children with unclear gonadal type.

Modified versus Classical Tubularised Incised Plate Urethroplasty in Hypospadias: A Comparative Study.

BACKGROUND: Hypospadias is a wide-world congenital malformation that accounts for 1 of 300 live male births. Many procedures were considered for its management. As the tubularised incised plate (TIP) urethroplasty, the most prevalent technique, caused many complications, several modifications were applied to the original operation to improve the outcomes and alleviate complications. The aim of this study was to compare the outcome of the ordinary TIP urethroplasty with the technique modified without dissection of the glans penis. MATERIALS AND METHODS: A total of 82 patients with a mean age of 18.8 (±14.8) months, were randomly assigned to undergo TIP with either complete glans wings mobilisation (Group A, n = 42 patients) or without glans dissection (Group B, n = 40 patients). To evaluate the effect of modified TIP urethroplasty without glanular dissection for treatment of distal hypospadias in contrast to classical TIP repair. RESULTS: Both techniques showed similar outcomes regarding functional repair, with good to excellent results between 88% and 90% after 6 months of follow-up. Most confronted post-operative complications were wound infection, oedema, urethrocutaneous fistulas and meatal stenosis. Less frequently haematoma, post-operative bleeding and glans dehiscence were encountered. The differences in complication rates between the two studied groups were statistically insignificant except for oedema (P = 0.04), and need for urethral dilatation (P = 0.002) that were more prevalent among patients who were treated with classic TIP repair with complete glans wings mobilisation. CONCLUSION: From our point of view, it seems that TIP without glanular dissection technique does not outweigh TIP with complete glans wings mobilisation regarding functional outcomes and post-operative complications.

The application of the modified Snodgrass technique in hypospadias surgery.

OBJECTIVE: We aimed to explore the effectiveness of the modified tubularized incised plate urethroplasty (Snodgrass Technique) in hypospadias surgery. PATIENTS AND METHODS: A study was conducted on 50 pediatric patients with hypospadias treated in our hospital from May 2020 to May 2023. The patients were divided into two groups based on the condition of their urethral plate; 22 patients were included in the study group and 28 patients were included in the control group. The control group underwent the traditional Snodgrass technique, while the study group received the modified Snodgrass technique. The two groups were compared in terms of treatment efficacy, preoperative and postoperative 6-month Hypospadias Objective Scoring Evaluation (HOSE) scores, surgical data, and postoperative complications. RESULTS: The operation time for the study group was longer than that of the control group, and the intraoperative blood loss was less, but the differences were not statistically significant (p > 0.05). The success rate of surgery in the study group was 95.45% (21/22), compared to 71.43% (20/28) in the control group, showing a statistically significant difference (p < 0.05). The maximum urinary flow rate at 3 and 6 months postoperatively was significantly higher in the study group than in the control group (p < 0.05). The time to maximum flow (TQmax) and post-void residual (PVR) at 3 and 6 months postoperatively were significantly lower in the study group (p < 0.05). A total of 3 patients in the cohort developed urethral fistulas, all between 0.10 cm x 0.10 cm and 0.15 cm x 0.15 cm in size. By instructing the patients to apply pressure to the fistula during urination, all fistulas closed between 3 and 6 months postoperatively. The incidence of postoperative complications was 4.55% in the study group and 28.57% in the control group, a difference that was statistically significant (p < 0.05). CONCLUSIONS: The modified Snodgrass technique shows significant therapeutic effectiveness in hypospadias surgery, substantially increasing the success rate and reducing postoperative complications in pediatric patients, making it suitable for widespread application.

Primary hypospadias repair outcomes: results from a retrospective cohort of 292 children.

PURPOSE: Hypospadias surgery is challenging. Numerous techniques have been described with variable complication rates. The main objectives of our study were to evaluate the urethroplasty complication rate of primary hypospadias repair and to identify risk factors for complications. METHODS: We retrospectively evaluated the outcomes of all patients who underwent primary hypospadias repair in our department between January 2012 and December 2020. Demographic, anatomical, operative, and postoperative data were reported. Univariate and multivariate logistic regression analyses were performed to identify variables associated with complications. Statistical significance was set at p < 0.05. RESULTS: Of 292 patients, 203 (69.5%) had distal hypospadias, 63 (21.6%) had mid-penile hypospadias, and 26 (8.9%) had proximal hypospadias. The mean age at the time of surgery was 22.8 months. Seventy-eight patients (26.7%) had urethroplasty complications. The rate of complications was higher for proximal hypospadias (57.7%), onlay island flap (44.4%), and Koyanagi (75%) procedures. The mean follow-up duration was 29 months. Two predictors of complications were identified by multivariate analysis: catheterization duration and urethroplasty technique. The reoperation rate was 30.5%. CONCLUSION: Urethroplasty complications frequently occur after primary hypospadias repair. The complication rate was higher in proximal hypospadias. Catheterization duration and surgical technique were significant predictors of complications. A longer and more standardized follow-up is needed for a better assessment of hypospadias repair outcomes.

