Aburto-Hernández Cynthia, Barrera David, Ortiz-Hernández Rosario, Espinoza-Simón Emilio, Parra-Gámez Leticia, González James, Escobar M Luisa, Vázquez-Nin Gerardo H, Echeverría-Martínez Olga, Torres-Ramírez Nayeli
Departamento de Biología Celular, Facultad de Ciencias, Universidad Nacional Autónoma de Mexico, Avenida Universidad 3000, Cd. Universitaria, Coyoacán, Mexico City 04510, Mexico.
Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Av. Vasco de Quiroga No. 15, Col. Belisario Domínguez, Sección XVI, Mexico City 14080, Mexico.
Metabolites. 2022 Nov 26;12(12):1182. doi: 10.3390/metabo12121182.
Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder of unknown etiology. Hyperandrogenism (HA) is the main diagnostic criteria for PCOS, in addition to being a risk factor for developing several disorders throughout the patient's life, including pregnancy. However, the impact on offspring is little known. Therefore, the aim of this work was to evaluate the effect of maternal HA on glucose metabolism and hepatic lipid accumulation in adult offspring. We used Balb/c mice treated with dehydroepiandrosterone (DHEA) for 20 consecutive days. The ovary of DHEA-treated mice showed hemorrhagic bodies, an increased number of atretic follicles, and greater expression of genes related to meiotic cell cycle and DNA repair. The DHEA offspring (O-DHEA) had low birth weight, and some pups showed malformations. However, O-DHEA individuals gained weight rapidly, and the differences between them and the control group became significantly greater in adulthood. Moreover, O-DHEA presented higher serum glucose after a 6 h fast and a larger area under glucose, insulin, and pyruvate tolerance test curves. Oil Red O staining showed a more significant accumulation of fat in the liver but no changes in serum cholesterol and triacylglycerol levels. In summary, our results show that HA, induced by DHEA, affects gene expression in oocyte, which in turn generates defects in embryonic development, insulin resistance, and alteration in hepatic gluconeogenesis and lipid metabolism in O-DHEA, thereby increasing the risk of developing metabolic diseases.
多囊卵巢综合征（PCOS）是一种病因不明的内分泌代谢紊乱疾病。高雄激素血症（HA）是PCOS的主要诊断标准，此外，它还是患者一生中发生多种疾病（包括妊娠相关疾病）的危险因素。然而，其对后代的影响却鲜为人知。因此，本研究旨在评估母体HA对成年后代葡萄糖代谢和肝脏脂质蓄积的影响。我们使用连续20天接受脱氢表雄酮（DHEA）治疗的Balb/c小鼠。DHEA处理的小鼠卵巢出现出血性卵泡，闭锁卵泡数量增加，与减数分裂细胞周期和DNA修复相关的基因表达增强。DHEA后代（O-DHEA）出生体重低，部分幼崽出现畸形。然而，O-DHEA个体体重迅速增加，成年后与对照组的差异显著增大。此外，禁食6小时后，O-DHEA的血糖水平更高，葡萄糖、胰岛素和丙酮酸耐量试验曲线下面积更大。油红O染色显示肝脏中脂肪蓄积更明显，但血清胆固醇和三酰甘油水平无变化。总之，我们的结果表明，DHEA诱导的HA影响卵母细胞中的基因表达，进而导致O-DHEA胚胎发育缺陷、胰岛素抵抗以及肝脏糖异生和脂质代谢改变，从而增加患代谢性疾病的风险。
