Lightning Talk + Poster ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Interferon epsilon regulates testosterone production in the adult mouse testis (#418)

Rukmali Wijayarathna 1 2 , Linden J Gearing 2 3 , Paul J Hertzog 2 3 , Mark Hedger 2 4
  1. Centre For Reproductive Health, Hudson Institute of Medical Research, Melbourne, Victoria, Australia
  2. Dept. of Molecular and Translational Sciences, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia
  3. Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Melbourne, Victoria, Australia
  4. Centre For Reproductive Health, Hudson Institute of Medical Research, Melbourne, Victoria, Australia

Interferon epsilon (IFNɛ) is a type I interferon originally discovered in female reproductive epithelia for its antiviral and antiproliferative properties. We recently demonstrated that IFNɛ is constitutively expressed by macrophages, Leydig cells, and meiotic and post-meiotic spermatogenic cells in the murine and human testis, and plays a protective anti-viral role in the murine male reproductive tract. Significantly, expression of IFNɛ  in the testis emerged between day 20 and 25 of age in mice, indicating a specific role in sexually-mature males. Consequently, the role of IFNɛ in testicular steroidogenesis was examined.

The gross anatomy and histology of the testis, epididymis and seminal vesicles of adult (56 day-old) and juvenile (25 day-old) mice lacking IFNɛ (Ifne-/-) was compared to normal wild-type mice. Luteinising hormone (LH) and testosterone were measured in serum and testis extracts from adult mice by RIA. RNA-sequencing (RNAseq) was performed on whole-testis RNA from adult Ifne -/-mice and wild-type littermates.

Testicular, epididymal and seminal vesicle weights in Ifne-/-mice were not different from wild-type controls at 25 and 56 days of age, and no gross histological differences in Leydig cell morphology was observed. However, adult Ifne -/-mice displayed an approximately 50% reduction in serum testosterone compared to wild-type mice. Serum LH and intratesticular testosterone were not significantly altered. RNAseq analysis of adult Ifne-/-and wild-type mouse testes showed reduced expression of the key testicular steroidogenic genes, Cyp11a1, Cyp17a1 and Star. Cyp19a and Hsd3b1 were unaltered.

These data demonstrate a significant role for constitutive IFNɛ in supporting normal serum testosterone levels in adult mice, apparently by stimulating expression of the genes responsible for cholesterol mobilisation (Star), side-chain cleavage (Cyp11a1) and conversion of pregnenolone/progesterone into androgens (Cyp17a1). However, intratesticular testosterone, serum LH and seminal vesicle weights were not altered in mice lacking IFNɛ, and the precise mechanisms involved require further investigation.