Perspectives in Pediatric Pathology, Chapter 3. Testicular Development from Birth to Puberty: Systematic Evaluation of the Prepubertal Testis

Nistal, Manuel; Paniagua, Ricardo; González‐Peramato, Pilar; Reyes‐Múgica, Miguel

doi:10.2350/12-09-1255-pb.1

Cited by 14 publications

(7 citation statements)

References 95 publications

(142 reference statements)

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“…Histological analysis of the xenografts showed preservation of the testis tissue architecture and morphology, with well-defined seminiferous cords and interstitial compartments across all the experimental groups ( Figure 2 a–c). Spermatogonia are the most advanced germ cell type in prepubertal human testis [ 22 , 23 , 24 ]. At puberty, spermatogonia differentiate into spermatocytes, the latter give rise to spermatids; and subsequently, spermatids develop into spermatozoa [ 25 ].…”

Section: Resultsmentioning

confidence: 99%

Fertility Preservation in Childhood Cancer: Endocrine Activity in Prepubertal Human Testis Xenografts Exposed to a Pubertal Hormone Environment

Hutka

Kadam

Saen

et al. 2020

Cancers

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Survivors of childhood cancer are at risk for long-term treatment-induced health sequelae, including gonadotoxicity and iatrogenic infertility. At present, for prepubertal boys there are no viable clinical options to preserve future reproductive potential. We investigated the effect of a pubertal induction regimen with gonadotrophins on prepubertal human testis xenograft development. Human testis tissue was obtained from patients with cancer and non-malignant haematological disorders (n = 6; aged 1–14 years) who underwent testis tissue cryopreservation for fertility preservation. Fresh and frozen-thawed testis fragments were transplanted subcutaneously or intratesticularly into immunocompromised mice. Graft-bearing mice received injections of vehicle or exogenous gonadotrophins, human chorionic gonadotrophin (hCG, 20 IU), and follicle-stimulating hormone (FSH, 12.5 IU) three times a week for 12 weeks. The gross morphology of vehicle and gonadotrophin-exposed grafts was similar for both transplantation sites. Exposure of prepubertal human testis tissue xenografts to exogenous gonadotrophins resulted in limited endocrine function of grafts, as demonstrated by the occasional expression of the steroidogenic cholesterol side-chain cleavage enzyme (CYP11A1). Plasma testosterone concentrations (0.13 vs. 0.25 ng/mL; p = 0.594) and seminal vesicle weights (10.02 vs. 13.93 mg; p = 0.431) in gonadotrophin-exposed recipient mice were comparable to vehicle-exposed controls. Regardless of the transplantation site and treatment, initiation and maintenance of androgen receptor (AR) expression were observed in Sertoli cells, indicating commitment towards a more differentiated status. However, neither exogenous gonadotrophins (in castrated host mice) nor endogenous testosterone (in intact host mice) were sufficient to repress the expression of markers associated with immature Sertoli cells, such as anti-Müllerian hormone (AMH) and Ki67, or to induce the redistribution of junctional proteins (connexin 43, CX43; claudin 11, CLDN11) to areas adjacent to the basement membrane. Spermatogonia did not progress developmentally but remained the most advanced germ cell type in testis xenografts. Overall, these findings demonstrate that exogenous gonadotrophins promote partial activation and maturation of the somatic environment in prepubertal testis xenografts. However, alternative hormone regimens or additional factors for pubertal induction are required to complete the functional maturation of the spermatogonial stem cell (SSC) niche.

