oral contraceptives modify dna methylation and monocyte-derived macrophage function口服避孕药修改dna甲基化和monocyte-derived巨噬细胞的功能.pdf

Campesi et al. Biology of Sex Differences 2012, 3:4 /content/3/1/4 RESEARCH Open Access Oral contraceptives modify DNA methylation and monocyte-derived macrophage function 1,2* 1,2 3,4 1,4 5 6 Ilaria Campesi , Manuela Sanna , Angelo Zinellu , Ciriaco Carru , Laura Rubattu , Pamela Bulzomi , 7 8 9 10 6 1,2 Giuseppe Seghieri , Giancarlo Tonolo , Mario Palermo , Giuseppe Rosano , Maria Marino and Flavia Franconi Abstract Background: Fertile women may be encouraged to use contraception during clinical trials to avoid potential drug effects on fetuses. However, hormonal contraception interferes with pharmacokinetics and pharmacodynamics and modifies internal milieus. Macrophages depend on the milieu to which they are exposed. Therefore, we assessed whether macrophage function would be affected by the use of combined oral contraceptives (OCs) and if this influence depended on the androgenic or non-androgenic properties of progestin. Methods: Healthy adult women were enrolled and stratified into two groups: women who did not use OCs (Fs) and women treated with OCs (FOCs). FOCs were further stratified as a function of androgenic (FOCA+) and non- androgenic (FOCA-) properties of progestins. Routine hematological, biochemical, inflammatory and endothelial dysfunction parameters were measured. Monocyte-derived macrophages (MDMs) were evaluated for the expression and activity of estrogen receptors and androgen receptors, and release of tumor necrosis factor a (TNFa) was measured from unstimulated and lipopolysaccharide-stimulat