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Anti-Müllerian hormone (AMH) has become a pivotal subject in the study of testicular descent, maturation, integrity, and male fertility. Recent studies explored its roles and implications across various domestic species. A prominent approach involved the understanding of the modulation of AMH in reproductive disorders, including cryptorchidism. While substantial findings have been reported in dogs, ruminants, swine, and horses, data on AMH in feline cryptorchidism remains limited. Here, we aimed to bridge this gap by comparing AMH serum levels among cryptorchid, healthy intact, and castrated tomcats, employing an enzyme-linked immunosorbent assay (ELISA) kit for quantification. In addition, AMH expression in retained and descended testes was evaluated through immunohistochemistry, with positive staining quantified via pixel analysis in two distinct regions of interest: the seminiferous tubule and the interstitial space. Furthermore, tissue samples were subjected to histological evaluation and morphometric analysis, which included the calculation of seminiferous tubule areas (STA) and assessment of Johnsen scores. Thus, the relationship between AMH expression, altered testicular histology, and impaired spermatogenesis could be examined. The expression of AMH in retained and descended testes, was investigated, and the relationship between AMH expression, altered testicular histology, and impaired spermatogenesis was examined. Mean serum AMH levels differed significantly (P < 0.001) across the different groups being 15.35 ± 4.66 ng/mL (mean ± SD) in healthy intact tomcats (n = 15), 25.55 ± 2.86 ng/mL (mean ± SD) in cryptorchids (n = 10) and below 0.015 ng/mL in castrated cats (n = 10). STAs and Johnsen scores were significantly reduced in retained testes when compared to descended gonads (P < 0.01). Furthermore, serum AMH was negatively correlated with both the STA (ρ = -0.725, P < 0.001) and the Johnsen scores (ρ = -0.699, P < 0.001), suggesting its potential value for tissue integrity and spermatogenesis evaluation. In addition, positive immunostaining was significantly higher in retained testes (P < 0.05), especially in the interstitial space (P < 0.01), suggesting an involvement of the Leydig cells. Additionally, the increased interstitial expression was linked to the degree of tissue degeneration and the impaired spermatogenesis being negatively corelated with both Johnsen scores (ρ = -0.309, P < 0.01) and STA (ρ = -0.208, P < 0.05). Our findings underscore the potential of AMH in assessing testicular health and reveal possible interspecific differences, stressing the need for further investigation in cats., Competing Interests: Declaration of interest The authors have no conflict of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Persistent stallion-like behavior is a common sign of cryptorchidism in supposed geldings. The presence of testicular tissue can be evaluated by analyzing hormones such as testosterone and anti-Müllerian hormone (AMH). Here, we used hormonal analysis to investigate relationships between the likely presence of testicular tissue and stallion-like behavior in samples submitted from presumptive geldings (n = 1,202), retrospectively. Most geldings with stallion-like behaviors had serum concentrations of testosterone (851/1,056; 80.6 %) and AMH (682/877; 77.8 %) below the laboratory reference range for cryptorchids (< 60 pg/mL and ≤ 0.15 ng/mL for testosterone and AMH, respectively). A total of 13 samples (13/716; 1.8 %) showed AMH concentrations typical for geldings but testosterone above the cryptorchid range. Conversely, 31 samples (31/716; 4.3 %) had high AMH, suggesting cryptorchidism, but testosterone concentrations implied no testicular tissue. Among the cryptorchid stallions, the AMH and testosterone concentrations did not vary based on the season. However, age categories affected the concentration of both hormones among the presumptive true cryptorchid stallions. The results of this study demonstrate that undesirable behavior in geldings is rarely associated with the presence of testicular tissue, as assessed by these two hormonal biomarkers. This information highlights the complexity of behavior and demonstrates that persistent stallion-like behavior in geldings could be related to factors other than the presence of testicular tissue., Competing Interests: Declaration of competing interest None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper., (Copyright © 2024. Published by Elsevier Inc.)

Context: Anti-Mullerian hormone (AMH) was originally described in the context of sexual differentiation in the male fetus but has gained prominence now as a marker of ovarian reserve and fertility in females. In this mini-review, we offer an updated synopsis on AMH and its clinical utility in pediatric patients., Design and Results: A systematic search was undertaken for studies related to the physiology of AMH, normative data, and clinical role in pediatrics. In males, AMH, secreted by Sertoli cells, is found at high levels prenatally and throughout childhood and declines with progression through puberty to overlap with levels in females. Thus, serum AMH has clinical utility as a marker of testicular tissue in males with differences in sexual development and cryptorchidism and in the evaluation of persistent Mullerian duct syndrome. In females, serum AMH has been used as a predictive marker of ovarian reserve and fertility, but prepubertal and adolescent AMH assessments need to be interpreted cautiously. AMH is also a marker of tumor burden, progression, and recurrence in germ cell tumors of the ovary., Conclusions: AMH has widespread clinical diagnostic utility in pediatrics but interpretation is often challenging and should be undertaken in the context of not only age and sex but also developmental and pubertal stage of the child. Nonstandardized assays necessitate the need for assay-specific normative data. The recognition of the role of AMH beyond gonadal development and maturation may usher in novel diagnostic and therapeutic applications that would further expand its utility in pediatric care., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Objectives: Antimullerian hormone (AMH) causes regression of the mullerian ducts in the male fetus. The appendix testis (AT) is a vestigial remnant of mullerian duct origin, containing both androgen (AR) and estrogen (ER) receptors. The role of both AMH and AT in testicular descent is yet to be studied. We investigated the possible association of AMH with AT size, the AR and ER, and their expression in the AT, in congenital cryptorchidism., Methods: A total of 26 patients with congenital unilateral cryptorchidism and 26 controls with orthotopic testes were investigated, and 21 ATs were identified in each group. AMH and insulin-like three hormone (INSL3) concentrations were measured with spectrophotometry. AR and ER receptor expression was assessed with immunohistochemistry using monoclonal antibodies R441 for AR and MAB463 for ER. For the estimation of receptor expression, the Allred Score method was used., Results: AMH concentrations did not present significant differences between patients with congenital cryptorchidism and the controls. Also, no correlation was found between AMH, INSL3, and AT length. Allred scores did not present significant differences. However, expression percentiles and intensity for both receptors presented significant differences. Three children with cryptorchidism and the highest AMH levels also had the highest estrogen receptor scores in the AT., Conclusions: No association was found between AMH and the studied major parameters. However, higher AMH concentrations, in combination with higher estrogen receptor scores in the AT, may play a role in cryptorchidism in some children. Larger population samples are needed to verify this observation., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: to explore the association of plasma concentrations of bisphenol A (BPA), bisphenol S (BPS), and bisphenol F (BPF) with unilateral cryptorchidism. In addition, to analyze selected demographic and intraoperative characteristics., Design: Retrospective analysis to determine plasma concentrations of total BPA, BPS and BPF using gas chromatography - mass spectrometry (GC-MS) among prepubertal boys with cryptorchidism and prebupertal male control subjects. During operation, the size, turgor and location of the cryptorchid testes were assessed., Main Outcome Measure: Plasma concentrations of total BPA, BPS and BPF., Results: In children with cryptorchidism, plasma levels of BPA, BPS and BPF were significantly higher compared to the control subjects. For BPA, it was: median value: 9.95 ng/mL vs . 5.54 ng/mL, p<0.05. For BPS, it was: median value: 3.93 ng/mL vs . 1.45 ng/mL, p<0.001. For BPF, it was: median value: 3.56 ng/mL vs . 1.83 ng/mL, p<0.05. In cryptorchid group, BPA was detected in 61.4% samples, BPS in 19.3% and BPF in 19.3%. All the three bisphenols were detected in plasma samples of both the healthy subjects and the study cohort. In the latter group, we found significant higher levels of BPA in boys from urban areas. We found a weak positive correlation between the levels of BPS and BPF and reduced turgor of the testes. Furthermore, results showed weak positive correlations between BPA and BPS levels and the age of the children as well as between BPS and BPF concentrations and the place of residence., Conclusions: Results provide a first characterization of prepubertal boys suffering from cryptorchidism and exposed to different kind of bisphenols. Our study suggests that cryptorchid boys are widely exposed to BPA and, to a lesser extent, also to its alternatives, such as BPS and BPF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Komarowska, Grubczak, Czerniecki, Hermanowicz, Hermanowicz, Debek and Matuszczak.)

