The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

What is the role of the testis in regulating epididymal activin levels? (#314)

Rukmali Wijayarathna 1 , Rosemary Genovese 1 , Andreas Meinhardt 1 2 , Kate A Loveland 1 3 , Barry Hinton 4 , Mark P Hedger 1 3
  1. Hudson Institute of Medical Research, Clayton, VIC, Australia
  2. Department of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany
  3. Molecular and Translational Sciences, School of Clinical Sciences, Monash University, Clayton, VIC, Australia
  4. School of Medicine, University of Virginia, Charlottesville, Virginia, USA

Activins are homodimeric cytokines that regulate testicular and epididymal function. Activin A and B are encoded by the inhibin β-subunit genes, Inhba and Inhbb, respectively. Both activins are preferentially expressed in the caput epididymis. Activin action is opposed by inhibin in the testis, and by follistatin in the vas deferens, but the factors that control epididymal activin production are unknown. The potential role of the testis in this regulation was investigated.

Mice lacking the inhibin α-subunit (Inha-/-), which cannot produce inhibin, have increased intratesticular activin A (34-fold) and activin B (38-fold), and increased testicular expression of Inhba (750-fold) and Inhbb (7-fold); however, activin A and B protein and mRNA levels were not different from wildtype in the epididymides of the Inha-/- mice. These data suggest that the testis is not a significant source of epididymal activins, and that inhibin is not involved in their regulation.

The efferent ducts connecting the testis to the caput epididymis in 10 week old C57/Bl6 mice were ligated (EDL) bilaterally, or unilaterally. Efferent ducts were manipulated, but not ligated, on the contralateral side as controls. Tissues were collected 7 days post-surgery. The seminiferous epithelium was disrupted in ligated testes, but control testes appeared normal. Inhba and Inhbb were significantly increased in the caput of bilateral EDL mice (2- and 6-fold, respectively), but not in the ligated or control caput of unilateral EDL mice. The gene encoding indoleamine-2,3-dioxygenase (Ido1), an immunoregulatory gene postulated to be regulated by activins in the epididymis, increased 60-fold in the bilateral EDL epididymis, but not in unilateral EDL mice.

These data suggest that caput epididymal expression of Inhba, Inhbb and Ido1 are not acutely regulated by sperm or testicular lumicrine secretions. However, it appears that the testis influences the expression of these genes via a systemic, possibly endocrine or immunological, mechanism.