Mouse minipuberty coincides with gonocyte transformation into spermatogonial stem cells: a model for human minipuberty

Reprod Fertil Dev. 2017 Nov;29(12):2430-2436. doi: 10.1071/RD17100.

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.

MeSH terms

  • Adult Germline Stem Cells / cytology*
  • Adult Germline Stem Cells / metabolism
  • Animals
  • Anti-Mullerian Hormone / genetics
  • Anti-Mullerian Hormone / metabolism
  • Follicle Stimulating Hormone / blood
  • Follicle Stimulating Hormone / metabolism*
  • Male
  • Mice
  • Models, Animal
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Proto-Oncogene Mas
  • Receptors, FSH / genetics
  • Receptors, FSH / metabolism
  • Receptors, LH / genetics
  • Receptors, LH / metabolism
  • Spermatogonia / cytology*
  • Spermatogonia / metabolism
  • Testis / cytology*
  • Testis / metabolism
  • Testosterone / blood
  • Testosterone / metabolism*

Substances

  • MAS1 protein, human
  • Octamer Transcription Factor-3
  • Proto-Oncogene Mas
  • Receptors, FSH
  • Receptors, LH
  • Testosterone
  • Anti-Mullerian Hormone
  • Follicle Stimulating Hormone