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Becoming a phenotypic male is ultimately determined by androgen-induced masculinization. Disorders of fetal masculinization, resulting in hypospadias or cryptorchidism, are common, but their cause remains unclear. Together with the adult-onset disorders low sperm count and testicular cancer, they can constitute a testicular dysgenesis syndrome (TDS). Although masculinization is well studied, no unifying concept explains normal male reproductive development and its abnormalities, including TDS. We exposed rat fetuses to either anti-androgens or androgens and showed that masculinization of all reproductive tract tissues was programmed by androgen action during a common fetal programming window. This preceded morphological differentiation, when androgen action was, surprisingly, unnecessary. Only within the programming window did blocking androgen action induce hypospadias and cryptorchidism and altered penile length in male rats, all of which correlated with anogenital distance (AGD). Androgen-driven masculinization of females was also confined to the same programming window. This work has identified in rats a common programming window in which androgen action is essential for normal reproductive tract masculinization and has highlighted that measuring AGD in neonatal humans could provide a noninvasive method to predict neonatal and adult reproductive disorders. Based on the timings in rats, we believe the programming window in humans is likely to be 8-14 weeks of gestation.

Background Cryptorchidism is one of the most common reproductive abnormalities in rams, which seriously harms the reproductive capacity of rams and causes significant economic losses to the sheep industry. However, there are few studies elucidating its hereditary predisposition in sheep. Results In the present study, the transcriptome and proteome of the cryptic (CT) and contralateral (CLT) testis from four unilaterally cryptorchid rams, and the normal testis (NT) from four healthy rams were analyzed using RNA-seq and TMT-based proteomics, respectively. A total of 10,357, 10,175, and 132 differentially expressed genes (DEGs) were identified between CT vs. CLT, CT vs. NT, and CLT vs. NT. Venn diagram showed that 9744 DEGs (5499 up-regulated and 4245 down-regulated) shared in CT vs. CLT and CT vs. NT. Functional enrichment analysis revealed that 5499 up-regulated DEGs were mainly involved in regulation of programmed cell death and metabolic process, while 4245 down-regulated DEGs were closely related to reproductive process, such as spermatogenesis, sexual reproduction, reproduction and male gamete generation. Furthermore, 325 overlapped genes (114 up-regulated and 211 down-regulated) between DEGs and DAPs that shared the same regulatory status were identified by combining transcriptomics and proteomics. Ten genes, including AKAP4 , AKAP3 , FSIP2 , HSPA1L , HSPA4L , TUBB , TXNRD2 , CDC42 , PGK1 and HSPA1A , were identified as candidate key genes related to unilateral cryptorchidism. Conclusion Our results revealed that both gene and protein expression in the cryptic testis of unilateral cryptorchid rams is massively altered. Bioinformatics analysis unveiled several candidate genes and signaling pathways potentially involved in unilateral cryptorchidism. These findings provide new insights into the molecular mechanism underlying spermatogenesis failure caused by cryptorchidism.

Cryptorchidism is one of the most common congenital malformations in the paediatric genitourinary tract. Data analysis of cryptorchidism‐related datasets in the GEO database and gene sequencing results from our institution, along with bioinformatic analysis of the merged mitochondrial gene datasets, revealed that COX5B is differentially expressed in the testes of children with cryptorchidism. Its encoded protein has attracted our attention as a key component of the mitochondrial respiratory chain complex IV. This study aims to explore the COX5B gene expression changes and related mitochondrial issues in cryptorchid rats. For this purpose, we established a cryptorchid rat model by surgery and used molecular biology and biochemistry techniques to detect and analyse the expression level of the COX5B gene and mitochondrial function indexes. The results indicated a significant decrease in COX5B gene expression in the affected testis of cryptorchid rats. The knockdown of COX5B expression in TM3 cells could be observed as the aggravation of cellular senescence, which led to the reduction of proliferation, as well as accompanied by the obvious disorders of mitochondrial function, including the increase of ROS and the decrease of ATP, in which MMP was significantly reduced. This suggests that the COX5B gene may play an important role in cryptorchid testis‐induced reproductive system damage and may be a new target for small molecule‐targeted therapy.

Cryptorchidism, a prevalent congenital defect in pigs, raises animal welfare and economic concerns in the breeding industry. This study utilized a genome-wide transcriptome analysis, examining samples from the pituitary gland, cremaster muscle and testis of one-week-old piglets. In the cremaster muscle of cryptorchid piglets,1225 genes exhibited significant differential expression (log2FoldChange = |2.0|, p-adjusted value ≤ 0.01). Downregulated genes were linked to biological processes like muscle tissue development and actin cytoskeleton organization. Pathway analysis further revealed the suppression of metabolic pathways including ‘Oxidative phosphorylation’, ‘TCA cycle’ and ‘Motor Proteins’. Notably, several genes integral to the motor protein pathway were significantly downregulated. Additionally, crucial genes in the noncanonical Wnt signalling pathway that regulates tissue morphogenesis and repair during the embryonic stage, were also suppressed. Our results indicate that a disruption in the normal testicular descent is accompanied by the suppression of major genes in the motor protein pathway, potentially hampering the presumed role of the cremaster muscle in testicular descent. However, we propose this to be a consequence of the down regulation of key genes in the noncanonical Wnt signalling pathway. Based on our findings, future research might be able to uncover causal mutations related to the expression of these genes.

