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Background: In 2001, Skakkebæk et al. proposed that certain male reproductive disorders might be grouped into a syndrome called testicular dysgenesis syndrome (TDS), as they all appear to be associated with disruption of the embryonic and foetal programming of gonadal development. TDS may be manifested in early life by the presence of genital malformations (hypospadias and cryptorchidism) and in adult life as disorders represented by low sperm counts and testicular cancer. Changes in androgen hormones during the foetal development, in addition to resulting in TDS, can also cause permanent changes in anopenile anogenital distance (AGDap) and anoscrotal anogenital distance (AGDas). Aims: The objective of this study was to determine whether there is a relationship between late manifestations of TDS and reduced anogenital/anoscrotal distance. Materials and Methods: The present study is a systematic review and meta-analysis. The research included papers from 2001 to 2020, comprising a total of 737 articles, and 13 articles were selected. Results: Linear regression analysis was performed to evaluate the relationship between the two anogenital distance measures, which showed a significant positive association (P = 0.039). A meta-analysis was also performed and compared AGDap and AGDas between control and case groups, with cases defined as men with any late TDS manifestation. These data showed a significant reduction in AGDas in the affected population (P = 0.04), but no differences in the AGDap measure (P = 0.59). Conclusion: Our study confirmed a significant relationship between reduced AGDas and late manifestations of TDS, providing further support to the association between prenatal androgen deficiency and late-onset reproductive disorders. [ABSTRACT FROM AUTHOR]

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The TP53 R337H mutation is associated with increased incidence of pediatric adrenocortical tumor (ACT). The different environmental conditions where R337H carriers live have not been systematically analyzed. Here, the R337H frequencies, ACT incidences, and R337H penetrance for ACT were calculated using the 2006 cohort with 4165 R337H carriers living in Paraná state (PR) subregions. The effectiveness of a second surveillance for R337H probands selected from 42,438 tested newborns in PR (2016 cohort) was tested to detect early stage I tumor among educated families without periodical exams. Estimation of R337H frequencies and ACT incidence in Santa Catarina state (SC) used data from 50,115 tested newborns without surveillance, ACT cases from a SC hospital, and a public cancer registry. R337H carrier frequencies in the population were 0.245% (SC) and 0.306% (PR), and 87% and 95% in ACTs, respectively. The ACT incidence was calculated as ~6.4/million children younger than 10 years per year in PR (95% CI: 5.28; 7.65) and 4.15/million in SC (CI 95%: 2.95; 5.67). The ACT penetrance in PR for probands followed from birth to 12 years was 3.9%. R337H carriers living in an agricultural subregion (C1) had a lower risk of developing pediatric ACT than those living in industrial and large urban subregion (relative risk = 2.4). One small ACT (21g) without recurrence (1/112) was detected by the parents in the 2016 cohort. ACT incidence follows R337H frequency in each population, but remarkably environmental factors modify these rates. [ABSTRACT FROM AUTHOR]

Background: In 2001, Skakkebæk et al . proposed that certain male reproductive disorders might be grouped into a syndrome called testicular dysgenesis syndrome (TDS), as they all appear to be associated with disruption of the embryonic and foetal programming of gonadal development. TDS may be manifested in early life by the presence of genital malformations (hypospadias and cryptorchidism) and in adult life as disorders represented by low sperm counts and testicular cancer. Changes in androgen hormones during the foetal development, in addition to resulting in TDS, can also cause permanent changes in anopenile anogenital distance (AGDap) and anoscrotal anogenital distance (AGDas)., Aims: The objective of this study was to determine whether there is a relationship between late manifestations of TDS and reduced anogenital/anoscrotal distance., Materials and Methods: The present study is a systematic review and meta-analysis. The research included papers from 2001 to 2020, comprising a total of 737 articles, and 13 articles were selected., Results: Linear regression analysis was performed to evaluate the relationship between the two anogenital distance measures, which showed a significant positive association ( P = 0.039). A meta-analysis was also performed and compared AGDap and AGDas between control and case groups, with cases defined as men with any late TDS manifestation. These data showed a significant reduction in AGDas in the affected population ( P = 0.04), but no differences in the AGDap measure ( P = 0.59)., Conclusion: Our study confirmed a significant relationship between reduced AGDas and late manifestations of TDS, providing further support to the association between prenatal androgen deficiency and late-onset reproductive disorders., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Human Reproductive Sciences.)

Adrenocortical carcinoma (ACC) is a rare disease among children. Our goal was to identify prognostic biomarkers in 48 primary ACCs from children (2.83 ± 2.3 y; mean age ± SD) by evaluating the tumor stage and outcome for an age of diagnosis before or after 3 years, and association with ACC cluster of differentiation 8 positive (CD8 + ) cytotoxic T lymphocytes (CD8 + -CTL) and Ki-67 immunohistochemical expression (IHC). Programmed death 1(PD-1)/Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) in ACC was analyzed in a second, partially overlapping cohort ( N = 19) with a similar mean age. All patients and control children were carriers of the germline TP53 R337H mutation. Survival without recurrence for less than 3 years and death unrelated to disease were excluded. Higher counts of CD8 + -CTL were associated with patients diagnosed with ACC at a younger age and stage I, whereas a higher percentage of the Ki-67 labeling index (LI) and Weiss scores did not differentiate disease free survival (DFS) in children younger than 3 years old. No PD-1 staining was observed, whereas weakly PD-L1-positive immune cells were found in 4/19 (21%) of the ACC samples studied. A high CD8 + -CTL count in ACC of surviving children is compelling evidence of an immune response against the disease. A better understanding of the options for enhancement of targets for CD8 + T cell recognition may provide insights for future pre-clinical studies.