Mouse minipuberty coincides with gonocyte transformation into spermatogonial stem cells: a model for human minipuberty
Ruili Li A B E , Amanda Vannitamby A , Sarah S. K. Yue A , David Handelsman C and John Hutson A B D
+ Author Affiliations
- Author Affiliations
A F Douglas Stephens Surgical Research Group, Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, Vic. 3052, Australia.
B Department of Paediatrics, University of Melbourne, Royal Children’s Hospital, Parkville, Vic. 3052, Australia.
C Andrology Laboratory, ANZAC Research Institute Concord Hospital, University of Sydney, NSW 2139, Australia.
D Department of Urology, Royal Children’s Hospital, Royal Children’s Hospital, Parkville, Vic. 3052, Australia.
E Corresponding author. Email: ruili.li@mcri.edu.au
Reproduction, Fertility and Development 29(12) 2430-2436 https://doi.org/10.1071/RD17100
Submitted: 22 November 2016 Accepted: 27 April 2017 Published: 23 May 2017
Abstract
As the transient postnatal hormone surge in humans, known as ‘minipuberty’, occurs simultaneously with key steps in germ-cell development, we investigated whether similar changes occur in the hypothalamic–pituitary–testicular axis of neonatal mice at a time that would coincide with gonocyte transformation into spermatogonial stem cells (SSC). Serum and testes were collected from C57Bl/6 mice at embryonic Day 17 (E17), birth (postnatal Day 0; P0) and daily until P10. Serum FSH and testosterone levels in both serum and testes were analysed and gene expression of FSH receptor (Fshr), luteinising hormone receptor (Lhr), anti-Müllerian hormone (Amh), octamer-binding transcription factor 4 (Oct-4), membrane type 1 metalloprotease (Mt1-mmp), proto-oncogene C-kit and promyelocytic leukaemia zinc finger (Plzf ) was quantified by real-time polymerase chain reaction. We found a transient surge of serum and testicular testosterone levels between P1 and P3 and a gradual increase in FSH from P1 to P10. Testis Lhr expression remained low from P0 until P10 but Fshr expression peaked between P3 and P6 (P < 0.01). The same was found for Oct-4 expression (a gonocyte marker), which surged between P3 and P6 (P < 0.01). Mt1-mmp expression peaked at P3 (P < 0.05). The expression pattern of both C-kit and Plzf (SSC markers) was similar with a steady increase from P1 to P10. These results show a transient activation of the hypothalamic–pituitary–testicular axis postnatally with increases in serum and testicular testosterone at P1–P3 and testicular Fshr (but not Lhr) at P3–P6. These changes coincide with increases in gene expression of Oct4, Mt1-mmp, Plzf and C-kit, reflecting gonocyte activation, migration and transformation into SSC. In conclusion, these findings suggest that ‘minipuberty’ does occur in mice and that gonocyte transformation may be driven by a transient FSH signalling pathway.
Additional keywords: gene expression, germ cells, spermatogonia, testis.
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