Clinical aspects of histological and hormonal parameters in boys with cryptorchidism

Hildorf, Simone

doi:10.1111/apm.13247

Cited by 5 publications

(27 citation statements)

References 264 publications

(538 reference statements)

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“…Other classifications of gonocytes and primordial fetal germ cells, for example, pro-or prespermatogonia have been proposed (3,26,27), but no ubiquitous consensus regarding terminology has been reached. During the first trimester, gonocytes are mitotically active forming a quite homogenous cell population expressing markers typical of pluripotent cells including primordial germ cells such as KIT proto-oncogene (c-KIT), octamer-binding transcription factor 3/4 (Oct3/4), lin-28 homolog A (LIN28), homeobox protein Nanog (NANOG), antipodoplanin M2A antigen (D2-40), and placental alkaline phosphatase (PLAP) (3,25,(28)(29)(30)(31)(32)(33). This suggests that gonocytes are quite equivalent to primordial germ cells, both presenting the distinctive morphology of being large spherical cells with a prominent nucleus containing one or two nucleoli surrounded by a spherical shape cytosol (3,26,34).…”

Section: Normal Germ Cell Developmentmentioning

confidence: 99%

“…Cryptorchidism is the most prevalent congenital anomaly in boys and represents a well-characterized risk factor for infertility and testis cancer. Men with a history of cryptorchidism constitute a substantial proportion of 20%-27% of azoospermic men (1)(2)(3). Furthermore, men with a prior history of bilateral cryptorchidism exhibit considerably lower paternity rates, at 65% compared to men who experienced unilateral cryptorchidism (90%) and unaffected control men (93%) (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

“…Men with a history of cryptorchidism constitute a substantial proportion of 20%-27% of azoospermic men (1)(2)(3). Furthermore, men with a prior history of bilateral cryptorchidism exhibit considerably lower paternity rates, at 65% compared to men who experienced unilateral cryptorchidism (90%) and unaffected control men (93%) (3)(4)(5). The evidence is compelling that infertility in adulthood has a clear relation to the germ cell status in childhood (3,(6)(7)(8)(9)(10)(11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, men with a prior history of bilateral cryptorchidism exhibit considerably lower paternity rates, at 65% compared to men who experienced unilateral cryptorchidism (90%) and unaffected control men (93%) (3)(4)(5). The evidence is compelling that infertility in adulthood has a clear relation to the germ cell status in childhood (3,(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). In addition, boys with cryptorchidism face an elevated risk of testicular neoplasia later in life surpassing the risk observed in the general population (3,(16)(17)(18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

“…The evidence is compelling that infertility in adulthood has a clear relation to the germ cell status in childhood (3,(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). In addition, boys with cryptorchidism face an elevated risk of testicular neoplasia later in life surpassing the risk observed in the general population (3,(16)(17)(18)(19)(20)(21). Notably, the status of the germ cells is important, given that germ cell tumors constitute more than 95% of all reported testicular malignancies (22,23).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

The fate of germ cells in cryptorchid testis

Thorup,

Hildorf,

Hildorf

et al. 2024

Front. Endocrinol.

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Cryptorchidism in males constitutes a notable risk factor for both infertility and testicular cancer. Infertility in adulthood is closely linked to the germ cell status in childhood. Furthermore, the significance of germ cell status is important as more than 95% of all reported testicular malignancies are germ cell tumors. The review aims to elucidate the pathogenesis of germ cells in cryptorchid testes concerning their association with infertility and testicular malignancies. Impaired germ cell numbers are evident in cryptorchid testes even during antenatal and neonatal stages. In cryptorchidism there is a rapid decline in germ cell number within the first year of life, partially attributed to physiologic gonocyte apoptosis. Additionally, germ cells fail to differentiate normally during mini-puberty leading to reduced germ cell proliferation and delayed clearance of gonocytes from the seminiferous epithelium. Absence of germ cells in testicular biopsies occurs already 10 months of age and germ cell deterioration progressively worsens with approximately 50% of persisting cryptorchid testes lacking germ cells during puberty. The deficient germ cell maturation and proliferation leads to later infertility. Elevated temperature in the cryptorchid testes and also hormonal deficiency contribute to this phenomenon. Germ cell neoplasia in situ (GCNIS) originating during fetal development may manifest in rare cases associated with disorders of sexual development, chromosomal abnormalities in boys, specific syndromes, and teratomas that include cryptorchidism. In adults, the presence of GCNIS predominantly represents a new histology pattern before invasive germ cell cancer is demonstrated and is neither congenital nor related to abnormal gonocyte transformation.

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Section: Normal Germ Cell Developmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The fate of germ cells in cryptorchid testis

Thorup,

Hildorf,

Hildorf

et al. 2024

Front. Endocrinol.

