Alteration of Extracellular Matrix Components in the Anterior Pituitary Gland of Neonatal Rats Induced by a Maternal Bisphenol A Diet during Pregnancy

Int J Mol Sci. 2021 Nov 23;22(23):12667. doi: 10.3390/ijms222312667.

Abstract

The extracellular matrix (ECM) plays crucial roles in the anterior pituitary gland via the mechanism of cell-ECM interaction. Since bisphenol A (BPA), a well-known endocrine disruptor, can cross through the placenta from mother to fetus and bind with estrogen receptors, cell populations in the neonatal anterior pituitary gland could be the target cells affected by this chemical. The present study treated maternal rats with 5000 µg/kg body weight of BPA daily throughout the pregnancy period and then investigated the changes in ECM-producing cells, i.e., pericytes and folliculostellate (FS) cells, including their ECM production in the neonatal anterior pituitary at Day 1. We found that pericytes and their collagen synthesis reduced, consistent with the increase in the number of FS cells that expressed several ECM regulators-matrix metalloproteinase (MMP) 9 and the tissue inhibitors of metalloproteinase (TIMP) family. The relative MMP9/TIMP1 ratio was extremely high, indicating that the control of ECM homeostasis was unbalanced. Moreover, transmission electron microscopy showed the unorganized cell cluster in the BPA-treated group. This study revealed that although the mother received BPA at the "no observed adverse effect" level, alterations in ECM-producing cells as well as collagen and the related ECM balancing genes occurred in the neonatal anterior pituitary gland.

Keywords: anterior pituitary gland; bisphenol A; collagen; endocrine-disrupting chemicals; extracellular matrix; folliculostellate cell; matrix metalloproteinase; neonate; pericyte; tissue inhibitors of metalloproteinase.

MeSH terms

  • Animals
  • Animals, Newborn
  • Benzhydryl Compounds / adverse effects*
  • Cell Line
  • Collagen / metabolism
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Female
  • Homeostasis
  • Maternal Exposure / adverse effects*
  • Matrix Metalloproteinase 9 / metabolism*
  • Microscopy, Electron, Transmission
  • Pericytes / drug effects
  • Pericytes / metabolism
  • Phenols / adverse effects*
  • Pituitary Gland, Anterior / drug effects*
  • Pituitary Gland, Anterior / metabolism
  • Pregnancy
  • Rats
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism*
  • Up-Regulation

Substances

  • Benzhydryl Compounds
  • Phenols
  • TIMP1 protein, rat
  • Tissue Inhibitor of Metalloproteinase-1
  • Collagen
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat
  • bisphenol A