Background: Maldescended testes or cryptorchidism is a genital birth defect that affects 2-9% of all male new-borns. Over the last 40 years there have been reports of increased prevalence in countries like the US, the UK and the Scandinavian countries. This possible increase has in some studies been linked to a foetal exposure to chemical pollutants. In this matched case-control study, we analysed maternal serum samples in early pregnancy for three different organochlorine compounds, to investigate whether the levels were associated with the risk of cryptorchidism., Method: Maternal serum samples taken during the first trimester of pregnancy from 165 cases (boys born with cryptorchidism) and 165 controls, matched for birth year and maternal age, parity and smoking habits during the pregnancy, were retrieved from the Southern Sweden Maternity Biobank. The samples were analysed for 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153), dichlorodiphenyltrichloroethane (p,p'-DDE) and hexachlorobenzene (HCB), using gas chromatography mass spectrometry. Associations between exposure and cryptorchidism were evaluated by conditional logistic regression., Results: We found no statistically significantly associations between exposure to these compounds and cryptorchidism, either when the exposure variables were used as a continuous variable, or when the exposure levels were divided in quartiles., Conclusion: We found no evidence of an association between maternal levels of PCB-153, p,p'-DDE or HCB during the pregnancy and the risk of having cryptorchidism in the sons., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Laminin 5 and collagen IV are the main compounds of the extracellular matrix of the germinal epithelium. The purpose of this study was to evaluate the concentration of these two markers of fibrosis in the plasma of boys with congenital unilateral cryptorchidism., Materials and Methods: The study group comprised 43 boys aged 1-3 years with congenital unilateral cryptorchidism. The control group included 54 healthy, age matched boys, admitted for planned hernioplasty. To assess laminin 5 and collagen IV in the plasma of boys with unilateral cryptorchidism, we used a new biosensor with Surface Plasmon Resonance Imaging technique detection., Results: The median concentration of laminin 5 and collagen IV in the serum of boys with congenital, unilateral cryptorchidism was higher than in boys with normal scrotal testis. The difference was statistically significant (p < 0.0001). We did not notice a correlation between a higher position of the testicles in the inguinal and/or their condition and levels of laminin 5 and collagen IV in the plasma., Conclusion: Laminin 5 and collagen IV concentrations in the plasma were higher in patients with congenital unilateral cryptorchidism. We believe that in the future, our results could be compared with fertility level in adulthood., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The purpose of this study was to evaluate the predictive value of haematologic parameters for testicular survival in torsion. Children with testicular torsion (TT) treated in Beijing Children's Hospital from January 2006 to December 2018 were enrolled in this study. Patient data collected in this study included age, symptom duration, preoperative preparation time, cryptorchidism testicular torsion or not, spermatic cord torsion degree, orchiectomy/orchiopexy, testicular volume 3 months after operation by ultrasound in orchiopexy patients and haematologic parameters. The orchiopexy group comprised of 54 patients with a mean age of 135.6 ± 43.73 months, and the orchiectomy group included 58 patients with a mean age of 119.36 ± 60.82 months. The multivariate analysis showed that symptom duration (Odds Ratio = 1.11, p < 0.001), spermatic cord torsion degree (Odds Ratio = 1.006, p = 0.002) and mean platelet volume (MPV; Odds Ratio = 3.697, p = 0.044) were significant predictors of orchiectomy. The cut-off value for MPV during window time for orchiectomy was 10.55 fl (10 -9  L) and provided a sensitivity of 47.8% and a specificity of 92.6%. This study found that symptom duration, spermatic cord torsion degree and MPV could be indicators of testicular viability in testicular torsion. MPV can provide valuable information before operation which can guide doctors and family members of the patients to select the appropriate treatment., (© 2019 Blackwell Verlag GmbH.)

The matrix metalloproteinases are enzymes capable of remodeling of extracellular matrix, and modulate the behavior of cells. Maturation of gubernaculum and spermatogenesis demand proper equilibrium of metalloproteinases and their inhibitors. The aim of this survey was to investigate the levels of matrix metalloproteinase type 1 (MMP-1) and matrix metalloproteinase type 2 (MMP-2) in the plasma of children with unilateral cryptorchidism along with levels of Insulin-like Peptide 3 (INSL3) and inhibin B. INSL3 have a role in gubernaculum development. Inhibin B is produced by Sertoli cells, and its levels reflect the status of the testis germinative epithelium. Fifty boys with an undescended testicle, aged 1-4 years (median = 2.4 years) were enrolled into the study. Fifty boys with inguinal hernia aged 1-4 years, served as controls (median age = 2.1 years). Investigators assessed the MMP-1 and MMP-2 concentrations using Surface Plasmon Resonance Imaging. The levels of INSL-3 and inhibin B were assessed using commercial enzyme-linked immunosorbent assay ELISA. The median concentration of MMP-1 and MMP-2 in the blood plasma of patients with unilateral cryptorchidism, was nearly 2-folds higher than in controls. The great area under the ROC curve with the cut off value of 0.865 for MMP-1, and 0.819 for MMP-2, indicates the high clinical sensitivity and specificity of the test of plasma levels of MMP-1 and MMP-2 for boys with cryptorchidism. The increased plasma levels of MMP-1 and MMP-2, probably reflect the level of apoptosis of the germ cells in undescended testicles, in response to the heat stress during the period of prepubertal testis development. In the group of cryptorchid boys, we found slightly lower concentrations of INSL3, without statistical significance and without correlation with MMP-1 and MMP-2 levels. There were no significant differences in the levels of inhibin B in the group of boys with cryptorchidism and boys with inguinal hernia and it also did not correlate with MMP-1 and MMP-2 concentrations.

Purpose: A meta-analysis including 11,900 cases showed that maternal gestational smoking was associated with increased risk of cryptorchidism. The aim of study was to investigate whether a hormone profile of cryptorchid boys and a supplementing histopathological evaluation of testicular biopsies could add detailed knowledge to the impact of maternal gestational smoking on pathogenesis of cryptorchidism., Methods: 601 cryptorchid boys aged 4 months to 14 years old were included. Because normal hormones have a pronounced age dependency, we compared results from boys whose mothers had smoked heavily (>10 cigarettes/day) during pregnancy with age matched cryptorchid controls of nonsmoking mothers (1:6). We studied: birthweight, germ-cell number/tubular cross section, frequency of germ cells positive for placental-like alkaline phosphatase (PLAP), gonadotropins and inhibin-B., Results: 501 boys were sons of nonsmokers, 72 boys of intermittent smokers and 28 boys of heavy smokers. 39%, 44% and 61% respectively had bilateral cryptorchidism. Compared to age-matched cryptorchid controls of nonsmoking mothers, sons of heavy smokers had lower birthweight (p = 0.006), germ-cell number/tubular cross section (p = 0.009), frequency of germ cells positive for PLAP (p = 0.037) and inhibin-B (p = 0.042)., Conclusions: All findings could be associated with placental dysfunction with altered human chorionic gonadotropin production well described in women smoking during pregnancy., Type of Study: Prognosis study (prospective cohort study with >80% follow-up)., Level of Evidence: Level 1., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Postnatal maturation of Sertoli cells is crucial for male fertility. The aim of this study was to assess the association between the Sertoli cell number per tubule cross-section (SC/T), the serum level of the Sertoli cell-produced inhibin B, and the A-dark spermatogonia number per tubule (Ad/T) in cryptorchid boys. Forty infant cryptorchid boys aged 4-35 months (median: 13 months) were included in the study. During orchiopexy, blood samples for serum inhibin B, luteinizing hormone (LH), and follicle stimulating hormone (FSH) and testicular biopsies were obtained. Histological sections were evaluated by quantitative immunohistochemical and immunofluorescence analysis including VASA and SOX9 (Sertoli cell marker) in order to measure the tubular germ cell number (G/T), Ad/T, and SC/T. The SC/T correlated negatively with age (p < 0.0002) and positively with G/T, Ad/T, inhibin B, FSH, and LH (all p < 0.01). Inhibin B correlated with LH (p < 0.0001), but not with FSH (p = 0.2077). The SC/T:G/T ratio positively correlated with age (p < 0.0001). Boys with Ad spermatogonia at surgery had a higher number of Sertoli cells compared to boys without Ad spermatogonia. In conclusion, a correlation between Sertoli cell number and inhibin B was proven, indicating that inhibin B possibly reflects the function of Sertoli cells in infant cryptorchid boys., (© 2019 S. Karger AG, Basel.)

Background: Studies examining the association of anogenital distance (AGD), a biomarker of prenatal androgen exposure, with sexual development in children are lacking., Objective: To assess the association between AGD measures and reproductive outcomes, including puberty onset, testicular volume, reproductive hormone levels, and urogenital malformations in boys aged 9-11 years., Materials and Methods: A cross-sectional study was conducted among children belonging to the Spanish Environment and Childhood (INMA) Project, a population-based birth cohort study. The present sample included 279 boys for whom data were available on AGD, pubertal stage, testicular volume, and relevant covariates. Out of the boys with AGD data, 187 provided a blood sample for hormone analysis. AGD was measured from the center of the anus to the base of the scrotum. Pubertal development was assessed according to Tanner stage of genital development (G1-G5), and testicular volume was measured with an orchidometer., Results: After adjusting for potential confounders, logistic regression analysis showed that AGD was positively associated with testicular volume but not with Tanner stage (>G1 vs. G1), serum hormone levels, or undescended testis. Regardless of their age, body mass index, and Tanner stage (G1 or >G1), boys with longer AGD showed increased odds of a testicular volume >3 mL (OR = 1.06, 95%CI = 1.00-1.19 per 10% increment in AGD; and OR = 3.14, 95%CI = 0.99-9.94 for AGD >42 mm vs. <33 mm)., Discussion: Longer AGD was associated with testicular growth, an indicator of gonadarche, but not with other reproductive outcomes., Conclusions: Although AGD was positively associated with testicular volume, it remains unclear whether AGD predicts testis size at puberty or is related to puberty onset., (© 2018 American Society of Andrology and European Academy of Andrology.)

