Bone Status in a Mouse Model of Experimental Autoimmune-Orchitis

Int J Mol Sci. 2021 Jul 23;22(15):7858. doi: 10.3390/ijms22157858.

Abstract

Investigations in male patients with fertility disorders revealed a greater risk of osteoporosis. The rodent model of experimental autoimmune-orchitis (EAO) was established to analyze the underlying mechanisms of male infertility and causes of reduced testosterone concentration. Hence, we investigated the impact of testicular dysfunction in EAO on bone status. Male mice were immunized with testicular homogenate in adjuvant to induce EAO (n = 5). Age-matched mice were treated with adjuvant alone (adjuvant, n = 6) or remained untreated (control, n = 7). Fifty days after the first immunization specimens were harvested. Real-time reverse transcription-PCR indicated decreased bone metabolism by alkaline phosphatase and Cathepsin K as well as remodeling of cell-contacts by Connexin-43. Micro computed tomography demonstrated a loss of bone mass and mineralization. These findings were supported by histomorphometric results. Additionally, biomechanical properties of femora in a three-point bending test were significantly altered. In summary, the present study illustrates the induction of osteoporosis in the investigated mouse model. However, results suggest that the major effects on bone status were mainly caused by the complete Freund's adjuvant rather than the autoimmune-orchitis itself. Therefore, the benefit of the EAO model to transfer laboratory findings regarding bone metabolism in context with orchitis into a clinical application is limited.

Keywords: biomechanical properties; experimental autoimmune-orchitis; micro-CT; mouse model; osteocalcin; osteoporosis; testosterone.

MeSH terms

  • Animals
  • Autoimmune Diseases / complications*
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / pathology
  • Autoimmune Diseases / physiopathology
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / metabolism*
  • Bone and Bones / pathology
  • Bone and Bones / physiopathology
  • Disease Models, Animal
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Orchitis / complications*
  • Orchitis / metabolism
  • Orchitis / pathology
  • Orchitis / physiopathology
  • Osteoporosis / diagnostic imaging
  • Osteoporosis / immunology*
  • X-Ray Microtomography