Impact of maternal androgen excess and polycystic ovary syndrome on placental metabolic pathways

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 532-553-Hyperandrogenic Disorders
Basic/Clinical
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-551
Manuel Maliqueo*1, Inger Sundström Poromaa2, Eszter Vanky3, Helena Åkerud2, Solhild Stridsklev3, Miao Sun4, Thomas Jansson5 and Elisabet Stener-Victorin4
1University of Chile, Santiago, Chile, 2Uppsala University, Uppsala, Sweden, 3Norwegian University of Science and Technology, Trondheim, Norway, 4University of Gothenburg, Gothenburg, Sweden, 5University of Texas Health Science Center, San Antonio
Pregnant women with polycystic ovary syndrome (PCOS) have elevated androgen levels and an increased risk for pregnancy complications such as altered fetal growth. The mechanisms linking PCOS to fetal outcome are largely unknown but may involve placental dysfunction. Maternal androgen excess in rats decreases placental amino acids transfer and increases the expression of estrogen receptors (ER), androgen receptor (AR) and 17β-hydroxysteroid dehydrogenase-2 (17β-HSD2). Using a translational approach, we tested the hypothesis that high maternal androgens dysregulate steroid receptors, steroidogenic enzymes and metabolic pathways in placentas from women with PCOS and placentas from androgenized pregnant rats.

Experiment 1: Placental samples from 38 women with PCOS and 40 controls, who delivered between gestational week 34 and 42, were collected. The gene expression of steroid receptors (AR and ESR1), steroidogenic enzymes (CYP11A1, HSD3B1, CYP19A1, SRD5A2, AKR1C2, AKR1C3 and HSD11B1) and molecules related to metabolic pathways (ADIPOQ, ADIPOR1, ADIPOR2, IGF1, LEP, LEPR and SCL2A4) were analyzed by TaqMan© low-density array.

Experiment 2: Pregnant rats were daily injected (sc) with 5.0 mg of testosterone propionate (T-treated; n=8) or sesame oil (control; n=7) from GD15 until GD19. Placentas were collected on GD21 to measure total and phosphorylated protein expression of eukaryotic initiation factor 4E binding protein 1 (4E-BP1), S6 ribosomal protein and signal transducer and activator of transcription 3 (STAT-3) by western blot, which are known to regulate placental amino acid transporters.

Results: The placental mRNA expression of ESR1 (P = 0.015) and AKR1C3 (P = 0.023) were higher and CYP11A1 (P = 0.024), LEP (P = 0.005), LEPR (P = 0.023) and SCL2A4 (P < 0.001) were lower in women with PCOS compared to controls. These genes encode for ERα, 17β-HSD5, P450scc, leptin, leptin receptor and GLUT4, respectively. mTOR activity was unaltered in the placenta from T-treated rats. Total and phosphorylated STAT3, which is downstream of the leptin receptor, remain to be analyzed.

Conclusion: Increased placental expression of ERα and steroidogenic enzymes (17β-HSD2/5) were observed in women with PCOS similar to reported in androgenized pregnant rats. Moreover, our preliminary data suggest that placental leptin signaling is inhibited in PCOS. Because leptin stimulates placental amino acid transport, these changes could lead to altered transport of nutrients to the fetus.

Nothing to Disclose: MM, IS, EV, H, SS, MS, TJ, ES

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Marianne and Marcus Wallenberg foundation; Swedish Research Council Project No. K2012-55X-15276-08-3; The Jane and Dan Olsson Foundations; The Novo Nordisk Foundation; The Hjalmar Svensson Foundation; The Adlerbert Research Foundation; Wilhelm and Martina Lundgrens’s Science Fund; The Swedish Federal Government under the LUA/ALF agreement (ALFGBG-136481).