Background: Cryptorchidism is a common condition of childhood, and it is known to impair fertility potential. However, the underlying mechanisms remain unclear., Methods: This study constructed two cryptorchid rat models to investigate the roles of apoptosis and autophagy in testicular impairment induced by cryptorchidism. Pregnant rats were randomly divided into three groups. Group I: non-treated rats were used as controls. Group II: injected with drug Flutamide (Flu) 25 mg/kg/bw/d from gestation day (GD) 11-19. Group III: daily intragastric administration of 750 mg/kg/bw/d di-2-ethylhexylphosphate (DEHP) from GD 7-19. The cubs were feed normally and the testes were excised on postnatal day (PND) 30., Results: Our results demonstrated cryptorchidism models induced noticeable decreased fertility, significantly reduced sperm count, increased sperm abnormality rate, decreased testosterone and severe testicular damage in histomorphology. Intriguingly, the level of apoptosis marker FAS, Cytochrome C and caspase-3 increased in Flu-induced and DEHP-induced groups. DEHP-induced treatment simultaneously increased the number of autophagosomes and the levels of autophagy marker LC3-II and p62. Significant decrease of autophagy gene (LC3-II and p62) expression is found in Flu-induced rats testes., Conclusion: Taken together, deficient autophagy is involved in testicular spermatogenesis damage of cryptorchidism rats. And this autophagy defect is caused by deficient degradation.

Purpose: To evaluate the concentration of 20S proteasome in the blood plasma of boys with cryptorchidism., Methods: Patients-50 boys aged 1-4 years (median = 2.4 years) with unilateral cryptorchidism. The control group-50 healthy, age-matched boys (aged 1-4 years, median = 2.1 years), admitted for planned herniotomy. In our study, we used a novel technique Surface PLASMON RESONANCE Imaging., Results: The median concentration of 20S proteasome in the blood plasma of boys with cryptorchidism was 2.5-fold higher than in boys with inguinal hernia. We noticed statistically significant difference between 20S proteasome levels in boys with cryptorchidism up to 2 years old and above 2 years old., Conclusions: We believe that the 20S proteasome concentrations in the blood plasma of boys with cryptorchidism reflect the heat-induced apoptosis of germ cells.

Background: Cryptorchidism, the most common male genital abnormality observed in paediatrics, might often be associated with long-term functional consequences and can even reoccur after a successful orchidopexy. Serum markers that identify cryptorchid boys with gonadal dysfunction early should be useful in a decision-making process. Inhibin B, produced during all of childhood but altered in cryptorchid subjects, appears strictly related to Sertoli cells, and its levels directly reflect the status of the testis germinative epithelium. Unfortunately, its precise roles in bilateral and unilateral cryptorchidism are still debated and being unravelled. Herein, we report the most current knowledge about inhibin B in both healthy boys and those with cryptorchidism to discuss and clarify its potential clinical applications., Discussion: Inhibin B represents a simple and repeatable serum marker and it seems to well asses the presence and function of the testicular tissue. Testicular tissue in prepubertal age is largely made up of Sertoli cells; inhibin B, coming from working Sertoli cells, allows to indirectly evaluate their function. Besides, inhibin B is produced throughout childhood, even before puberty, in contrast with central hormones, and it is not influenced by androgens during puberty, in contrast with other testicular hormones. Although further studies are needed, low levels of inhibin B have been related with low testicular score and/or with consistent alterations of testicular parameters at histological examination. This means that inhibin B could be an indirect marker of testicular functions that could even replace testicular biopsies, but current data are inconsistent to confirm this potential role of inhibin B in cryptorchidism., Conclusion: Inhibin B represents an effective candidate for early identification of testicular dysfunction after orchidopexy for cryptorchidism. Unfortunately, current data cannot exactly clarify the real role of inhibin B as a predictor of future testicular function in cryptorchidism and future long-term follow-up studies, with repeated inhibin B checks both in cryptorchid and in formerly cryptorchid children and adolescents, will permit to assess if previous normal levels of inhibin B would match with future normal pubertal development and fertility potential.

Context: Hypothalamic kisspeptin signaling plays a critical role in the initiation and maintenance of reproductive function. Biallelic mutations in the coding sequence of KISS1R (GPR54) have been identified in patients with idiopathic hypogonadotropic hypogonadism, but it is unknown whether biallelic variants can also be associated with related reproductive disorders., Case Description: A missense homozygous variant (c.890G>T p.R297L) in KISS1R was identified in a child who presented with microphallus and bilateral cryptorchidism. This variant has been reported to reduce, but not abolish, postreceptor signaling in vitro. Biochemical evaluation during the neonatal period revealed low testosterone levels. By 11 years and 8 months, the boy began demonstrating increases in testicular volume. By 17 years and 3 months, his testicular volume was 20 mL; his penile length was 7.3 cm; and he had adult levels of circulating gonadotropins and testosterone., Conclusion: This case report associates biallelic loss-of-function mutations in KISS1R with normal timing of adolescent puberty. Because these coding sequence variants occurred in a patient with microphallus and cryptorchidism, they demonstrate different levels of dependence of the hypothalamic-pituitary-gonadal cascade on kisspeptin signaling at distinct times in the reproductive life span. The suppression of the hypothalamic-pituitary-gonadal cascade during early life but not adolescence suggests that the mini puberty of infancy depends more on kisspeptin-induced, gonadotropin-releasing hormone-induced luteinizing hormone secretion than does adolescent puberty.

The synthesis of anti-Müllerian Hormone (AMH) by the Sertoli cells in males is crucial for sexual differentiation. There are no studies on AMH in Camelids. The objectives of this research were to 1) compare AMH serum concentrations in prepubertal and adult male alpacas and 2) determine the effect of castration on these concentrations in adult males to provide a validation of a commercial AMH test in alpacas. Serum samples were obtained from 15 prepubertal animals (5 for each age groups of 6, 7 and 8 months) and from 5 adult males (age 5-9 years), pre- and 24 h post-castration. AMH was determined with a quantitative ELISA according to the manufacture's instructions. There was not significant difference (P < 0.05) in AMH level (pg/ml) between pre-pubertal (549.9 ± 120.8, 789.4 ± 172.3, 597.5 ± 177.3 for ages 4, 7, and 8 months, respectively) and adult alpacas (938.7 ± 175.9). In adult males, AMH concentration decreased significantly following castration (P < 0.05) (938.7 ± 383.5 pg/ml) pre-castration, and 222.1 ± 116.5 pg/ml) after castration). There was a positive correlation between testosterone levels and AMH. In conclusion, the quantitative assay used is a reliable test to determine AMH in alpacas. The AMH level in prepubertal and adult alpacas appear to not differ, contrarily from other mammals, this requires further investigation. The decrease in serum AMH concentrations after castration suggests that measurement of this hormone can be used to diagnose bilateral cryptorchid or hemicastrated unilateral cryptorchid animals in this species., (Published by Elsevier Inc.)

Cryptorchidism and testicular tumours are very common disorders in dogs genitalia. The aim of the present study was o obtain an overview of serum 17β-oestradiol, anti-Muellerian hormone (AMH) and testosterone levels in intact dogs compared to dogs with different testicular tumours and dogs with cryptorchidism. Testosterone, AMH and 17β-oestradiol concentrations were measured in peripheral and local spermatic venous blood in dogs with unilateral cryptorchidism (n=8), dogs with neoplastic testicular diseases (n=8) and in a control group of mature intact dogs (n=8). Results confirmed significantly higher concentrations of testosterone in local venous blood (control group: right testicle (RT) 46.23 ± 40.88 ng/ml and left testicle (LT) 50.76 ± 43.76 ng/ml; cryptorchid group: RT 23.91 ± 22.79 ng/ml and LT 10.52 ± 7.37 ng/ml; tumour group: RT 37.26 ± 25.26 ng/ml and LT 44.86 ± 19.03 ng/ml) (p<0.05) compared to their concentrations in peripheral blood (PB) in a control (4.92 ± 3.3 ng/ml) and in a cryptorchid group (0.89 ± 0.78 ng/ml), but not in the tumour group (11.37 ± 10.86 ng/ml). However, we have found increased level of testosterone in PB in the tumour group compared to its PB concentrations in the control or the cryptorchid group. Concentrations of AMH in PB observed in the cryptorchid group was 54.98 ± 30.07 μg/ml and in the control group was 6.49 ± 3.24 μg/ml (p<0.05). The same was observed in the case of local blood concentrations, which were significantly higher in the cryptorchid group (RT 51.92 ± 30.59 μg/ml; LT 46.33 ± 34.86 μg/ml) (p<0.05). We also observed high oestradiol concentrations in the cryptorchid group in both peripheral and local blood (PB: 30.86 ± 20.28 pg/ml; RT: 55.71 ± 34.7 pg/ml; LT: 78.99 ± 47.72 pg/ml), and even higher in the tumour group (PB: 52.46 ± 34.02 pg/ml; RT: 188.16 ± 132.67 pg/ml; LT: 297.14 ± 245.56 pg/ml). AMH has been shown to be a specific biomarker of gonadal tumours originated in Sertoli cells. It is also useful marker for confirmation of the existence of a functional cryptorchid testis. According to us, the scientific work dealing with a disorder of testicular descent in dogs, regarding the evaluation of sex hormones levels and the formation of the testes using modern diagnostic methods, significantly contribute to the clarification of some processes, leading to pathophysiological disturbances during this process., (Copyright© by the Polish Academy of Sciences.)

