Effect of Subclinical and Overt Form of Rat Maternal Hypothyroidism on Offspring Endochondral Bone Formation

Abstract

Maternal hypothyroidism in its overt form affects skeletal development of the offspring, but these data are not available for the subclinical form which is becoming very frequent among pregnant women. We hypothesized that the subclinical form of hypothyroidism in rat dams, infl uences the process of offspring endochondral ossifi cation affecting proliferation and differentiation of chondrocytes, osteoclasts and osteoblasts in pups. Seven-day-old male pups (n=18) derived from control dams and dams treated with a low dose (1.5 mg/L) or high dose (150 mg/L) of propylthiouracil in drinking water during pregnancy and lactation were used. Histomorphometric analysis of pups’ tibia proximal growth plate, expression of mRNA, immunohistochemical and histochemical visualization of extracellular matrix components was performed. The length of the tibia was reduced in hypothyroid pups. Secretion of type 2 and 10 collagens in the subclinical and overt form were lower while the amount of glycosaminoglycans was higher when compared with controls. Down-regulated tartrate resistant acid phosphatase mRNA indicated altered osteoclasts function while lower expression of dentin matrix acid protein-1 mRNA and reduced synthesis of type 1 collagen accentuated a compromised bone formation in the overt form of hypothyroidism. The subclinical form of maternal hypothyroidism had a negative effect on the differentiation of hypertrophic chondrocytes and calcifi ed cartilage removal in 7-day-old pups. In addition, overt hypothyroidism had a negative effect on the proliferation of chondrocytes and deposition of osteoid. Both forms of hypothyroidism resulted in a decrease of tibia length due to changes in growth plate formation.

Radiological Investigation of Guinea Pig (Cavia porcellus) Lumbar Vertebral Morphology ‒ A Biomechanical Aspect

“…Regulation of bone growth is a complex process that depends on genetic factors, vascularization [17], the infl uence of hormones [18,19], as well as biomechanical factors [20]. The infl uence of mechanical force on bone growth is often considered through Hueter-Volkmann's law, which indicates that an increase in pressure in the epiphyseal growth zones has an inhibitory effect, as opposed to distension, which promotes longitudinal bone growth [21].…”

Maternal Subclinical and Clinical Hypothyroidism Effects on Rat Offspring: A Story of the Skin and its Derivatives

“…Maternal hypothyroidism down regulates thyroid hormone receptors in the offspring's skin [12], thus disabling triiodothyronine (T3) effects, as one of the main regulators of epidermal growth and differentiation [13]. Numerous studies have shown that the altered function of the maternal thyroid gland during pregnancy and lactation can affect the development of various fetal organs [14,15]. However, scarce research has been conducted on the effect of maternal thyroid hormones on the development of skin and its derivatives during prenatal and early postnatal development.…”

“…In particular, there is a lack of data about the infl uence of subclinical hypothyroidism of mothers during pregnancy on the development of the skin and its derivatives in the litter. It has been documented that subclinical and clinical hypothyroidism in mothers during pregnancy and lactation leads to offspring subclinical and clinical hypothyroidism [15][16][17]. Clinical hypothyroidism in mothers is characterized by rough coat, prolonged pregnancy and small litter size [15,18,19].…”

“…It has been documented that subclinical and clinical hypothyroidism in mothers during pregnancy and lactation leads to offspring subclinical and clinical hypothyroidism [15][16][17]. Clinical hypothyroidism in mothers is characterized by rough coat, prolonged pregnancy and small litter size [15,18,19]. In the pups, the overt form of hypothyroidism results in reduced body mass, lower thyroid hormone levels and higher thyroid index of activation [15].…”

“…Clinical hypothyroidism in mothers is characterized by rough coat, prolonged pregnancy and small litter size [15,18,19]. In the pups, the overt form of hypothyroidism results in reduced body mass, lower thyroid hormone levels and higher thyroid index of activation [15].…”