Effect of DHEA and metformin on corpus luteum in mice

Abstract

We evaluated the effect of hyperandrogenism in ovaries with functional and regressing corpora lutea (CL) and the action of metformin in preventing these possible alterations using a mouse model. To obtain a CL functional for 9G1 days, immature female mice of the BALB/c strain were injected i.p. with 10 IU/mouse of pregnant mare's serum gonadotropin (PMSG). DHEA (60 mg/kg body weight s.c., 24 and 48 h prior to kill) decreased both serum progesterone (P) and estradiol (E 2 ) levels and increased the activity of superoxide dismutase (SOD) from ovaries with functional CL (on day 5 after PMSG). It increased P and E 2 and the activities of SOD and catalase (CAT) and decreased lipoperoxidation of ovaries with regressing CL (on day 9 after PMSG). Treatment with DHEA did not affect the production of prostaglandin F 2a (PGF 2a ) or PGE by ovaries with functional CL, whereas DHEA decreased PGF 2a and increased PGE production by ovaries with regressing CL. Metformin (50 mg/kg body weight, orally) given together with DHEA restored E 2 levels from mice with ovaries with functional CL and serum P, PGF 2a and PGE levels, and oxidative balance in mice with ovaries with regressing CL. Metformin alone was able to modulate serum P and E 2 levels, lipoperoxidation, SOD and CAT, and the 5,5-dimethyl-1-pyrroline N-oxide/ % OH signal. These findings suggest that hyperandrogenism is able to induce or to rescue CL from luteolysis and metformin treatment is able to prevent these effects.

Prenatal Hyperandrogenization Induces Metabolic and Endocrine Alterations Which Depend on the Levels of Testosterone Exposure

“…We found that neither lipid peroxidation nor NO synthase activity was modified and GSH content was increased by prenatal hyperandrogenization. In agreement with previous findings [68]–[72], these data could suggest that a “controlled response”, given by the increase of the anti-oxidant metabolite GSH, could avoid the accumulation of ROS resulting in a no modification of lipid peroxidation index. The fact that prenatal hyperandrogenization did not modify the production of ovarian NO levels could suggest that that condition did not generate the accumulation of RNOS.…”

Peroxisome proliferator-activated receptor gamma and early folliculogenesis during an acute hyperandrogenism condition

“…As we have described during the periovulatory period (5,16,18) and the luteal phase (35), acute hyperandrogenism decreases serum P levels to those of controls. The process of steroidogenesis requires the active delivery of the substrate cholesterol (36)(37)(38)(39), and then, as we expected, the stimulation of steroidogenesis by eCG treatment was mediated by an increase in both the protein and mRNA expression of StAR in antral follicles.…”

Performing Vaginal Lavage, Crystal Violet Staining, and Vaginal Cytological Evaluation for Mouse Estrous Cycle Staging Identification

“…Entry into metestrus coincides with a continuous rise in progesterone hormone levels 6 and corresponds to the beginning of human luteal phase 12 (Figure 2, Metestrus, left panel). As progesterone levels start to rise and there is a small surge in 17-β-estradiol levels in response to corpus luteum activation 6,13,14 (Figure 2, Metestrus, left panel). The cell types present in vaginal smears during this stage are fragmented, cornified epithelial cells and smaller darker stained leukocytes ( Figure 1F, Figure 2, Metestrus, right panel).…”