Adult Hypospadias Outcomes for the Pediatric Urologist.

PURPOSE OF REVIEW: This review article will examine the current literature on hypospadias-related complications in adult patients. RECENT FINDINGS: In this article, we will review the most recent studies evaluating hypospadias-related stricture disease, erectile function, fertility, and psychosexual outcomes in adult men with history of hypospadias repair in childhood. Managing hypospadias-related complications in adult patients is challenging to reconstructive urologists due to the compounded complexity of innate tissue deficiency and history of prior surgical repairs. In this review, we explore overall functional outcomes of adults with history of hypospadias repair as well as repair strategies of hypospadias-related urethral stricture disease. We will review erectile function, fertility and psychosexual outcomes as well as potential complications, which often do not surface until late adolescence and adulthood. Although it is challenging to characterize and quantify hypospadias-related complications, further longitudinal study is needed to better care for this complex patient population.

Rab25 is involved in hypospadias via the ß1 integrin/EGFR pathway.

BACKGROUND: Hypospadias is a common congenital abnormality of the penile. Abnormal regulation of critical genes involved in urethral development leads to hypospadias. We used the Rab25-/- mice and foreskin fibroblasts transfected with lentivirus in vitro and in vivo to investigate the role of Rab25 in hypospadias. METHODS: The expression levels of various molecules in tissue samples and foreskin fibroblasts were confirmed using molecular biology methods (western blotting, PCR, immunohistochemistry, etc.). A scanning electron microscope (SEM) was used to visualize the external morphology of genital tubercles (GTs) of gestation day (GD) 18.5 male wild-type (WT) and Rab25-/- mice. RESULTS: An expanded distal cleft and V-shaped urethral opening were observed in GD 18.5 Rab25-/- mice. We demonstrated that Rab25 mediated hypospadias through the ß1 integrin/EGFR pathway. In addition, silencing Rab25 inhibited cell proliferation and migration and promoted apoptosis in the foreskin fibroblasts; Ki-67- and TUNEL-positive cells were mainly concentrated near the urethral seam. CONCLUSION: These findings suggest that Rab25 plays an essential role in hypospadias by activation of ß1 integrin/EGFR pathway, and Rab25 is a critical mediator of urethral seam formation in GD18.5 male fetal mice.

The median effective concentration of ropivacaine for ultrasound-guided caudal block in children: a dose-finding study.

PURPOSE: To determine the 50% minimum effective concentration (MEC50) and the 95% effective concentration (MEC95) of ropivacaine for ultrasound-guided caudal block during hypospadias repair surgery of pediatric patients. METHODS: Children were enrolled with the American Society of Anesthesiologists (ASA) physical status I-II undergoing elective hypospadias repair surgery. Children were grouped into two age groups: toddlerhood (1-3 years old) and preschool (3-6 years old). We measured The MEC50 using Dixon's up-and-down method. The first children received the caudal block with 1.0 mL/kg of 0.15% ropivacaine. We determined each subsequent patient's concentration based on the previous patient's response and adjusted the concentration in intervals of 0.015%. Meanwhile, the probit regression analysis obtains 95% effective concentration (MEC95). In addition, we recorded the general condition, adverse events, and postoperative pain of each child. RESULTS: 46 children undergoing elective hypospadias repair surgery were included in this study, 22 in the toddlerhood group and 24 in the preschool group. Of the total number of patients, the caudal block was successful in 25 (54%) and failed in 21 (46%). The MEC50 of 1 ml/kg ropivacaine was 0.102% (95% CI 0.099%, 0.138%) in the toddlerhood group and 0.129% (95% CI 0.124%, 0.138%) in the preschool group. The MEC95 of 1 ml/kg ropivacaine was 0.148% (95% CI 0.131%, 0.149%) in the toddlerhood group and 0.162% (95% CI 0.134%, 0.164%) in the preschool group. Our results showed that ropivacaine concentration was statistically different between preschool children and toddlers (P < 0.001). None of the adverse events occurred. CONCLUSIONS: This study showed that children in the preschool group required higher concentrations of ropivacaine than children in the toddler group during ultrasound-guided sacral block combined with non-intubated general anesthesia. At the same time, this method of anesthesia is safe and effective for children undergoing surgery for hypospadias.

Advantages of Urethroplasty Terminating at the Corona for Severe Hypospadias: Complications, Uroflowmetry, and Esthetics.

