Precocious initiation of spermatogenesis in a 19-month-old boy with Hurler syndrome

Abstract

Mucopolysaccharidosis type IH (MPS IH) is a rare autosomal recessive lysosomal storage disorder. Haematopoietic stem cell transplantation (HSCT) has been proposed for the treatment of MPS IH patients and offers the possibility to grow into their adulthood. Precocious puberty has been described in few MPS patients. We report, to the best of our knowledge and for the first time, the initiation of the first waves of spermatogenesis fortuitously observed in seminiferous tubules of a pre-pubertal 19-month-old boy, affected by MPS IH and who did not present any clinical signs of precocious puberty. This patient benefited from testicular tissue cryopreservation before HSCT. Seminiferous tubule size, germ cell differentiation and Sertoli cell expression of androgen receptor and anti-müllerian hormone corresponded to the pattern observed in a pubertal boy. The Hurler syndrome may be responsible for the precocious initiation of spermatogenesis. A specific follow-up during childhood may be useful to confirm if such abnormal testis development is common in young boys with MPS IH and if it may lead to precocious onset of puberty in survivors despite HSCT. Furthermore, we have observed that Sertoli cell maturation (up-regulation of AR expression, down-regulation of AMH expression) occurred before the clinical signs of puberty and before the increase of testosterone plasmatic level.

Assessment of the architecture and integrity of frozen‐thawed testicular tissue from (pre)pubertal boys with cancer

“…Vimentin and Anti-Müllerian hormone for Sertoli cells; Androgen Receptor for Sertoli and Leydig cells; 3β-Hydroxysteroid dehydrogenase for Leydig cells) were maintained in human (pre)pubertal testicular tissue after thawing according to expected expression related to patient age, confirming the ability of our CSF to also preserve somatic cells after thawing. 42 However, it should be noted that PCNA expression was not detected in spermatogonia of several (pre)pubertal patients, both in fresh and frozen-thawed tissue, thus causing potential bias in interpretation of our data. Several hypotheses can be put forward to explain the absence of PCNA expression in spermatogonia and Sertoli cells: (i) loss of cellular proliferative capacity, (ii) lack of DNA repair expression induced by cryodamage, (iii) loss by necrosis of cells theoretically able of expressing PCNA.…”

Importance of the Androgen Receptor Signaling in Gene Transactivation and Transrepression for Pubertal Maturation of the Testis

“…The increase in AR expression happens in a testosterone-free environment, thus not inducing Sertoli cell maturation. If due to abnormal conditions, testosterone production is maintained during the expectedly “quiescent” period, AMH expression is inhibited, reflecting precocious Sertoli cell maturation [48,49].…”

“…As previously mentioned, the decrease in AMH expression at pubertal onset is indicative of Sertoli cell maturation. Despite the fact that AMH downregulation by androgens has been established a long time ago in all animals studied, including human [55,58,96,142], mouse [8,48,49,143], ram [144,145], pig [146,147], stallion [148], bovine [149,150], and tammar wallaby [151], it has not been until recently that the underlying mechanism of androgen action was described [30].…”

Reproduction in Animal Models of Lysosomal Storage Diseases: A Scoping Review

“…Another case report with MPS I revealed that ERT was safe for the mother during pregnancy and for her baby ( Castorina et al, 2015 ), while four successful pregnancies were described in MPS I women treated by bone marrow transplantation ( Rémerand et al, 2009 ). On the other hand, signs of precocious puberty were detected in some boys affected with MPS I and MPS III ( Milazzo et al, 2014 ) and MPS III A (Tylki-Szymanska & Metera).…”