Testosterone-retinoic acid signaling directs spermatogonial differentiation and seasonal spermatogenesis in the Plateau pika (Ochotona curzoniae)

Theriogenology. 2019 Jan 1:123:74-82. doi: 10.1016/j.theriogenology.2018.09.033. Epub 2018 Sep 29.

Abstract

During evolution, animals optimize their reproductive strategies to increase offspring survival. Seasonal breeders reproduce only during certain times of the year. In mammals, reproduction is tightly controlled by hypothalamus-pituitary-gonad axis. Although pathways regulating gametogenesis in non-seasonal model species have been well established, molecular insights into seasonal reproduction are severely limited. Using the Plateau pika (Ochotona curzoniae), a small rodent animal species native to the Qinghai-Tibetan plateau, as a model, here we report that seasonal spermatogenesis is governed at the level of spermatogonial differentiation. In testis of the reproductively dormant animals, undifferentiated spermatogonia failed to differentiate and accumulated in the seminiferous tubules. RNA-seq analyses of the active and dormant testes revealed that genes modulating retinoic acid biogenesis and steriodogenesis were differentially regulated. A single injection of all-trans retinoic acid (ATRA) reinitiated spermatogenesis and inhibition the function of RA-degrading enzyme CYP26B1 for 10 days induced spermatogonial differentiation. Strikingly, testosterone injection reinitiated spermatogenesis in short day adapted animals. Testosterone provides a permissive environment of RA biogenesis and actions in testis, therefore, indirectly controls spermatogonial differentiation. Collectively, these findings provide a key mechanistic insight regarding the molecular regulation of seasonal reproduction in mammals.

Keywords: Melatonin; Retinoic acid; Seasonal reproduction; Spermatogenesis; Testosterone.

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Lagomorpha / physiology*
  • Male
  • Retinoic Acid 4-Hydroxylase / metabolism
  • Seasons
  • Signal Transduction / physiology*
  • Spermatogonia / physiology*
  • Testosterone / physiology*
  • Tretinoin / administration & dosage
  • Tretinoin / pharmacology*
  • Tretinoin / physiology

Substances

  • Testosterone
  • Tretinoin
  • Retinoic Acid 4-Hydroxylase