PURPOSE: Mid-shaft/proximal (msp) and penoscrotal/scrotal/perineal (pssp) hypospadias treated by urethroplasty (UP) terminating at the corona (UPC) or UP terminating at the tip of the glans (UPG) were compared. METHODS: UP performed at a single institute (n = 234) between 2003 and 2020 were grouped as: msp-UPC (n = 23), msp-UPG (n = 75), pssp-UPC (n = 81), and pssp-UPG (n = 55) to compare data obtained from medical records for post-UP complications (PUC; urethral stenosis, urethrocutaneous fistula, diverticulum formation, and bleeding; n = 234), post-UP uroflowmetry (PUF; average flow rate (Qave), maximum flow rate (Qmax), voiding time (VT), voided volume (VV) and urine flow curves) in 57 UP patients [msp-UPC (n = 5), msp-UPG (n = 12), pssp-UPC (n = 32), pssp-UPG (n = 8)] and 9 controls, and post-UPC esthetics (EST; n = 104). P < 0.05 was considered significant. RESULTS: Mean ages at UP (years) were: msp-UPC (3.1 ± 3.0), msp-UPG (3.3 ± 1.4), pssp-UPC (4.6 ± 2.4), and pssp-UPG (3.4 ± 1.4); p < 0.0001 by ANOVA test. Overall, there were significantly more PUC in pssp-UPG compared with pssp-UPC except for bleeding. Ages at PUF assessment were similar. Mean Qave (mL/s) for pssp-UPG (4.0 ± 1.0) was significantly less than pssp-UPC (5.9 ± 2.5; p < 0.05) and both were significantly less than controls (6.9 ± 1.8; p < 0.05, p < 0.01, respectively). Mean Qmax (mL/s) for pssp-UPC (11.4 ± 4.8) was significantly better than pssp-UPG (7.8 ± 2.3; p < 0.05) and for controls (14.9 ± 4.4) was significantly better than pssp-UPG (7.8 ± 2.3; p < 0.01). All VT (seconds) were similar to controls; all urine flow curves were normal. For EST in UPC (n = 104), 3 cases requested meatal advancement. CONCLUSIONS: UPC may be a valid option for treating pssp hypospadias because of significant differences in PUC/PUF and minimal EST issues compared with UPG. LEVEL OF EVIDENCE: Prognosis Study Level-Ⅱ.

Genistein prevents the production of hypospadias induced by Di-(2-ethylhexyl) phthalate through androgen signaling and antioxidant response in rats.

Environmental estrogen exposure has increased dramatically over the past 50 years. In particular, prenatal exposure to estrogen causes many congenital diseases, among which reproductive system development disorders are extremely serious. In this study, the molecular mechanism of hypospadias and the therapeutic effect of genistein (GEN) were investigated through in vivo models prepared by Di-(2-ethylhexyl) phthalate (DEHP) exposure between 12 and 19 days of gestation. With increased DEHP concentrations, the incidence of hypospadias increased gradually. DEHP inhibited the key enzymes involved in steroid synthesis, resulting in decreasing testosterone synthesis. At the same time, DEHP increased reactive oxygen species (ROS) and produced inflammatory factors via NADPH oxidase-1 (NOX1) and NADPH oxidase-4 (NOX4) pathways. It also inhibited Steroid 5 α Reductase 2 (Srd5α2) and decreased dihydrotestosterone (DHT) synthesis. Additionally, DEHP inhibited the androgen receptor (AR), resulting in reduced DHT binding to the AR that ultimately retarded the development of the external reproductive system. GEN, a phytoestrogen, competes with DEHP for binding to estrogen receptor ß (ERß). This competition, along with GEN's antiestrogen and antioxidant properties, could potentially reverse impairments. The findings of this study provide valuable insights into the role of phytoestrogens in alleviating environmental estrogen-induced congenital diseases.

Maternal Diabetes and Risk of Hypospadias: A Systemic Review and Meta-Analysis.

INTRODUCTION: This study aimed to investigate the association between maternal diabetes and the risk of hypospadias in male infants, as the relationship between them remains uncertain. METHODS: To comprehensively evaluate the association between pregestational diabetes mellitus and gestational diabetes mellitus with hypospadias, we conducted a systematic review and meta-analysis. A thorough literature search was conducted, encompassing relevant publications published prior to January 2023. Crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Our meta-analysis comprised a total of 13 studies, 11 of which investigated the relationship between pregestational diabetes mellitus and hypospadias, while 9 studies explored the association between gestational diabetes mellitus and hypospadias. Notably, these investigations yielded compelling evidence of significant positive associations between pregestational diabetes mellitus and hypospadias (OR = 1.51, 95% CI = 1.13-2.03), as well as between gestational diabetes mellitus and hypospadias (OR = 1.18, 95% CI = 1.04-1.35). CONCLUSION: Our findings suggest that both pregestational diabetes mellitus and gestational diabetes mellitus are associated with an increased risk of hypospadias in offspring. Further investigations are needed to explore the optimal range of blood glucose during pregnancy that minimizes the risk of congenital malformation in the fetus, as well as to develop more effective measures for glycemic control in pregnant women.