Subclinical hypothyroidism in gravide albino oxford rats cause delayed osteogenic differentiation in newborns

Abstract

Thyroid hormones (TH) are indispensable for normal development in mammals. The effects of maternal hypothyroidism on development and function of different organs of their offspring are well known. It is unclear how its subclinical form affects some of these processes, including endochondral ossification during the prenatal and early postnatal development. The aim of the study was to assess bone formation by defining the expression of tartarate-resistant acid phosphatase (TRAP), alkaline phosphatase (ALP) and mRNA for dentin matrix acidic phosphoprotein (DMP1) in tibia of pups from subclinical hypothyroid dams in early postnatal development. Subclinical hypothyroidism (SHT) was induced with propylthiouracil through drinking water (1.5 mg/l) in pregnant Albino Oxford dams from the first day of gravidity and during lactation. Control group was untreated. Five seven-day-old pups from each experimental group were euthanized. All histological examinations were performed on paraffin sections of the proximal tibial growth plate. Histochemistry was used to assess the expression of TRAP, immunohistochemistry for ALP and in situ hybridization for DMP1. The area of TRAP positive signal per 1µm2 and optical density of ALP immunostaining were evaluated using the Image J. The number of DMP1 positive cells was counted for given area using the same software. Level of thyroxine (T4) and triiodothyronine (T3) of dams and pups were decreased (data published). Expression of TRAP and ALP in the proximal tibial growth plate were lower in hypothyroid pups and the number of cells expressing mRNA for DMP1 was decreased. As it is known DMP1 and ALP are expressed in osteoblasts with an important role in endochondral ossification while TRAP represents a marker of osteoclasts function and bone resorption, so we can conclude that maternal SHT in rats leads to delayed osteogenic differentiation and compromised cartilage to bone transition in early infantile period.