Background/objective: To compare the curative effect of single-stage and two-stage Fowler-Stephens (F-S) laparoscopic orchidopexy for intraabdominal high testis and explore the appropriate surgical approach., Methods: We performed a prospective analysis of the clinical data of 28 patients who underwent F-S laparoscopic orchidopexy for intraabdominal high testis in our department from May 2012 to April 2015, including 15 cases of the single-stage F-S operation and 13 cases of the two-stage F-S operation. By comparing the two groups preoperative and postoperative (6 months) clinical data of testicular position, testicular volume, and sex hormone levels [testosterone (T), follicle stimulating hormone (FSH), and estradiol (E 2 )], we analyzed the difference in efficacy between the two procedures., Results: Twenty-eight patients completed laparoscopic surgery, no case was converted, and no testis was excised. All patients were followed up for 9-25 months after the operation, with an average follow-up of 16.2 months. The postoperative testicular volume of the single-stage and two-stage F-S groups was not significantly reduced (p>0.05). In both groups, the postoperative T levels were significantly increased compared to the preoperative levels (p<0.05), while the FSH and E 2 levels were significantly decreased (p<0.05). The differences in testicular volume and T, FSH, and E 2 levels between the two surgical procedures were not significant (p>0.05). In the single-stage F-S group, the testes were located in the scrotum in 13 cases and retracted to the lower groin in two cases. In the two-stage F-S group, the testes were located in the scrotum in 12 cases and retracted to the lower groin in one case. The difference in postoperative testicular position between the two groups was not significant (p>0.05)., Conclusion: In the case of testis with good collateral circulation, single-stage F-S laparoscopic orchidopexy had the same safety and efficacy as the two-stage F-S procedure. Surgical options should be based on comprehensive consideration of intraoperative testicular location, testicular ischemia test, and collateral circumstances surrounding the testes. Under the appropriate conditions, we propose single-stage F-S laparoscopic orchidopexy be preferred. It may be appropriate to avoid unnecessary application of the two-stage procedure that has a higher cost and causes more pain for patients., (Copyright © 2017. Published by Elsevier Taiwan.)

Objective: To investigate the effect of micro-dissection testicular sperm extraction (microTESE) for patients with non-obstructive azoospermia (NOA) and the indications of the strategy., Methods: This retrospective study included 196 cases of NOA undergoing microTESE in our center from September 2014 to March 2017. We recorded the sperm retrieval rate (SRR) and analyzed its correlation with the patients' age, testis volume, level of blood follicle-stimulating hormone (FSH), and etiological factors., Results: Testicular sperm were successfully retrieved from 87 (44.4%) of the patients. No significant correlation was found between the SRR and the patients' age, testis volume, or blood FSH level (P >0.05). As regards etiological factors, the SRR was 100% (29/29) in the patients with orchitis, 66.7% (16/24) in those surgically treated for cryptorchidism, 55.6% (10/18) in those with other secondary testis lesions, 60.0% (3/5) in those with AZFc deletion, 40.9% (9/22) in those with severe idiopathic testicular atrophy, 21.4% (12/56) in those with idiopathic NOA, 20.5% (8/39) in those with Klinefelter's syndrome, and 0% (0/3) in those with other abnormal karyotypes., Conclusions: MicroTESE is an effective strategy for sperm retrieval in NOA patients, and the SRR is correlated with etiological factors but not with the FSH level or testis volume of the patients.

Background: In previous reports no differences in Leydig and Sertoli cell function were found between congenital undescended testis (CUDT) and acquired UDT (AUDT) on the basis of serum levels of LH, testosterone, FSH or inhibin B. This study tried to detect differences in Leydig and Sertoli cell function between CUDT and AUDT using insulin-like peptide 3 (INSL3) and anti-Müllerian hormone (AMH)., Method: 118 men with a history of UDT (CUDT N=55 (6/55 bilateral), AUDT N=63 (15/63 bilateral)) were investigated. Differences between CUDT and AUDT, influence of age at surgery in CUDT, and effect of spontaneous descent or orchiopexy in AUDT were evaluated., Results: For INSL3, no significant differences were found. AMH levels in bilateral CUDT were significantly lower compared with bilateral AUDT (6.4 (1.7-11.4) vs 13.2 (6.1-30.1) μg/l, p=0.02). AMH levels in unilateral CUDT were significantly higher than in bilateral CUDT (12.1 (2.4-43.7) vs. 6.4 (1.7-11.4) μg/l, p=0.02)., Conclusion: No differences in Leydig cell function on the basis of INSL3 levels between the different UDT groups were found. Sertoli cell function evaluated by AMH, was more negatively affected in bilateral CUDT in comparison with bilateral AUDT and unilateral CUDT., Level of Evidence Rating: Level III Treatment Study., (Copyright © 2017. Published by Elsevier Inc.)

Objective: To investigate the levels of serum anti-Müllerian hormone (AMH) and inhibin B (INHB) in patients with unilateral cryptorchidism before and after orchidopexy., Methods: This study included 58 cases of unilateral cryptorchidism treated by orchidopexy and 32 healthy controls. Before and at 6 months after surgery, we measured the length and circumference of the penis, the volume of the undescended testis, and levels of serum AMH and INHB., Results: There were statistically significant differences between the unilateral cryptorchidism and healthy control groups in the levels of serum AMH (［102.80 ± 17.35 vs 108.76 ± 13.64］ ng/ml, P<0.05) and INHB (［70.24 ± 5.73］ vs ［ 77.72 ± 5.94］ pg/ml, P<0.05) at the baseline, but not at 6 months after orchidopexy (AMH: ［109.76 ± 17.25］ vs ［108.03 ± 14.13］ ng/ml, P>0.05; INHB: ［75.76 ± 5.94］ vs ［77.63 ± 5.99］ pg/ml, P>0.05). No remarkable differences were observed between the unilateral cryptorchidism and healthy control groups in the preoperative penile length (［2.05 ± 0.23］ vs ［2.11 ± 0.22］ cm, P>0.05), penile circumference (［3.91 ± 0.23］ vs ［3.99 ± 0.20］ cm, P>0.05) and volume of the undescended testis (［0.45 ± 0.02］ vs ［0.46 ± 0.02］ ml, P>0.05), or in the postoperative penile length (［2.09 ± 0.23］ vs ［2.16 ± 0.22］ cm, P>0.05), penile circumference (［4.00 ± 0.25］ vs ［3.98 ± 0.19］ cm, P>0.05) and volume of the undescended testis (［0.45 ± 0.02］ vs ［0.45 ± 0.02］ ml, P>0.05). Compared with the baseline, the cryptorchidism patients showed markedly increased levels of serum AMH (［102.80 ± 17.35］ vs ［109.76 ± 17.25］ ng/ml, P<0.05) and INHB (［70.24 ± 5.73］ vs ［75.76 ± 5.94］ pg/ml, P<0.05) after orchidopexy., Conclusions: Orchidopexy can elevate the levels of serum AMH and INHB and protect the testicular function of cryptorchidism patients.

