TY  - JOUR
AU  - Milošević, Ivan
AU  - Radovanovic, Anita
AU  - Danilović Luković, Jelena
AU  - Luzajic Bozinovski, Tijana
AU  - Sourice-Petit, Sophie
AU  - Beck-Cormier, Sarah
AU  - Guicheux, Jerome
AU  - Kovačević Filipović, Milica
PY  - 2018
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2471
AB  - 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, influences the process of offspring endochondral ossification 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 calcified 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.
PB  - Faculty of Veterinary Medicine, University of Belgrade, Serbia
T2  - Acta Veterinaria-Beograd
T1  - Effect of subclinical and overt form of rat maternal hypothyroidism on offspring endochondral bone formation
EP  - 320
IS  - 3
SP  - 301
VL  - 68
DO  - 10.2478/acve-2018-0026
ER  - 

@article{
author = "Milošević, Ivan and Radovanovic, Anita and Danilović Luković, Jelena and Luzajic Bozinovski, Tijana and Sourice-Petit, Sophie and Beck-Cormier, Sarah and Guicheux, Jerome and Kovačević Filipović, Milica",
year = "2018",
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, influences the process of offspring endochondral ossification 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 calcified 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.",
publisher = "Faculty of Veterinary Medicine, University of Belgrade, Serbia",
journal = "Acta Veterinaria-Beograd",
title = "Effect of subclinical and overt form of rat maternal hypothyroidism on offspring endochondral bone formation",
pages = "320-301",
number = "3",
volume = "68",
doi = "10.2478/acve-2018-0026"
}

Milošević, I., Radovanovic, A., Danilović Luković, J., Luzajic Bozinovski, T., Sourice-Petit, S., Beck-Cormier, S., Guicheux, J.,& Kovačević Filipović, M.. (2018). Effect of subclinical and overt form of rat maternal hypothyroidism on offspring endochondral bone formation. in Acta Veterinaria-Beograd
Faculty of Veterinary Medicine, University of Belgrade, Serbia., 68(3), 301-320.
https://doi.org/10.2478/acve-2018-0026

Milošević I, Radovanovic A, Danilović Luković J, Luzajic Bozinovski T, Sourice-Petit S, Beck-Cormier S, Guicheux J, Kovačević Filipović M. Effect of subclinical and overt form of rat maternal hypothyroidism on offspring endochondral bone formation. in Acta Veterinaria-Beograd. 2018;68(3):301-320.
doi:10.2478/acve-2018-0026 .

Milošević, Ivan, Radovanovic, Anita, Danilović Luković, Jelena, Luzajic Bozinovski, Tijana, Sourice-Petit, Sophie, Beck-Cormier, Sarah, Guicheux, Jerome, Kovačević Filipović, Milica, "Effect of subclinical and overt form of rat maternal hypothyroidism on offspring endochondral bone formation" in Acta Veterinaria-Beograd, 68, no. 3 (2018):301-320,
https://doi.org/10.2478/acve-2018-0026 . .

TY  - CONF
AU  - Milošević, Ivan
AU  - Danilović Luković, Jelena
AU  - Lužajić, Tijana
AU  - Milošević, Sandra
AU  - Radovanovic, Anita
AU  - Sourice-Petit, Sophie
AU  - Guicheux, Jerome
AU  - Kovačević Filipović, Milica
PY  - 2017
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2695
AB  - The effects of maternal hypothyroidism on the 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 prenatal and early postnatal
development. Our previous studies have demonstrated that hypothyroid rat pups had reduced
growth plate thickness.
The aim of the study was to assess bone turnover by defining the expression of tartrateresistant
acid phosphatase (TRAP), alkaline phosphatase tissue nonspecific isozyme (ALPL)
and mRNA for dentin matrix acidic phosphoprotein (DMP1) in the 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. The control group was untreated. Five, sevenday-
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 ALPL and in situ hybridization for
DMP1. The area of the TRAP positive signal, optical density of ALPL immunostaining, and the
number of DMP1 positive cells were evaluated using the Image J. Expression of TRAP and ALPL
in the proximal tibial growth plate were lower in the hypothyroid pups, and the number of cells
expressing mRNA for DMP1 was decreased.
TRAP is a marker of osteoclast activity. Osteoclasts are multinucleated cells which are
necessary for bone and mineralized cartilage resorption. In osteoblasts ALPL and DMP1 are
expressed and they have an important role in the process of endochondral ossification. As we
have shown that TRAP, ALPL and DMP1 are decreased, we may conclude that maternal SHT in
rats leads to compromised cartilage to bone transition, and delayed osteogenic differentiation
in the early infantile period.
PB  - Faculty of Veterinary Medicine, University of Zagreb, Croatia
C3  - 7th International Congress, Veterinary Science and Profession, Zagreb, October 5th-7th 2017
T1  - Subclinical hypothyroidism in gravide albino oxford rats cause delayed osteogenic differentiation in newborns
EP  - 151
SP  - 151
UR  - https://hdl.handle.net/21.15107/rcub_rimsi_2695
ER  - 

