Endocrine Abstracts

Introduction: Systemic sclerosis (SSc) is a connective tissue disorder with higher prevalence in females which is characterized by vascular damage, pulmonary hypertension, inflammation and progressive fibrosis of skin and other internal organs such as lung. In the skin it has been shown that dermal adipose tissue atrophy and microangiopathy drive fibrosis development, however which is the underlying mechanism and whether this mechanism is responsible for the female prevalence of the diseases needs to be investigated. Here, we addressed these questions by using fra-2 over-expressing mice as a model of SSc.

Material and Methods: Female and male fra-2 overexpressing mice and wild type littermates were characterized at the age of 16-20 weeks. Ovariectomy was performed at the age of 6-8 weeks and the phenotype was analysed at 20 weeks of age. Lung function was measured using Flexivent system (SCIREQ), immunohistochemical staining for alpha-smooth muscle actin (αSMA) and von Willebrand factor (vWF) was performed to assess vascular remodelling. Inflammatory cell count was performed on bronchioalveolar lavage (BAL) of the mice and the right ventricular systolic pressure was acquired by closed chest hemodynamic measurement.

Results: Characterization of fra-2 over-expressing mice, showed that female transgenic mice have a worse phenotype compared to male, suggesting an influence of sex steroid hormones in the development of the phenotype. Female fra-2 over-expressing mice had worse lung function, higher inflammation and stronger vascular remodelling compared to male, however no differences in right ventricular systolic pressure was detected. Ovariectomy did not influence the phenotype, suggesting that female steroid hormones do not play a role in disease development and progression.

Conclusion: Female fra-2 over-expressing mice develop a more severe phenotype compared to male mice. Which is not influenced by ovariectomy. Further analyses are necessary to elucidate the male steroid hormones contribution to the phenotype of fra-2 over-expressing mice. Additionally, the underlying mechanism, the contribution and regulation of hormonal imbalance in these mice will be elucidated.