In cryptorchid boys, failures in germ cell development have been clearly established. Some studies reported some abnormalities in Sertoli cells morphology but the results regarding their endocrine secretion remain controversial. To compare testicular hormone levels in young boys with and without cryptorchidism, we performed a cross-sectional hospital-based study. From surgery appointment records, we identified a case group of boys with unilateral or bilateral cryptorchidism and a control group undergoing dental care, minor osteoarticular or dermal surgery. Blood samples were withdrawn during the surgical procedure to perform testosterone, inhibin B and anti-müllerian hormone (AMH) immunoassays. We included 27 cryptorchid boys and 27 controls aged of 26.6 vs. 24.2 months, respectively (p = 0.172) far from the post-natal mini-puberty and the corresponding hormonal surges. Age-adjusted AMH and inhibin B levels were significantly lower in cryptorchid than in control boys (AMH: 87 ng/mL vs. 135 ng/mL; p = 0.009, inhibin B: 97 pg/mL vs. 133 pg/mL; p = 0.019, respectively). Moreover, AMH and inhibin B levels were significantly lower in the bilateral cryptorchid subgroup, being 50% lower than in the controls (p = 0.011 and 0.019, respectively) and while both hormones levels were independent in controls, they became strongly correlated in bilateral cryptorchid boys (R² = 0.75, p = 0.001). In addition, testosterone levels were still detectable in some boys, with significantly lower levels in cryptorchid group than in controls. Overall, 2-year-old cryptorchid patients presented a simultaneous and significant drop in AMH and inhibin B levels, suggesting a functional defect of Sertoli cells. This deficiency appeared more pronounced in bilateral cryptorchidism and thus, regarding the pivotal role of Sertoli cells in germ cell development, it may explain the compromised fertility found later in men born with such a malformation., (© 2017 American Society of Andrology and European Academy of Andrology.)

Context: Undescended testes at birth may be caused by testosterone deficiency during fetal development. It is unclear whether the process of failed descent contributes to permanent endocrine impairment., Objectives: To evaluate the impact of age at treatment of undescended testes on endocrine and spermatogenic testicular function in middle-aged men., Patients and Methods: Reproductive hormone and semen data of 357 men with previously undescended testes were evaluated with respect to age at correction of testicular position and compared to those of 709 controls with eutopic testes at birth and normozoospermia., Results: Men with undescended testes had higher mean Luteinizing Hormone levels (p < 0.0001) and lower mean testosterone levels (p = 0.003) compared to controls. They also had lower bi-testicular volumes, higher Follicle Stimulating Hormone levels, and lower sperm concentrations (all p < 0.0001). Lowest mean sperm concentrations were found in subjects with bilateral undescended testes. Normal sperm concentrations were found in 21 % of cases (in 27 % of men with unilateral and in 12 % with bilateral undescended testes), while oligozoospermia was diagnosed in 44 %, and azoospermia in 35 % (in 28 % with unilateral, 46 % with bilateral undescended testes). Subjects with reduced semen quality had higher gonadotropin levels than those with normozoospermia. Age at correction (median: 6 years (1-39)) was inversely correlated with bi-testicular volumes and sperm concentrations, and positively correlated with FSH and LH, but not with serum testosterone., Conclusion: Latent, rarely decompensated hypogonadism is a potential long-term consequence of undescended testes, besides infertility and testicular cancer, preferentially affecting subjects with delayed or unsuccessful correction of testicular position. Impaired Leydig cell function is likely to contribute to compromised fertility. These observations support correction of cryptorchidism during early infancy.

Patients with very low sperm count through direct sperm examination can exhibit extreme oligozoospermia or cryptozoospermia (after centrifugation). The management of these patients is a real challenge for both clinicians and biologists. In this retrospective and comparative cohort study, we compared the andrological phenotype of patients with extreme alterations of spermatogenesis and assessed whether the origin of spermatozoa (testicular or ejaculate) had any influence on intracytoplasmic sperm injection (ICSI) outcomes. A total of 161 ICSI cycles were performed using ejaculated spermatozoa from 75 patients with extreme oligozoospermia (EOS) or cryptozoospermia (CS) and 150 ICSI cycles using extracted testicular spermatozoa from 74 patients with non-obstructive azoospermia (NOA). Physical, hormonal, ultrasound assessments, and ICSI outcomes were performed in each group. Cryptorchidism was significantly more frequent in the NOA group (60.8% vs. 22.6%, p = 0.001). FSH levels were significantly higher [18.9 IU/L (5.9-27.0) vs. 15.3 IU/L (9.0-46.5), p = 0.001] and the majority of inhibin B levels measured were found mostly undetectable in the NOA group as compared to EOS/CS group (31.1% vs. 10.7%, p = 0.0004). Moreover, we found no significant differences in the respect to the fertilization rates (48.9% and 43.3%, p = 0.43), implantation rates (17.4% and 15.9%, p = 0.77), and percentage of top quality embryo (22.4% and 20.4%, p = 0.73) between the two groups. The clinical pregnancy rates per embryo transferred were comparable in both groups (28.3% and 27.4%, p = 0.89). In this study, we showed for the first time a different andrological phenotype between EOS/CS and NOA groups. Indeed, cryptorchidism was significantly more frequent with more severe endocrine parameters found in the NOA group. These results reflect a more profound alteration in spermatogenesis in NOA patients. However, there was no difference in ICSI outcomes between NOA and EOS/CS groups., (© 2017 American Society of Andrology and European Academy of Andrology.)

Objective: Testicular dysgenesis syndrome (TDS) comprises testicular germ cell cancer, cryptorchidism and some cases of male infertility and hypospadias, which can be linked to impairment of intrauterine gonadal development. Among histological signs of TDS, large Leydig cell (LC) clusters (micronodules) are frequently present. This study aimed to investigate possible associations of LC micronodules with the presence of Reinke crystals and hormonal function of LCs, the latter primarily reflected by serum concentrations of luteinising hormone (LH) and testosterone, in patients with TDS., Design: A retrospective study of 101 andrological patients with TDS (infertility with and without a history of cryptorchidism or presence of germ cell neoplasia in situ) and 20 controls with normal testis histology and LC-function. Archived testicular biopsies were re-evaluated for the presence of LC micronodules and Reinke crystals and the findings were correlated with testis size and serum concentrations of LH, follicle-stimulating hormone (FSH), testosterone, inhibin B, estradiol and sex hormone binding globulin (SHBG)., Results: TDS patients with bilateral LC micronodules had significantly lower concentrations of LH, FSH and inhibin B, a lower testosterone/LH-ratio and smaller testis sizes compared to TDS-patients lacking this feature. Presence of LC micronodules was correlated with a lower number of Reinke crystals, while cryptorchid testes had a significantly higher number of crystals than normally descended TDS testes., Conclusion: LC micronodules appear to be a compensatory mechanism caused by androgenic failure and are presumably driven by high concentrations of LH. A relative paucity of Reinke crystals in LCs within micronodules in normally descended TDS testes may be a feature of recently renewed immature Leydig cells. The increased number of Reinke crystals in LCs in testes that were either undescended at birth or are persistently undescended could indicate an impairment of LC renewal in cryptorchidism.

Objective: To investigate the influence of unilateral cryptorchidism on the levels of serum anti-müllerian hormone (AMH) and inhibin B in children., Methods: We enrolled 65 patients with unilateral cryptorchidism and 45 healthy children in this study. We measured the length and circumference of the penis, the testis volume in the cryptorchidism side, and the levels of serum AMH and inhibin B at the age of 6 and 12 months, respectively., Results: Compared with the healthy controls, the patients with unilateral cryptorchidism showed significant decreases at 12 months in serum AMH (［108.06±12.40］ vs ［103.26±17.57］ ng/ml, P<0.05) and inhibin B (［77.43±5.66］ vs ［70.21±5.69］ pg/ml, P<0.05). No statistically significant differences were found in the length and circumference of the penis and the testis volume in the cryptorchidism side at 6 and 12 months (P>0.05), or in the levels of serum AMH and inhibin B at 6 months (P>0.05)., Conclusions: Unilateral cryptorchidism affects the gonadal function of the patient, and orchiopexy should be timely performed in order to reduce its impact.