@conference{
author = "Milošević, Ivan and Danilović Luković, Jelena and Lužajić, Tijana and Milošević, Sandra and Radovanovic, Anita and Sourice-Petit, Sophie and Guicheux, Jerome and Kovačević Filipović, Milica",
year = "2017",
abstract = "The effects of maternal hypothyroidism on the 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 prenatal and early postnatal
development. Our previous studies have demonstrated that hypothyroid rat pups had reduced
growth plate thickness.
The aim of the study was to assess bone turnover by defining the expression of tartrateresistant
acid phosphatase (TRAP), alkaline phosphatase tissue nonspecific isozyme (ALPL)
and mRNA for dentin matrix acidic phosphoprotein (DMP1) in the 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. The control group was untreated. Five, sevenday-
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 ALPL and in situ hybridization for
DMP1. The area of the TRAP positive signal, optical density of ALPL immunostaining, and the
number of DMP1 positive cells were evaluated using the Image J. Expression of TRAP and ALPL
in the proximal tibial growth plate were lower in the hypothyroid pups, and the number of cells
expressing mRNA for DMP1 was decreased.
TRAP is a marker of osteoclast activity. Osteoclasts are multinucleated cells which are
necessary for bone and mineralized cartilage resorption. In osteoblasts ALPL and DMP1 are
expressed and they have an important role in the process of endochondral ossification. As we
have shown that TRAP, ALPL and DMP1 are decreased, we may conclude that maternal SHT in
rats leads to compromised cartilage to bone transition, and delayed osteogenic differentiation
in the early infantile period.",
publisher = "Faculty of Veterinary Medicine, University of Zagreb, Croatia",
journal = "7th International Congress, Veterinary Science and Profession, Zagreb, October 5th-7th 2017",
title = "Subclinical hypothyroidism in gravide albino oxford rats cause delayed osteogenic differentiation in newborns",
pages = "151-151",
url = "https://hdl.handle.net/21.15107/rcub_rimsi_2695"
}

Milošević, I., Danilović Luković, J., Lužajić, T., Milošević, S., Radovanovic, A., Sourice-Petit, S., Guicheux, J.,& Kovačević Filipović, M.. (2017). Subclinical hypothyroidism in gravide albino oxford rats cause delayed osteogenic differentiation in newborns. in 7th International Congress, Veterinary Science and Profession, Zagreb, October 5th-7th 2017
Faculty of Veterinary Medicine, University of Zagreb, Croatia., 151-151.
https://hdl.handle.net/21.15107/rcub_rimsi_2695

Milošević I, Danilović Luković J, Lužajić T, Milošević S, Radovanovic A, Sourice-Petit S, Guicheux J, Kovačević Filipović M. Subclinical hypothyroidism in gravide albino oxford rats cause delayed osteogenic differentiation in newborns. in 7th International Congress, Veterinary Science and Profession, Zagreb, October 5th-7th 2017. 2017;:151-151.
https://hdl.handle.net/21.15107/rcub_rimsi_2695 .

Milošević, Ivan, Danilović Luković, Jelena, Lužajić, Tijana, Milošević, Sandra, Radovanovic, Anita, Sourice-Petit, Sophie, Guicheux, Jerome, Kovačević Filipović, Milica, "Subclinical hypothyroidism in gravide albino oxford rats cause delayed osteogenic differentiation in newborns" in 7th International Congress, Veterinary Science and Profession, Zagreb, October 5th-7th 2017 (2017):151-151,
https://hdl.handle.net/21.15107/rcub_rimsi_2695 .