Hyperandrogenization induces ovarian oxidative stress in pregnant Balb/c mice

MOTTA AB; LUCHETTI CG; ELÍA E; SOLANO, ME; SANDER V

Miami

Congreso; The Interamerican Society of Hypertension and the Consortium for Southeastern Hipertensión Control Joint Scientific Sessions; 2007

The Interamerican Society of Hypertension and the Consortium for Southeastern Hipertensión Control

Polycystic Ovary Syndrome (PCOS) is a reproductive disorder associated to hyperandrogenism, anovulation, diabetes, metabolic syndrome and cardiovascular risk as a consequence of the oxidative stress. Even when women with PCOS become pregnant, abortion is frequent. Metformin (M) is an insulin-sensitizing agent used in the treatment of diabetes and PCOS, but clinical practice is ahead of knowledge. The present study was directed to investigate aspects of M actions related to oxidative stress, glucose (G) and insulin (I) levels and steroidogenesis in preventing embryo resorption (ER) of hyperandrogenized early pregnant Balb/c mice. Pregnant mice were injected 24 and 48 h following implantation with one of the main elevated androgen in women with PCOS, dehydroepiandrosterone (DHEA: 6mg/100gr body weight: D Group). A second group received D+M (M: 50 mg/kg body weight oral per canulla) and a third only vehicle (control group C), n=20 mice per group. Animals from D showed 88+1% of ER while those from C and D+M group 43+3 and 35+5 % respectively. These data correlated with diminished both, serum progesterone (P) (D: 5+1 vs C:10+2 ng/ml) and estradiol (E) levels (D:218+40 vs C:518+143 pg/ml) while M prevented these effects: D+M:9+2 ng/ml for P and 621+98 pg/ml for E.  Hyperandrogenism increased both G and I levels (G; D: 175+19 vs  C: 124+6 mg mg/100 ml serum  and I; D:33+9 vs C:15+8 pg/ml serum) while M prevented these both effects (D+M: 134+20 mg/100 ml serum for G and D+M:25+2 pg/ml for I). Respect to uterine oxidative stress we found that malondialdehyde (MDA) the principal product of oxidation was increased by D (D:4+0.8 nmol MDA/mg protein vs C:2.6+0.6 nmol MDA/mg protein)  but M prevented it  (D+M: 2.5+0.6 nmol MDA/mg protein). In addition a dimition in the uterine glutathione (GSH) concentration (by spectrophotometric method) and catalase activity (CAT, by the consumption of hydrogen peroxide) was found; GSH, D:3.8+1.8 vs C:7.7+2.1 nM/mg protein and CAT; D:0.25+0.04 vs C: 0.5+0.003pmol/mg protein). Both effects were absents when M was administered together with D (D+M:6.2+1 nM/mg protein for GSH and 0.42+0.004 pmol/mg protein) data presented here allow concluding that M protects hyperandrogenized mice from ER restoring steroidogenesis and G and I levels and modulating uterine oxidative stress increased after D treatment and could be one of the aspects involved in the efficacy of this biguanide  in protecting against elevated androgens. These data are the first evidence that, as in other systems, M could act as a scavenger of reactive oxygen species produced in uterine tissue after hyperandrogenization..