Heat Stress Alters Ovarian Insulin-Mediated Phosphatidylinositol-3 Kinase and Steroidogenic Signaling in Gilt Ovaries.
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.
Department of Animal Science, Iowa State University, Ames, Iowa.
Jackson
J
Nteeba
Department of Animal Science, Iowa State University, Ames, Iowa.
M Victoria
MV
Sanz-Fernandez
Department of Animal and Poultry Sciences, Virginia Tech University, Blacksburg, Virginia.
Robert P
RP
Rhoads
Department of Animal Science, Iowa State University, Ames, Iowa.
Lance H
LH
Baumgard
Department of Animal Science, Iowa State University, Ames, Iowa.
Jason W
JW
Ross
Department of Animal Science, Iowa State University, Ames, Iowa akeating@iastate.edu.
Aileen F
AF
Keating
D000818:Animals; D005260:Female; D006358:Hot Temperature; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D010053:Ovary / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological / Q000502:physiology*; D013552:Swine; D000098682:Steroidogenic Acute Regulatory Protein
D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D058539:Phosphatidylinositol 3-Kinase; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt
hyperinsulinemia; hyperthermia; infertility; ovary