Hyperandrogenization induces ovarian oxidative stress in pregnant Balb/c mice

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

Miami, Florida, USA

Congreso; Inter American Society of Hipertensión and Consortium for Southeastern Hipertensión control Joint Meeting; 2007

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

Polycystic Ovary Síndrome (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 the knowledge. The present study was directed to investigate aspects of M action 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 sc injected 24 and 48 h post implantation with one of the main elevated androgen present in women with PCOS, the dehydroepiandrosterone (D: 60 mg/kg body weight) a second group received D+M (M: 50 mg/kg BW oral per canula) and a third only vehicle (control group: C), n= 20 mice/group. Animals from D showed 88 + 1 % ER while those from C and D+M groups 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. Hyperandrogenization increased both G and I levels (G; D: 175+19 vs C: 124+6 mg/100 ml serum and I; D:33+9 vs C:15+8 pg/ml serum) while M prevented these both effects. Respect to ovarian oxidative stress we found that malondyaldehide (MDA), the principal product of the oxidation, was increased by D (D: 4+0.8 vs C: 2.6+0.6 nmol MDA/mg protein) but M prevented it. In addition a diminution in the ovarian 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 0.5+0.03 pmol/mg protein. Both effects were absent in the D+M group. Data presented here allow concluding that M protects hyperandrogenized mice of ER restoring steroidogenesis and G and I by modulating ovarian 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 scavenger of reactive species oxygen produced in ovarian tissue after hyperandrogenization.