Investigation of the Effect of Hormonal Therapy on Lupus Pathology and Reproductive System Damages in a Pristane‐Induced Mouse Model of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is an example of an autoimmune disease manifesting itself in an aberrated immune response directed against nuclear, cytoplasmic and cell-surface antigens. Among patients, symptoms are frequently intensified in females during their active reproductive years, pinpointing the interaction between reproductive and immune systems. Hence, it is urgent to address the question of how SLE can influence female fertility and the impact of hormones on disease manifestation. Mouse models of SLE are suitable tools for studying in detail the interactions of different systems and the impact of lupus development on the process of oogenesis. Lupus-like symptoms were induced through intraperitoneal injection of hydrocarbon oil pristane in healthy Balb/C mice. A short protocol for hormonal stimulation of humans was adapted for mice. Methods used to follow the immune status of the experimental animals were flow cytometry, ELISpot and ELISA, while the variety of autoantibodies, histology and quality of oocytes were characterised using fluorescent microscopy. A single i.p. injection of pristane induced production of autoantibodies and proteinuria, depositions of IgG-containing immune complexes in the kidneys and ovaries, increased the percentage of pro-inflammatory immune cell subtypes, and the number of plasmacytes secreting anti-dsDNA IgG antibodies. The hormonal stimulation of lupus mice altered ANA immunofluorescence imaging patterns, increased the total number and the percentage of well-developed oocytes, increased glomerular atrophy, and decreased mesangial proliferation in the kidneys. The exhibited impairments of oocytes in lupus mice provide evidence for a disturbed local microenvironment as a result of altered disease course.