Introduction: A transient increase in gonadotropins and testosterone during mini-puberty causes gonocytes to differentiate into Ad spermatogonia, which establish male germ cell memory and male-specific DNA methylation pathways. Over half of patients with unilateral cryptorchidism and the majority of patients with bilateral cryptorchidism display an abnormal spermiogram, which indicates that unilateral cryptorchidism is a bilateral disease; therefore, it represents a serious andrological problem. The aim of this study was to evaluate relationships between hormonal parameters and testicular biopsy findings in boys with cryptorchidism., Method: Seventy-one boys (median age 15 months; range 7-65 months) who underwent orchidopexy (24% had bilateral cryptorchidism) were tested for serum LH, FSH, and inhibin B. With ipsilateral testis biopsy histology, we determined the tubular fertility index (TFI), Ad spermatogonia counts, and Ad/tubular index (Ad/T). We compared age groups (<18 vs. >18 months old); groups with and without Ad spermatogonia; groups with unilateral and bilateral cryptorchidism; and extreme groups with high infertility risk (HIR; n = 12; TFI <0.2; Ad/T = 0) and low infertility risk (LIR; n = 9; TFI >0.9; Ad/T>0.02)., Results: Of the specimens, 38% had no Ad spermatogonia. Age was significantly negatively correlated with TFI and Ad/T, but positively correlated with FSH. Median LH values were significantly higher in LIR than in HIR groups. Unilateral and bilateral cryptorchidism showed similar TFI, Ad/T, and hormone concentrations. The areas under ROC curves for FSH, LH, and inhibin B (0.66, 0.601, and 0.599, respectively) showed low diagnostic value for predicting HIR (no Ad spermatogonia)., Conclusion: Our observation of lower plasma LH levels in the group with the most pronounced testicular pathology was the opposite of what we would have expected if testicular pathological changes were caused by a primary gonadal defect. Therefore, low plasma LH levels in the HIR group confirmed the notion that this group of patients with cryptorchidism had hypogonadotropic hypogonadism. The estimated incidence of defective mini-puberty in boys with cryptorchidism could be as high as 50%. Testicular biopsies from boys with cryptorchidism lacked Ad spermatogonia. Fertility parameters worsened with age. Significantly lower basal LH in the HIR group indicated hypogonadotropic hypogonadism. Serum hormone levels could not predict histological biopsy findings., (Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Context: The G protein-coupled receptor GPRC6A is an emerging effector with multiple endocrine roles, including stimulation of T production from the testis. Recently, two men with an inactivating mutation (F464Y) of GPRC6A have been identified, and they showed primary testicular failure and deranged spermatogenesis. Furthermore, one of them also reported cryptorchidism at birth. In addition, a polymorphism (rs2274911, Pro91Ser) in GPRC6A is associated with prostate cancer, a typical androgen-sensitive cancer., Objective: To study the possible association between rs2274911 polymorphism and male fertility and/or cryptorchidism. Design, Patients, Settings: A total of 611 subjects, including 343 infertile patients, 197 normozoospermic controls, and 71 cryptorchid newborns, were retrospectively selected., Methods: Sequencing analysis for rs2274911 polymorphism and F464Y mutation, and serum levels of FSH, LH, and T were assessed. In vitro functional studies for rs2274911 and F464Y were also performed., Results: Homozygous subjects for the risk allele A of rs2274911 had a 4.60-fold increased risk of oligozoospermia and 3.52-fold increased risk of cryptorchidism. A significant trend for increased levels of LH in the GA and AA genotypes, compared with GG homozygotes, was detected in men with azoospermia/cryptozoospermia (P for trend = .027), further supporting an association with primary testicular failure. The mutation F464Y was found in one cryptorchid child (one in 71; 1.41%). Functional studies showed that the A allele of rs2274911 and the F464Y substitution were associated with lower exposition of the receptor on the cell membrane and a reduced downstream phosphorylation of ERK1/2 with respect to wild type., Conclusion: Our results suggest that GPRC6A inactivation or sub-function contributes to reduced exposure to androgens, leading to cryptorchidism during fetal life and/or low sperm production in adulthood.

The present study aimed to evaluate the effect of trans-Resveratrol on spermatogenesis. Male Kunming suckling mice (10 days old) were surgically rendered cryptorchid and subcutaneously injected with trans-Resveratrol at doses of 5, 10, 20, and 40 µg/g/day as groups I, II, III, and IV, respectively, for 35 days. Animals in the control group received 10 µL/mouse/day of olive oil. Serum estradiol, testosterone, FSH, and LH levels were measured on day 45. Tissue analysis and sperm morphological abnormalities analysis were done. Results showed that in the control group and group I only spermatogonia and primary spermatocytes were present, whereas spermatogenesis was totally restored in groups II, III, and IV. Sperm counts in groups III and IV were remarkably higher than the control group (P<0.05). The morphological abnormalities in resveratrol-treated groups were higher than the mature mice. Serum estradiol levels in the resveratrol-treated groups were not significantly different from the control group, but were lower than the mature mice (P<0.05). There was no significant difference in serum testosterone levels between the resveratrol-treated groups and mature mice, but the levels in the resveratrol-treated groups was significantly lower than the control group (P<0.05). No significant influence of trans-Resveratrol was observed on serum FSH levels in all cryptorchid mice. Serum LH levels in groups I, II, and III were higher than the control group. These results indicate that trans-Resveratrol restores spermatogenesis in cryptorchid mice. In addition, proteomic analysis between the 20 μg/g/day resveratrol-treated group and the control group was carried out, and five kinds of proteins (BAF250, ZFP261, CHD1L, RBBP9, and SOHLH2) were identified. The expression of SOHLH2 increased, while that of BAF250, ZFP261, CHD1L, and RBBP9 decreased in the 20 µg/g/day resveratrol-treated group, indicating that SOHLH2 may contribute to testicular germ cell differentiation., (© 2015 International Federation for Cell Biology.)