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Section: Resultsmentioning

confidence: 99%

Fertility Preservation in Childhood Cancer: Endocrine Activity in Prepubertal Human Testis Xenografts Exposed to a Pubertal Hormone Environment

Hutka

Kadam

Saen

et al. 2020

Cancers

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“…It is not until the third cycle of proliferation of the seminiferous epithelium (which takes place at puberty) that spermatozoa are formed and the testis develops its adult histologic appearance. 12 Premature maturation of the testicular parenchyma in young patients is a well-known phenomenon in the setting of precocious puberty, whether central (caused by premature activation of the hypothalamic gonadotropinreleasing hormone pulse generator, so-called "true" or gonadotropin-dependent precocious puberty), from hCGsecreting neoplasms, or due to the peripheral production of androgens by testicular, adrenal, or other neoplasms (so-called "precocious pseudopuberty" or gonadotropinindependent precocious puberty). 4,5,13 While testicular maturation typically occurs in a diffuse fashion throughout the testis in this setting, the maturation can be focal, as has been described in the seminiferous tubules immediately surrounding a Leydig cell tumor or Leydig cell hyperplasia 9,10 or in occasional reports of non-neoplastic cases of gonadotropin-independent precocious puberty; however, those cases do not have a clinically detectable mass.…”

Section: Discussionmentioning

confidence: 99%

“…While there are 2 successive waves of germ cell maturation that occur early in development, resulting in the sporadic appearance of more mature germ cells (eg, spermatocytes and occasionally early spermatids) in some of the seminiferous cords before puberty, these waves are temporary and incomplete. It is not until the third cycle of proliferation of the seminiferous epithelium (which takes place at puberty) that spermatozoa are formed and the testis develops its adult histologic appearance 12…”

Section: Discussionmentioning

confidence: 99%

Nodular Maturation of the Testis

Przybycin

Williamson

Kao

et al. 2021

American Journal of Surgical Pathology

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We have encountered a lesion of the pediatric testis, termed “nodular maturation,” that clinically mimics a testicular neoplasm causing ultrasound abnormalities that may lead to surgical excision. To our knowledge, it has only been described anecdotally in textbooks without a series or description in the literature. We, therefore, report 8 cases in pediatric patients emphasizing the clinical presentation, ultrasound findings, histologic features, and clinical follow-up information. Patients ranged in age from 5 to 11 years (mean: 7.9 y). Precocious puberty was identified in 1 patient as isolated penile enlargement without other signs; another had a history of McCune-Albright syndrome, but did not have signs of precocious puberty; others had no clinical manifestations. All patients had testicular abnormalities on ultrasound; 6 had a discrete lesion and 2 showed diffuse testicular enlargement. In the 6 cases with available data, mean size of the lesion on ultrasound was 0.9 cm (range: 0.4 to 1.7 cm). In the 3 cases for which macroscopic descriptions were available, no gross abnormalities were noted in the testicular parenchyma, despite the ultrasound findings. Histologically, nodular maturation occurred as a zone of more mature testicular parenchyma having larger, lumen-bearing seminiferous tubules that contrasted with the smaller, immature cords of the remaining parenchyma. The mature tubules showed germ cell maturation (to the level of late spermatids/spermatozoa in 6 cases), mature Sertoli cells, and, in 4 cases, admixed nodules of mature Leydig cells. Of the 6 patients with available follow-up information, none developed a testicular neoplasm. Given its ability to cause a lesion on ultrasound leading to surgical intervention, pathologists, radiologists, and urologists should be aware of nodular maturation.

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“…Histological study is necessary to evaluate damage of the testicular parenchyma in cryptorchidism. We must keep in mind that the testis is a dynamic structure with waves of proliferation and differentiation from birth to puberty (see Nistal and colleagues [45]). Testicular volume becomes 40-fold increased by the end of puberty.…”

Section: Lesions Of Undescended Testes In Childhoodmentioning

confidence: 99%

Perspectives in Pediatric Pathology, Chapter 14. Natural History of Undescended Testes

et al. 2016

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Perspectives in Pediatric Pathology, Chapter 3. Testicular Development from Birth to Puberty: Systematic Evaluation of the Prepubertal Testis

Cited by 14 publications

References 95 publications

Fertility Preservation in Childhood Cancer: Endocrine Activity in Prepubertal Human Testis Xenografts Exposed to a Pubertal Hormone Environment

Fertility Preservation in Childhood Cancer: Endocrine Activity in Prepubertal Human Testis Xenografts Exposed to a Pubertal Hormone Environment

Nodular Maturation of the Testis

Perspectives in Pediatric Pathology, Chapter 14. Natural History of Undescended Testes

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