Alteration of extracellular matrix components in anterior pituitary gland of neonatal rats induced by maternal Bisphenol a (BPA) diet during pregnancy

Abstract

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical that is widely used in the resin and plastic manufacturing sectors. Prenatal exposure to this chemical results in changes of pituitary hormone-producing cells. However, there have been no reports of the alterations of extracellular matrix (ECM) which play a role in controlling cell activities in the pituitary gland. In the present study, a daily oral dose of 5,000 µg/kg BW of BPA was administered to pregnant rats. ECM-producing cells, i.e., pericytes and folliculostelate cells, ECM products, and ECM regulators were investigated in the neonatal anterior pituitary at day 1 at the histology and molecular levels. The number of cells and immunosignal intensity were determined under light microscopy. Real-time RT-qPCR was used to investigate the mRNA expression of the ECM products and their controllers. The ultrastructural changes were observed by transmission electron microscopy. In BPA-treated rats, pericytes and their collagen syntheses were reduced, consistent with the increase in the number of FS cells that expressed several ECM regulators. Components of the ECM regulators were also adaptable. MMP2, MMP9, and TIMPs (TIMP 1-4) mRNAs were upregulated. In addition, mRNA levels of decorin and osteoglycin were increased, whereas those of PRELP and Tsukiji were dropped. Moreover, transmission electron microscopy showed the unorganized-cell cluster in the gland. This study revealed that although mother received BPA at a no-observed-adverse-effect level, the alterations of ECM-producing cells as well as collagen and related ECM balancing genes occur in the neonatal anterior pituitary gland. Therefore, awareness of the harm from this chemical should be raised, especially during pregnancy.