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Anogenital distance in a cohort of 169 infant boys with uni- or bilateral cryptorchidism including 18 boys with vanishing testes

Cortes,

Fischer,

Hildorf

et al. 2024

Human Reproduction

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STUDY QUESTION Do different boys with different types of cryptorchidism exhibit different anogenital distances (AGDs)? SUMMARY ANSWER Length of AGD seemed to differ in different groups of patients with cryptorchidism. WHAT IS KNOWN ALREADY AGD, which is used as an indicator of prenatal androgen action, tends to be shorter in boys with cryptorchidism compared to unaffected boys. Shorter AGDs have also been reported in boys with hypospadias, in men with poor semen quality, and in men with testicular cancer. STUDY DESIGN, SIZE, DURATION A prospective descriptive cohort study was performed using data from consecutively selected boys with cryptorchidism (n = 169) operated in a single center over a period of 3 years (September 2019 to October 2022). PARTICIPANTS/MATERIALS, SETTING, METHODS AGD was measured in 169 infant boys, at 3 to 26 months of age, during anesthesia with a vernier caliper measuring the distance from the anus to the base of the scrotum (AGDAS) and from the anus to the anterior base of the penis (AGDAP) in two body positions according to the methods by ‘The Infant Development and the Environment Study’ (TIDES) and ‘Cambridge Baby Growth Study’, resulting in four mean values per patient (TIDES AGDAS/AP and Cambridge AGDAS/AP). Normal values for AGD by age were set by our hospital Department of Growth and Reproduction based on a large cohort of healthy infant boys (n = 1940). Testicular biopsies were performed at orchidopexy as a clinical routine. The germ cell number (G/T) and type Ad spermatogonia number (AdS/T) per cross-sectional tubule of at least 100 and 250 tubules, respectively were measured and related to normal samples. Blood samples were obtained by venipuncture for measuring serum LH, FSH, and inhibin B. They were analyzed in our hospital Department of Growth and Reproduction where the normal reference was also established. Correlations between the four mean AGD measurements for each boy were evaluated by Spearman rank correlation analyses. The AGD measurement of every boy was transferred to the multiple of the median (MoM) of the normal AGD for age and named MoM AGD. MAIN RESULTS AND THE ROLE OF CHANCE There were 104 boysoperated for unilateral, and 47 boys operated for bilateral, undescended testes, whereas 18 boys had vanished testis including one boy with bilateral vanished testes. Only 6% of cases with vanished testes had a MoM AGD higher than the normal median compared to 32% with undescended testes (P < 0.05). MoM AGD increased with the age at surgery for boys with vanished testis (Spearman r = 0.44), but not for boys with undescended testes (Spearman r = 0.14). Boys with bilateral cryptorchidism had longer AGDs and more often had hypogonadotropic hypogonadism than boys with unilateral cryptorchidism (P < 0.005) and (P < 0.000001). LIMITATIONS, REASONS FOR CAUTION Although being the largest published material of AGD measurements of infant boys with cryptorchidism, one limitation of this study covers the quite small number of patients in the different groups, which may decrease the statistical power. Another limitation involves the sparse normal reference material on G/T and AdS/T. Finally, there are currently no longitudinal studies evaluating AGD from birth to adulthood and evaluating childhood AGD in relation to fertility outcome. Our study is hypothesis generating and therefore the interpretation of the results should be regarded as exploratory rather than reaching definite conclusions. WIDER IMPLICATIONS OF THE FINDINGS The study findings are in agreement with literature as the total included group of boys with cryptorchidism exhibited shorter than normal AGDs. However, new insights were demonstrated. Boys with vanished testis had shorter AGDs compared to unaffected boys and to boys with undescended testes. This finding challenges the current concept of AGD being determined in ‘the masculinization programming window’ in Week 8 to 14 of gestation. Furthermore, boys with bilateral cryptorchidism had longer AGDs and more often had hypogonadotropic hypogonadism than boys with unilateral cryptorchidism, suggesting that the lack of fetal androgen in hypogonadotropic hypogonadism is not that significant. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used and no competing interests are declared. TRIAL REGISTRATION NUMBER The trial was not registered in an ICMJE-recognized trial registry.

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Downregulation of Serotonergic System Components in an Experimentally Induced Cryptorchidism in Rabbits

Jiménez-Trejo,

Arriaga-Canon,

Herrera

et al. 2024

IJMS

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Cryptorchidism (CO) or undescended testes is defined as the failure of one or both testes to be positioned inside the scrotum. Typically, cryptorchidism is detected at birth or shortly thereafter, and in humans, it is considered to be part of the testicular dysgenesis syndrome (TDS), a complex pathology regarding the male reproductive system that apparently involves the interaction of both genetic and environmental harmful factors, mainly during embryonic development. Serotonin (5-HT) is an ancient molecule that participates in a broad range of body functions, and in recent years, its importance in reproduction has started to be elucidated. In male pathologies such as infertility, varicocele, erectile dysfunction, and primary carcinoid tumors, an increase in 5-HT concentration or its metabolites in the blood, semen, and urine has been directly related; nevertheless, the role of 5-HT in CO remains unknown. In the present work, our goal was to answer two important questions: (1) whether some serotonergic system components are present in adult male Oryctolagus cuniculus (chinchilla rabbit) and (2) if there are changes in their expression in an experimental model of CO. Using histological, molecular, and biochemical approaches, we found the presence of some serotonergic system components in the adult chinchilla rabbit, and we demonstrated that its expression is downregulated after CO was pharmacologically induced. Although we did not test the role of 5-HT in the etiology of CO, our results suggest that this indoleamine could be important for the regulation of steroidogenesis and spermatogenesis processes in the chinchilla rabbit during adulthood. Finally, in parallel experimental series, we found downregulation of kynurenine concentration in COI rabbits when compared to control ones, suggesting that CO could be affecting the kynurenine pathway and probably testicular immune privilege which in turn could lead to infertility/sterility conditions in this disorder.

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Clinical aspects of histological and hormonal parameters in boys with cryptorchidism

Cited by 5 publications

References 264 publications

The fate of germ cells in cryptorchid testis

The fate of germ cells in cryptorchid testis

Anogenital distance in a cohort of 169 infant boys with uni- or bilateral cryptorchidism including 18 boys with vanishing testes

Downregulation of Serotonergic System Components in an Experimentally Induced Cryptorchidism in Rabbits

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