Purpose: Boys with cryptorchidism have overall increased gonadotropin and decreased serum inhibin B levels compared to normal. Serum inhibin B levels, produced by Sertoli cells, may reflect the state of germinative epithelium in cryptorchid testes. We evaluated whether serum inhibin B levels differed between boys with unilateral vanished testis and those with unilateral cryptorchidism., Materials and Methods: Blood samples from 297 boys 1.5 to 5 years old were included, of whom 222 had unilateral cryptorchidism, 29 had unilateral vanished testis and 46 had undergone unilateral orchiopexy 1 year previously. Serum inhibin B levels were measured using a commercially available ELISA kit and were compared to normal range., Results: Serum inhibin B levels in boys with unilateral vanished testis were not different from those with unilateral cryptorchidism. Serum inhibin B values were above the normal median in 43% of boys previously operated on for unilateral cryptorchidism, compared to 17% at surgery (p = 0.0003). The percentage of patients with inhibin B levels below normal range was 14% in those with unilateral vanished testis, 23% in those with unilateral cryptorchidism and 11% in those who had undergone orchiopexy 1 year previously for unilateral cryptorchidism. The percentage of boys with inhibin B levels above normal median was 24% in those with unilateral vanished testis, 17% in those with unilateral cryptorchidism and 43% in those who had undergone orchiopexy. However, in boys with a vanished testis the frequency of serum inhibin B above normal median was only 5% before age 1.5 years, after which the rate was 67% (p = 0.0022)., Conclusions: Our findings may reflect the development of contralateral testicular hypertrophy in boys with unilateral vanished testis. The initial low inhibin B values may be explained by impaired total number of Sertoli cells. Serum inhibin B values also indicated that in 6-month to 5-year-old boys with cryptorchidism orchiopexy was beneficial for the germinative epithelium., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: In recent publications of boys with cryptorchidism, gonadotropins are higher and serum inhibin-B lower than normal. To some extent, serum values of inhibin-B reflect the state of germinative epithelium in cryptorchid testes. The aim of the present study was to evaluate the impact of unilateral orchiopexy on levels of gonadotropins and inhibin-B and correlate the hormone findings to the histopathology of the unilateral undescended testis., Methods: 50 boys (mean age: 1 year and 2 months) operated for unilateral cryptorchidism had blood samples for serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and inhibin-B taken preoperatively and 3 months to 2 years postoperatively. Testicular biopsies were performed at orchiopexy. The total germ cell number per transverse tubule and presence of adult dark spermatogonia were estimated., Results: Preoperatively, 8 patients had impaired inhibin-B levels. In contrast with the expected normal physiological decline, 16 patients had an absolute rise in serum inhibin-B level postoperatively. The 4 patients who normalized the preoperative impaired serum level of inhibin-B all had low germ cell number in the testis at time of operation. Nine patients had preoperatively elevated serum levels of both LH 0.5-2.3 IU/l (mean: 1.0 IU/l) and FSH 1.3-2.2 IU/l (mean: 1.6 IU/l). Eight of these patients normalized both LH and FSH serum values postoperatively. None of the 4 boys with impaired inhibin-B level that did not normalize after surgery had elevated gonadotropins., Conclusion: Orchiopexy in unilateral cryptorchidism had a clear impact on the serum level of inhibin-B and gonadotropins of 32% and 16%, respectively., (Copyright © 2014 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: Cryptorchidism, the most frequent congenital malformation in full-term male newborns, increases the risk of hypofertility and testicular cancer. Most cases remain idiopathic but epidemiological and experimental studies have suggested a role of both genetic and environmental factors. Physiological testicular descent is regulated by two major Leydig hormones: insulin-like peptide 3 (INSL3) and testosterone., Objectives: To study the endocrine context at birth as a reflection of late pregnancy in isolated idiopathic cryptorchidism and to analyse the possible disruptions of INSL3 and/or testosterone., Methods: From a prospective case-control study at Nice University Hospital, we assessed 180 boys born after 34 weeks gestation: 52 cryptorchid (48 unilateral, 4 bilateral; 26 transient, 26 persistent), and 128 controls matched for term, weight and time of birth. INSL3 and testosterone were measured in cord blood and compared in both groups as were other components of the pituitary-gonadic axis: LH, HCG, FSH, AMH and SHBG., Results: INSL3 was decreased in cryptorchid boys (P = 0·031), especially transient cryptorchid (P = 0·029), while testosterone was unchanged as were the other hormones measured. INSL3 was significantly decreased (P = 0·018) in the group of 20 with nonpalpable testes compared with the group of 21 with palpable testes (15 suprascrotal, five inguinal, one high scrotal) according to Scorer classification. In the whole population, INSL3 correlated positively with LH and negatively with AMH, but with no other measured hormones., Conclusions: INSL3 but not testosterone is decreased at birth in idiopathic cryptorchidism, especially in transient forms. This hormonal decrease may contribute to the impaired testicular descent along with genetic and anatomical factors. Whether foetal environment (nutritional and/or toxicological) interferes with INSL3 secretion in humans remains to be confirmed., (© 2014 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Study Question: Does a relationship exist between insulin-like peptide 3 (INSL3) and selected environmental endocrine disruptors (EEDs) in human cord blood (cb)?, Summary Answer: In the whole population (cryptorchid and control boys) cbINSL3 correlated negatively with cb free bisphenol A (BPA) providing indirect evidence for an impact of EEDs on fetal Leydig cell INSL3 production., What Is Known Already: INSL3 is a major regulator of testicular descent. This hormone has been shown to be decreased in cord blood from boys with idiopathic cryptorchidism, the most frequent male malformation. Fetal exposure to several EEDs has been suspected to be involved in the occurrence of idiopathic cryptorchidism., Study Design, Size, Duration: Correlations between cb INSL3 or testosterone and cb free bioactive BPA and maternal milk polychlorinated biphenyls (PCB153), dichlorodiphenyldichloroethylene (DDE), and monobutyl phthalate (mBP) were assessed in newborn boys in a prospective case-control study. All boys (n = 6246) born after 34 weeks of gestation were systematically screened at birth for cryptorchidism over a 3-year period (2002-2005), and a diagnosis of cryptorchidism confirmed by a senior paediatrician., Participants/materials, Setting, Methods: We studied 52 cryptorchid (26 transient, 26 persistent) and 128 control boys born at two hospitals in southern France. INSL3 was assayed in CB by a modified validated enzyme-linked immunosorbent assay. Testosterone was measured in CB after diethyl-ether extraction by means of ultra-pressure liquid chromatography-tandem mass spectrometry. Free cbBPA was measured after an extraction step with a radioimmunoassay validated after comparison of values obtained by high-pressure liquid chromatography-mass spectrometry. The xenobiotic analysis in mothers' milk was performed after fat extraction by gas chromatography-mass spectrometry., Main Results and the Role of Chance: EED concentrations were not increased in the cryptorchid versus control group although a trend for increased mBP (P = 0.09) was observed. In the whole study population, cb levels of BPA correlated negatively with INSL3 (P = 0.01; R² = 0.05) but not with testosterone. No other EED correlated with INSL3 or with testosterone., Limitations, Reasons for Caution: The levels of BPA and INSL3 in cb may not reflect chronic fetal exposure to EEDs. The deleterious impact of EEDs on fetal testicular descent during specific windows of development has yet to be demonstrated., Wider Implications of the Findings: The negative correlation between cb free BPA and INSL3 provides indirect evidence for an impact of EEDs on human fetal Leydig cell INSL3 production and points to cbINSL3 as a possible target of EED action during fetal testis development., (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: To evaluate the relationship between unilateral or bilateral criptorchidism, patient age, primary location of the gonad and modality of treatment with testicular volume and hormonal status at 18 years in patients diagnosed and treated for cryptorchidism during childhood., Materials and Methods: Testicular volume, LH, FSH, and testosterone were evaluated in 143 young men at 18 years treated in childhood for unilateral (n=103) or bilateral (n=40) cryptorchidism., Results: Unilateral cryptorchidism: Location of testis was prescrotal in 36 patients, inguinal in 52 and non-palpable in 15. The mean volume was 9.7 mL compared to 16.2 L. for the spontaneously descended testicle in unilateral cryptorchidism. However, 22 patients who received HCG had a significantly bigger testis (11.8 mL.) than those treated with primary surgery (9.2 mL). The results showed a significant positive correlation between testicular volume and patient age at treatment. Bilateral cryptorchidism: Location of testis was prescrotal in 34 cases, inguinal in 40 and 6 patients with non-palpable testicles. Mean volume at 18 years was 12.9 mL, greater than unilateral cryptorchid testis (9.7 mL) but smaller than healthy contralateral in unilateral cases (16.2 mL). There were significant differences in the testicular growth for bilateral patients with testicular descent after being treated with HCG (14.4 mL) in respect with those untreated (11.1 mL) or those who underwent primary surgery (11.4 mL). There was a significant positive correlation between the testicular volume and palpable (12.4 mL) or non-palpable testis (10.4 mL). There was a correlation between unilateral or bilateral cryptorchidism and levels of FSH., Conclusions: Testicular volume and hormonal function at 18 years for patients diagnosed and treated for cryptorchidism during childhood are strongly influenced by whether the undescended testis was unilateral or bilateral. Location of the testes at diagnosis or age of initial treatment exerts no definite effect on testicular volume improvement r hormonal levels at 18 years of age.

Objective: Open testicular biopsy (OTB) is one of the options to accurately assess fertility potential of the undescended testis. The aim of the study was to investigate consequences of OTB in prepubertal rats on their adulthood fertility., Methods: Thirty-eight prepubertal male rats were divided into three groups depending on day 20 procedure. The first group was the control group, the second sham operated and the third has left OTB. Bilateral orchiectomy was performed on day 70 to all groups, with determination of serum inhibin B and follicle stimulating hormone (FSH). Removed testes were compared according to the weight, volume, spermatogenesis, histological and apoptotic changes in both testes with differences in serum levels of inhibin B and FSH., Results: Ipsilateral testicular weight, volume, and spermatogenesis reduction with a reduction of tubular number, diameter and germinative epithelium was found in OTB group. Significant increase in apoptotic index was found in biopsied testis without compensatory hypertrophy of contralateral testis. Differences of inhibin B and FSH were not statistically significant among three groups., Conclusion: OTB in prepubertal rats has detrimental effects on fertility in adulthood. It does not cause compensatory hypertrophy of the contralateral testis nor does it disturb serum levels of inhibin B and FSH., (Copyright © 2014 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Geographical differences in the occurrence of diseases in male reproductive organs, including malformation in reproductive tract, between Denmark and Finland have been reported. The reason for these differences is unknown, but differences in exposure to chemicals with endocrine-disrupting abilities have been suggested. Among these chemicals are perfluoro-alkylated substances (PFASs), a group of water- and grease-repellent chemicals used in outdoor clothes, cookware, food packaging, and textiles. In this study, we, therefore, investigated differences in PFAS exposure levels between Denmark and Finland and the association between cord blood PFAS levels and congenital cryptorchidism. Boys from a joint ongoing prospective birth cohort study were included. We analyzed PFAS levels in cord blood serum samples collected from 29 Danish boys with congenital cryptorchidism, 30 healthy Danish matched controls recruited from 1997 to 2001, 30 Finnish cases, and 78 Finnish healthy matched controls recruited from 1997 to 1999. Additionally, 48 Finnish cases recruited from 2000 to 2002 were included. Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) were detected in all the 215 Danish and Finnish cord blood samples with significantly higher levels being observed in the Danish samples (medians: PFOA, 2.6 ng/ml and PFOS, 9.1 ng/ml) than in the Finnish samples (medians: PFOA, 2.1 ng/ml and PFOS, 5.2 ng/ml). We found no associations between cord blood PFOA and PFOS levels and congenital cryptorchidism after adjustment for confounders. Our data indicate that women in Denmark and Finland are generally exposed to PFOA and PFOS but there are differences in exposure levels between countries. We found no statistically significant association between cord blood PFOA and PFOS levels and congenital cryptorchidism; however, our study was small and larger studies are warranted.

Purpose: In the pathogenesis of sub-fertility/infertility and testicular cancer related to undescended testes, oxidative stress, inflammation and autoimmunity are important factors. Therefore, the present study was designed to determine serum oxidative stress markers and carbonic anhydrase (CA) II autoantibodies in boys with undescended testes (UDT), and to investigate the relationship between these parameters., Methods: Serum CA II autoantibody titers, malondialdehyde (MDA), ischemia modified albumin (IMA), protein carbonyl content and soluble CD40 ligand (sCD40L) levels were measured in 59 boys with UDT and 30 healthy subjects., Results: MDA levels were significantly higher in the UDT group compared with the control group (p = 0.003). There was no significant difference between serum IMA, sCD40L or protein carbonyl levels. CA II autoantibody titers in the UDT group were significantly higher compared with those of the control group (p = 0.048). A weak positive correlation was determined between anti-CA II antibody titers and MDA and IMA levels (p = 0.041, p = 0.005, respectively)., Conclusions: MDA is the most reliable and decisive biochemical marker displaying oxidative damage in undescended testes, and an autoimmune response may be triggered by oxidative stress against CA II during the UDT process.