To compare the impact of the scrotal vs inguinal orchidopexy approach on the testicular function of infants with cryptorchidism, a randomized controlled trial was conducted involving boys who were 6-12 months old at surgery and were diagnosed with clinically palpable, inguinal undescended testis. Between June 2021 and December 2021, these boys at Fujian Maternity and Child Health Hospital (Fuzhou, China) and Fujian Children's Hospital (Fuzhou, China) were enrolled. Block randomization with a 1:1 allocation ratio was employed. The primary outcome was testicular function assessed by testicular volume, serum testosterone, anti-Müllerian hormone (AMH), and inhibin B (InhB) levels. Secondary outcomes included operative time, amount of intraoperative bleeding, and postoperative complications. Among 577 screened patients, 100 (17.3%) were considered eligible and enrolled in the study. Of the 100 children who completed the 1-year follow-up, 50 underwent scrotal orchidopexy and 50 underwent inguinal orchidopexy. The testicular volume, serum testosterone, AMH, and InhB levels in both groups increased markedly after surgery (all P < 0.05), but there were no apparent differences between groups at 6 months and 12 months after operation (all P > 0.05). No differences between the scrotal and inguinal groups were noted regarding the operative time (P = 0.987) and amount of intraoperative bleeding (P = 0.746). The overall complication rate (2.0%) of the scrotal group was slightly lower than that of the inguinal group (8.0%), although this difference was not statistically significant (P > 0.05). Both scrotal and inguinal orchiopexy exerted protective effects on testicular function in children with cryptorchidism, with similar operative status and postoperative complications. Scrotal orchiopexy is an effective alternative to inguinal orchiopexy in children with cryptorchidism.

Background Traditional open orchiopexy remains the standard treatment for palpable undescended testicles (UDT). However, laparoscopic orchiopexy has recently gained attention as an alternative approach. Aim and objectives This study aimed to compare the outcomes of laparoscopic versus open orchiopexy for high-inguinal undescended testes. Subjects and methods A prospective randomized comparative study was conducted, involving 208 children with high inguinal undescended testes. The patients were divided into two groups: group A (104 patients) underwent laparoscopic orchiopexy and group B (104 patients) underwent open orchiopexy. Results There was a significant difference in the final testicular position between the two groups. The follow-up after 1 year showed that 100% of patients in group A had a lower testicular position, compared to 72.6% in group B. Laparoscopic orchiopexy demonstrated better outcomes in terms of achieving a lower testicular position. Conclusion Both Laparoscopic and Open Orchiopexy are safe and effective for the treatment of high inguinal undescended testes. However, Laparoscopic Orchiopexy was superior to Open Orchiopexy because it was associated with better outcomes with regard to the final testicular position at the bottom of the scrotum or at a lower level below the mid-scrotal point.

Congenital cryptorchidism is a well-established risk factor of testicular malignancies. However, there is still remarkable variability in the measures of associations between of these two clinical entities. The current meta-analysis investigates the up-to-date risk of testicular cancer in adults with a history of surgically corrected congenital cryptorchidism until adolescence. The meta-analysis was conducted with strict criteria for the identification of the congenital cryptorchidism cases that underwent surgery before adulthood. The study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search of the PubMed and the Scopus databases was conducted, using a defined strategy, from inception to February 2023. Two independent authors screened the literature and extracted the data, using inclusion and exclusion criteria. Of the 2176 articles identified, 93 articles were fully retrieved, and 6 articles met all the inclusion criteria. The Newcastle–Ottawa scale was applied for the studies’ quality assessment. The random-effects model in RevMan 5.4 program was used for the meta-analysis. Three case–control studies and three cohort studies were selected. They included 371,681 patients and 1786 incidents of testicular cancer. The pooled odds ratio (OR) was 3.99 (95% confidence intervals (CI): 2.80–5.71). The heterogeneity was moderate and estimated at 51% with the I -squared statistic. A forest plot and a funnel plot were produced to evaluate the ORs and the probable publication bias, respectively. The mean Newcastle–Ottawa score was 8/9 for all the included reports.   Conclusion : This systematic review and meta-analysis verifies, with an updated estimate, the increased risk of testicular cancer in adults with an orchidopexy history. New evidence on the maldescent laterality supports that the cancer risk remains increased and for the contralateral, unaffected testicle, although to a lesser extent. The orchidopexy in the first year of life prevents the testicular damage and decreases the overall cancer risk. What is Known: • Congenital cryptorchidism is the commonest genitourinary abnormality and a risk factor for testicular cancer. • The most recent meta-analysis reporting this association was in 2013. What is New: • After reviewing literature until February 2023, the association of congenital cryptorchidism with testicular cancer risk in adulthood was verified: odds ratio=3.99 [2.80–5.71], 95% CI. • The meta-analysis highlights the protective role of early orchidopexy and the controversial data about maldescent and testicular cancer laterality.