Urology
Postnatal germ cell development during first 18 months of life in testes from boys with non-syndromic cryptorchidism and complete or partial androgen insensitivity syndrome

https://doi.org/10.1016/j.jpedsurg.2018.12.011Get rights and content

Abstract

Introduction

Neonatal testicular germ cells/gonocytes, transform into stem cells for spermatogenesis during ‘minipuberty’, driving change in timing of surgery. This study examined gonocyte transformation in cryptorchid testes in children ≤ 18 months of age with unilateral, bilateral undescended testes (UDT), complete or partial androgen insensitivity syndrome (CAIS, PAIS) [3,4].

Material and methods

Testicular biopsies were taken from patients with unilateral or bilateral UDT, PAIS or CAIS, aged 10 days–18 months. These testicular sections underwent immunohistochemistry with antibodies (Oct4, Ki67, C-Kit, Sox9) followed by confocal imaging, cell counting and statistical analysis.

Results

Both Sertoli cells/tubule and germ cells (GC)/tubule decreased with age, and % empty tubules (no GC) increased with age but with no significant differences between patient groups. Oct4+ germ cells/tubule decreased with age. There are some GCs and Sertoli cells proliferating during the first year and most proliferating Oct4+ germ cells (Oct4+/Ki67+) were located off tubular basement membrane.

Conclusion

Our study showed that Oct4 expression gradually decreased after minipuberty and transformation into spermatogonia. Germ cells and Sertoli cells undergo mitosis during the first 12 months although not abundantly. We propose that Oct4+ gonocyte transformation into spermatogonia via proliferation and migration to the basement membrane may be delayed in UDT.

Section snippets

Patients and specimens

Total of 42 testicular biopsies from 35 non-syndromic patients with unilateral UDT (n = 16), bilateral UDT (n = 19), and partial or complete androgen insensitivity (PAIS, n = 2 or CAIS, n = 5) from 10 days to 18 months of age were used for the study. Testis position for all UDT samples were either inguinal or the external inguinal ring, CAIS were 4 inguinal and 1 abdominal, PAIS were labioscrotal. The UDT specimens were fixed in Stieve's fixative at the time of orchidopexy in, Denmark (ethics

Results

Sox9 labeled the nuclei of all Sertoli cells, therefore, unstained cells (Sox9) in testicular tubules were clearly distinguished as germ cells. The number of Sertoli cells per tubule showed a decreasing trend with increase of age (Fig. 1A) and the number of germ cells per tubule showed a sharp decrease with increasing of age (Fig. 1B), whereas the percentage of empty tubules (tubules without germ cells) was increased with age (Fig. 1C) for unilateral, bilateral and CAIS UDT, however, there was

Discussion

During the first 18 months of age, in children with unilateral and bilateral UDT the number of both Sertoli cells and germ cells per tubule were found to be decreasing and the percentage of empty tubules was increased with age. A similar trend was observed in children with CAIS/PAIS. These results are similar to previous findings [9], [12]. The number of germ cells per tubule from CAIS testes was significantly higher than unilateral and bilateral UDT (Fig. 1D). This may be due to a lack of

Conflict of interest

The authors declare that they have no conflicts of interest.

Acknowledgement

We sincerely thank Dr. Angela Pezic at Molecular Epidemiology, Murdoch Children's Research Institute for help on the linear regression analysis.

This study was supported by the Australian National Health and Medical Research Council (Grant Number APP1144752) and the Victorian Government's Operational Infrastructure Support Programme.

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