Nteeba Jackson, Sanz-Fernandez M Victoria, Rhoads Robert P, Baumgard Lance H, Ross Jason W, Keating Aileen F
Department of Animal Science, Iowa State University, Ames, Iowa.
Department of Animal and Poultry Sciences, Virginia Tech University, Blacksburg, Virginia.
Biol Reprod. 2015 Jun;92(6):148. doi: 10.1095/biolreprod.114.126714. Epub 2015 Apr 29.
Heat stress (HS) compromises a variety of reproductive functions in several mammalian species. Inexplicably, HS animals are frequently hyperinsulinemic despite marked hyperthermia-induced hypophagia. Our objectives were to determine the effects of HS on insulin signaling and components essential to steroid biosynthesis in the pig ovary. Female pigs (35 ± 4 kg) were exposed to constant thermoneutral (20°C; 35%-50% humidity; n = 6) or HS conditions (35°C; 20%-35% humidity; n = 6) for either 7 (n = 10) or 35 days (n = 12). After 7 days, HS increased (P < 0.05) ovarian mRNA abundance of the insulin receptor (INSR), insulin receptor substrate 1 (IRS1), protein kinase B subunit 1 (AKT1), low-density lipoprotein receptor (LDLR), luteinizing hormone receptor (LHCGR), and aromatase (CYP19a). After 35 days, HS increased INSR, IRS1, AKT1, LDLR, LHCGR, CYP19a, and steroidogenic acute regulatory protein (STAR) ovarian mRNA abundance. In addition, after 35 days, HS increased ovarian phosphorylated IRS1 (pIRS1), phosphorylated AKT (pAKT), STAR, and CYP19a protein abundance. Immunostaining analysis revealed similar localization of INSR and pAKT1 in the cytoplasmic membrane and oocyte cytoplasm, respectively, of all stage follicles, and in theca and granulosa cells. Collectively, these results demonstrate that HS alters ovarian insulin-mediated PI3K signaling pathway members, which likely impacts follicle activation and viability. In summary, environmentally induced HS is an endocrine-disrupting exposure that modifies ovarian physiology and potentially compromises production of ovarian hormones essential for fertility and pregnancy maintenance.
热应激（HS）会损害多种哺乳动物的多种生殖功能。令人费解的是，尽管热应激导致明显的体温过高引起摄食减少，但热应激动物经常出现高胰岛素血症。我们的目标是确定热应激对猪卵巢中胰岛素信号传导以及类固醇生物合成所必需的成分的影响。将雌性猪（35±4千克）暴露于恒定的热中性环境（20°C；湿度35%-50%；n = 6）或热应激环境（35°C；湿度20%-35%；n = 6）中7天（n = 10）或35天（n = 12）。7天后，热应激使卵巢中胰岛素受体（INSR）、胰岛素受体底物1（IRS1）、蛋白激酶B亚基1（AKT1）、低密度脂蛋白受体（LDLR）、促黄体生成素受体（LHCGR）和芳香化酶（CYP19a）的mRNA丰度增加（P < 0.05）。35天后，热应激使INSR、IRS1、AKT1、LDLR、LHCGR、CYP19a和类固醇生成急性调节蛋白（STAR）的卵巢mRNA丰度增加。此外，35天后，热应激使卵巢中磷酸化IRS1（pIRS1）、磷酸化AKT（pAKT）、STAR和CYP19a的蛋白丰度增加。免疫染色分析显示，INSR和pAKT1分别在所有阶段卵泡的细胞质膜和卵母细胞细胞质中以及在卵泡膜细胞和颗粒细胞中具有相似的定位。总体而言，这些结果表明热应激会改变卵巢中胰岛素介导的PI3K信号通路成员，这可能会影响卵泡的激活和活力。总之，环境诱导的热应激是一种内分泌干扰暴露，会改变卵巢生理功能，并可能损害生育和维持妊娠所必需的卵巢激素的产生。
