Table I.

Sex related differences in pathogenesis of organ fibrosis

	Adult female	Adult female with reduced estrogen levels	Adult male
Kidney	H: Slower development of glomerulosclerosis38 A: Female rats produce lower amounts ROS in response to injury24 C: Competitive inhibitors of collagen protein synthesis on mesangial cells exhibited a greater response on females vs. male cells49	H: Become more susceptible to renal diseases after menopause17  A: E2 treatment of ovariectomized female rats prevented the aggravating renal damage24	H: Men progress to end stage renal disease (ESRD) faster than premenopausal women17 H: Had a greater degree of glomerular and tubular damage24 C: Mesangial cells inherently exhibit greater profibrotic and proinflammatory characteristics 42 A: Castration attenuated glomerulosclerosis in fatty male rats 28
Liver	H: Have slower progression of fibrosis and decreased incidence of cirrhosis pretransplantation44 A: Fibrotic response of the female liver to CCL4 was significantly weaker vs males46	A: Ovariectomy in the female model had a fibrogenic effect, inducing the hepatic expression of both types of procollagen and TIMP-148	H: Men are 2-fold more likely to die from chronic liver disease and cirrhosis vs women44 H: The fibrotic response of the male liver is significantly stronger vs females44
Lungs	A: Female rats may have an exaggerated response to lung injury relative to male rat54	A: Female rats have higher mortality rates and more severe fibrosis vs male54	A: Idiopathic pulmonary fibrosis, incidence is higher in males50,116 H, A: mRNA levels of ERα) were selectively upregulated in lung tissue and cultured myofibroblasts from male IPF patients as well as in male mice treated with bleomycin57
Heart	H: Women demonstrated more LV hypertrophy than men with less fibrosis61 C: Female rat cardiac fibroblasts, treatment with estradiol (10–8M) led to a significant downregulation of basal collagen I and III expression114	H: Women show greater aggravation of fibrosis in atrial fibrillation (ages 55–60)63 A: Advancing age and female gender were associated with increases in vascular and ventricular systolic and diastolic stiffness75 A: In a rat model of aging with ovariectomy, GPER activation was able to mitigate adverse LV remodeling and interstitial fibrosis104,109	H: Men greater endocardial fibrosis and stiffness61 A: Gene expression profiling also revealed that male hearts had a stronger induction of ECM-related genes and a stronger repression of mitochondrial genes85 C: Using cardiomyocyte specific GPER KO mice, males show greater adverse alterations in cardiac structure and impaired systolic and diastolic function vs. KO’s females111

Abbreviations: A, Animal, C, Cells; H, Human.