Impact of prenatal hypoxia on fetal bone growth and osteoporosis in ovariectomized offspring rats

Reprod Toxicol. 2018 Jun:78:1-8. doi: 10.1016/j.reprotox.2018.02.010. Epub 2018 Mar 7.

Abstract

Prenatal hypoxia causes intrauterine growth retardation. It is unclear whether/how hypoxia affects the bone in fetal and offspring life. This study showed that prenatal hypoxia retarded fetal skeletal growth in rats, inhibited extracellular matrix (ECM) synthesis and down-regulated of insulin-like growth factor 1 (IGF1) signaling in fetal growth plate chondrocytes in vivo and in vitro. In addition, ovariectomized (OVX) was used for study of postmenopausal osteoporosis. Compared with the control, OVX offspring in prenatal hypoxic group showed an enhanced osteoporosis in the femurs, associated with reduced proteoglycan and IGF1 signaling. The results indicated prenatal hypoxia not only delayed fetal skeletal growth, but also increased OVX-induced osteoporosis in the elder offspring probably through down-regulated IGF1 signaling and inhibition of ECM synthesis, providing important information of prenatal hypoxia on functional and molecular bone growth and metabolism in fetal and offspring.

Keywords: Offspring; Osteoporosis; Prenatal hypoxia; Skeletal growth retardation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Development*
  • Extracellular Matrix / metabolism
  • Female
  • Femur / embryology
  • Femur / metabolism
  • Fetal Development*
  • Growth Plate / embryology
  • Growth Plate / metabolism
  • Hypoxia / complications*
  • Insulin-Like Growth Factor I / metabolism
  • Osteoporosis*
  • Ovariectomy
  • Pregnancy
  • Rats, Sprague-Dawley
  • Receptors, Somatomedin / metabolism
  • Signal Transduction

Substances

  • Receptors, Somatomedin
  • insulin-like growth factor-1, rat
  • Insulin-Like Growth Factor I