Leukemia Inhibitory Factor-Receptor is Dispensable for Prenatal Testis Development but is Required in Sertoli cells for Normal Spermatogenesis in Mice

Michael Curley, Laura Milne, Sarah Smith, Nina Atanassova, Diane Rebourcet, Annalucia Darbey, Patrick W. F. Hadoke, Sara Wells, Lee B. Smith*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Leukemia inhibitory factor (LIF), a pleiotropic cytokine belonging to the interleukin-6 family, is most often noted for its role in maintaining the balance between stem cell proliferation and differentiation. In rodents, LIF is expressed in both the fetal and adult testis; with the peritubular myoid (PTM) cells thought to be the main site of production. Given their anatomical location, LIF produced by PTM cells may act both on intratubular and interstitial cells to influence spermatogenesis and steroidogenesis respectively. Indeed, the leukemia inhibitory factor receptor (LIFR) is expressed in germ cells, Sertoli cells, Leydig cells, PTM cells and testicular macrophages, suggesting that LIF signalling via LIFR may be a key paracrine regulator of testicular function. However, a precise role(s) for testicular LIFRsignalling in vivo has not been established. To this end, we generated and characterised the testicular phenotype of mice lacking LIFR either in germ cells, Sertoli cells or both, to identify a role for LIFRsignalling in testicular development/ function. Our analyses reveal that LIFR is dispensable in germ cells for normal spermatogenesis. However, Sertoli cell LIFR ablation results in a degenerative phenotype, characterised by abnormal germ cell loss, sperm stasis, seminiferous tubule distention and subsequent atrophy of the seminiferous tubules.

Original languageEnglish
Article number11532
Number of pages13
JournalScientific Reports
Volume8
DOIs
Publication statusPublished - 1 Aug 2018

Keywords

  • CRE RECOMBINASE ACTIVITY
  • MALE REPRODUCTIVE-SYSTEM
  • IL-6 SIGNAL TRANSDUCER
  • ANDROGEN RECEPTOR
  • LEYDIG-CELLS
  • TRANSGENIC MICE
  • LIF RECEPTOR
  • RAT SERTOLI
  • GERM-CELLS
  • GP130

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