Reasons for Performing Study: Cryptorchidism affects 2-8% of male horses and the affected testis undergoes a disruption of normal spermatogenesis. The underlying molecular changes are poorly understood in the cryptorchid equine testis., Objectives: Compare the expression of anti-Müllerian hormone (AMH), anti-Müllerian hormone receptor (AMHR2), androgen receptor (AR), cyclin kinase inhibitor (CDKN1B), connexin 43 (Cx43), 3β hydroxysteroid dehydrogenase/Δ(5) -Δ(4) - isomerase (3βHSD), P450c17 hydroxylase/lyase (P450c17) and cytochrome P450 aromatase (P450arom) in the undescended testis of cryptorchid stallions with that of normal stallions., Methods: Undescended, abdominal testes from four cryptorchid stallions between 2 and 3 years of age were collected during routine castrations along with normally descended testes from normal stallions between 2 and 3 years of age (n = 7). Samples were analysed by immunohistochemistry and quantitative real-time PCR., Results: Cryptorchid testes had increased AMH and AMHR2 immunolabelling when compared with normal testes, which indicates failure of maturation of Sertoli cells and/or lack of testosterone suppression. Failure of Sertoli cell maturation in the cryptorchid testis may also be attributed to AR abnormalities and/or a consequence of lack of testosterone suppression due to decreased 3βHSD. Cyclin-dependent kinase (CDKN1B) was not expressed in Sertoli cells of cryptorchid testes suggesting that Sertoli cells are still proliferating, which is also a characteristic of the immature testis. In addition, Cx43 expression is decreased in the cryptorchid testis, indicating a disruption in intercellular communication., Conclusions: Undescended testes of cryptorchid horses present characteristics of immaturity suggesting that the failure of Sertoli cell maturation may be a consequence of cryptorchidism., Potential Relevance: This study provides a better understanding of the effect of cryptorchidism on testicular function in stallions., (© 2012 EVJ Ltd.)

Hypospadias is a frequent congenital malformation, which severity is connected to the spongiosum divergence. Biological and anatomical explorations are necessary, before the recourse to the surgeon, in posterior hypospadias, familial hypospadias, but also in any type of hypospadias associated with cryptorchidism, bifid scrotum, micropenis less than 20mm (full-term newborn), or any other anomaly (skeletal, renal, cardiac…). The "mini-puberty", occurring in the first 4-6 months of life, is a period of intense gonadotropic activity in male newborns. It allows an easy investigation of the testicular function in boys with hypospadias. Hormonal evaluation (testosterone, AMH) should be done the first day of life. Let us remind that a newborn with "hypospadias" and bilateral cryptorchidism must be considered, until proved otherwise, as a girl with congenital adrenal hyperplasia., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Anti-Müllerian hormone (AMH), a homodimeric glycoprotein, is secreted early in fetal life when it exerts a crucial function in sexual differentiation. The secretion of AMH in male humans persists after birth and is characterized by high prepubertal concentrations followed by a significant decrease at the onset of puberty. The expression of AMH in the normal and cryptorchid equine testis is well characterized but data regarding circulating AMH concentrations are lacking. The objectives of this study were to determine serum AMH concentrations in neonatal colts and fillies, prepubertal colts, and postpubertal stallions, and to evaluate variations in serum AMH related to season and gonadal status of stallions. In addition, we examined the presence and determined concentrations of AMH in seminal plasma of mature stallions. Serum AMH concentrations were significantly higher in neonatal colts than in neonatal fillies. Moreover, concentrations of AMH are high in prepubertal colts whereas significantly lower concentrations were detected after puberty. In intact mature stallions, season influenced AMH concentrations with significantly higher concentrations during spring and summer. Serum AMH concentrations were significantly higher in cryptorchid stallions compared with intact stallions or geldings. Finally, AMH was identified in seminal plasma of intact mature stallions, but there was no significant correlation between serum and seminal plasma AMH concentrations. In conclusion, serum AMH concentration varies with sex in the neonatal period, postnatal sexual development and season, and serum AMH concentration can be used as a biomarker for the presence of testicular tissue., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Men with Down's syndrome (DS) have an increased risk of cryptorchidism, but the mechanisms causing its onset are not clear. Cryptorchidism causes a primary testiculopathy responsible for infertility. SPAG5 mRNA is predominantly expressed in testis in pachytene spermatocytes. This observation prompted us to evaluate the expression of SPAG5 gene in five DS men with cryptorchidism and five normal healthy men (controls) by quantitative real-time PCR in peripheral blood leukocytes. We found that SPAG5 is over expressed in the five men with DS and cryptorchidism compared with five age- and sex-matched normal controls. This finding suggests that the increased expression of this gene may play a pathogenic role durin testicular development in subjects with DS and cryptorchidism.

Purpose: The main objectives of this retrospective cohort study were to evaluate reproductive endocrine and semen profiles before and after simple orchiectomy in patients with unilateral postpubertal cryptorchidism and to investigate the relationship between hormone levels and histopathology of the removed testis., Methods: We evaluated 40 adult males who were admitted to our clinic, between 2001 and 2007, with unilateral undescended testis. Right orchiectomy was performed in 27 patients and left orchiectomy in 13. Semen analysis, serum inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were examined in before and 3 months after orchiectomy. Orchiectomy materials were evaluated histopathologically., Results: Semen parameters, as well as testosterone and LH levels, did not change in any histopathological subgroups in the postoperative follow-up. In patients with maturation arrest, mean serum inhibin B level statistically significantly decreased from 160.9 to 83.5 pg/ml, and mean FSH level significantly increased from 4.8 to 7.6 mIU/ml after orchiectomy (p value, 0.008 and 0.008, respectively). Though, the levels were still within the normal range of the two hormones., Conclusions: Simple orchiectomy does not have any effect on semen parameters and testosterone level in patients with postpubertal cryptorchidism. The change in inhibin B and FSH levels after orchiectomy in patients with maturation arrest is not clinically significant.

Purpose: In recent series of boys with cryptorchidism gonadotropin levels have been higher and serum inhibin B levels have been lower than normal. To some extent the serum values of inhibin B reflect the state of germinative epithelium in cryptorchid testes. We evaluated whether blood samples of gonadotropins and inhibin B as well as histopathology could be used to classify undescended testes., Materials and Methods: A total of 69 boys (median age 2 years) who underwent surgery for bilateral cryptorchidism had blood samples taken preoperatively and 3 months to 2.1 years postoperatively. Testicular biopsies were performed bilaterally at orchiopexy. The average germ cell number per tubular transverse tubule was measured., Results: Group 1 included 17 patients with increased follicle-stimulating hormone levels. Serum follicle-stimulating hormone and luteinizing hormone decreased significantly after surgery. In 77% of patients (13 of 17) follicle-stimulating hormone levels were normalized. Of these boys 35% (6 of 17) had a low postoperative serum inhibin B. Group 2 consisted of 27 patients with a decreased germ cell number and/or low preoperative inhibin B, but not increased serum follicle-stimulating hormone or luteinizing hormone. There were no significant postoperative changes in follicle-stimulating hormone and luteinizing hormone. Of these boys 22% (6 of 27) had a low serum inhibin B postoperatively. In group 3 there were 25 patients with a normal germ cell number, normal preoperative serum inhibin B and normal gonadotropins. There were no significant changes in luteinizing hormone and follicle-stimulating hormone postoperatively. Only 1 boy in this group had a low postoperative serum inhibin B., Conclusions: Patients with increased gonadotropin levels may have testicular dysgenesis and some may benefit from early surgery. Patients with normal gonadotropin levels and a decreased germ cell number have transient hypothalamus-pituitary-gonadal hypofunction and a poor fertility prognosis. These patients may benefit from gonadotropin treatment after orchiopexy. Patients with normal gonadotropins, inhibin B and germ cell number have a good fertility prognosis after surgery., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to compare anti-Mullerian hormone (AMH) plasma levels in patients with azoospermia according to the physiopathology. In a prospective clinical study from April 2008 to March 2009 in University Hospital, we measured AMH levels in 49 consecutive patients with azoospermia. AMH plasma levels were correlated with FSH, inhibin B, bioavailable testosterone plasma levels and testicular volume and compared between nonobstructive azoospermia (NOA) and obstructive azoospermia (OA) and within four physiopathological subgroups of NOA: genetic, cryptorchidism, cytotoxic and unexplained. AMH, FSH, inhibin B, bioavailable testosterone plasma levels and testicular volumes were all related to each other. AMH plasma levels were lower in NOA relatively to OA. Lowest values were observed in cases of genetic NOA and on the other hand, the values observed in case of cytotoxic NOA were as high as the values observed in OA. FSH, inhibin B, bioavailable testosterone and testicular volume were not different between genetic and cytotoxic NOA. These results suggest that the decrease in AMH plasma levels is related to the origin of NOA, with low values in genetic NOA and values similar to OA in cytotoxic NOA. Further studies will be useful to understand the fine regulation of AMH production., (© 2011 Blackwell Verlag GmbH.)