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

Luzajic Bozinovski, Tijana; Danilović Luković, Jelena; Nikolić, Anja; Radovanović, Anita; Marković, Danica; Kovačević Filipović, Milica; Vasić, Mirjana; Milošević, Ivan

(Walter de Gruyter {GmbH}, 2023)

TY  - JOUR
AU  - Luzajic Bozinovski, Tijana
AU  - Danilović Luković, Jelena
AU  - Nikolić, Anja
AU  - Radovanović, Anita
AU  - Marković, Danica
AU  - Kovačević Filipović, Milica
AU  - Vasić, Mirjana
AU  - Milošević, Ivan
PY  - 2023
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2453
AB  - Epidermis stem cells have a crucial role through the processes of proliferation and
differentiation, to replace cells that are constantly lost during tissue turnover or
following injury. On the other hand, thyroid hormones regulate the proliferation and
differentiation of epidermal cells and thus significantly influence the homeostasis
of the skin. It is well known that maternal hypothyroidism during pregnancy leads
to impaired development of many organ systems in their offspring. However, there
is a lack of data about the influence of maternal subclinical hypothyroidism during
pregnancy and lactation on the development of the skin and its derivatives in the litter.
The aim of this study was to investigate the effects of maternal thyroid dysfunction on
the development of the skin and its derivatives in their offspring in the early postnatal
period. Antithyroid substance 6-n-propyl-2-thiouracil was added into the drinking water
to female Albino Oxfords rats from the beginning of pregnancy and during lactation,
with the aim to induce subclinical and overt form of hypothyroidism. Skin samples
were taken from male pups within twenty-four hours and seven days after birth. The
main findings of this investigation were that both forms of maternal hypothyroidism
lead to serious damage of the epidermis in pups in terms of pronounced hyperkeratosis
and reduction of the germinal layer along with a reduced number of hair follicles and
their delayed morphogenesis. Epidermal impairments were more pronounced in pups
with the overt form of hypothyroidism while offspring with the subclinical form had
impairments that were less pronounced and delayed in occurrence.
PB  - Walter de Gruyter {GmbH}
T2  - Acta Veterinaria-Beograd
T1  - Maternal Subclinical and Clinical Hypothyroidism Effects on Rat Offspring: A Story of the Skin and its Derivatives
EP  - 248
IS  - 2
SP  - 231
VL  - 73
DO  - 10.2478/acve-2023-0018
ER  - 
@article{
author = "Luzajic Bozinovski, Tijana and Danilović Luković, Jelena and Nikolić, Anja and Radovanović, Anita and Marković, Danica and Kovačević Filipović, Milica and Vasić, Mirjana and Milošević, Ivan",
year = "2023",
abstract = "Epidermis stem cells have a crucial role through the processes of proliferation and
differentiation, to replace cells that are constantly lost during tissue turnover or
following injury. On the other hand, thyroid hormones regulate the proliferation and
differentiation of epidermal cells and thus significantly influence the homeostasis
of the skin. It is well known that maternal hypothyroidism during pregnancy leads
to impaired development of many organ systems in their offspring. However, there
is a lack of data about the influence of maternal subclinical hypothyroidism during
pregnancy and lactation on the development of the skin and its derivatives in the litter.
The aim of this study was to investigate the effects of maternal thyroid dysfunction on
the development of the skin and its derivatives in their offspring in the early postnatal
period. Antithyroid substance 6-n-propyl-2-thiouracil was added into the drinking water
to female Albino Oxfords rats from the beginning of pregnancy and during lactation,
with the aim to induce subclinical and overt form of hypothyroidism. Skin samples
were taken from male pups within twenty-four hours and seven days after birth. The
main findings of this investigation were that both forms of maternal hypothyroidism
lead to serious damage of the epidermis in pups in terms of pronounced hyperkeratosis
and reduction of the germinal layer along with a reduced number of hair follicles and
their delayed morphogenesis. Epidermal impairments were more pronounced in pups
with the overt form of hypothyroidism while offspring with the subclinical form had
impairments that were less pronounced and delayed in occurrence.",
publisher = "Walter de Gruyter {GmbH}",
journal = "Acta Veterinaria-Beograd",
title = "Maternal Subclinical and Clinical Hypothyroidism Effects on Rat Offspring: A Story of the Skin and its Derivatives",
pages = "248-231",
number = "2",
volume = "73",
doi = "10.2478/acve-2023-0018"
}
Luzajic Bozinovski, T., Danilović Luković, J., Nikolić, A., Radovanović, A., Marković, D., Kovačević Filipović, M., Vasić, M.,& Milošević, I.. (2023). Maternal Subclinical and Clinical Hypothyroidism Effects on Rat Offspring: A Story of the Skin and its Derivatives. in Acta Veterinaria-Beograd
Walter de Gruyter {GmbH}., 73(2), 231-248.
https://doi.org/10.2478/acve-2023-0018
Luzajic Bozinovski T, Danilović Luković J, Nikolić A, Radovanović A, Marković D, Kovačević Filipović M, Vasić M, Milošević I. Maternal Subclinical and Clinical Hypothyroidism Effects on Rat Offspring: A Story of the Skin and its Derivatives. in Acta Veterinaria-Beograd. 2023;73(2):231-248.
doi:10.2478/acve-2023-0018 .
Luzajic Bozinovski, Tijana, Danilović Luković, Jelena, Nikolić, Anja, Radovanović, Anita, Marković, Danica, Kovačević Filipović, Milica, Vasić, Mirjana, Milošević, Ivan, "Maternal Subclinical and Clinical Hypothyroidism Effects on Rat Offspring: A Story of the Skin and its Derivatives" in Acta Veterinaria-Beograd, 73, no. 2 (2023):231-248,
https://doi.org/10.2478/acve-2023-0018 . .

Hypothyroidism in pregnant rats affects proliferation and cell death of growth plate chondrocytes in pups

Milošević, Ivan; Luzajic Bozinovski, Tijana; Danilović Luković, Jelena; Gajdov, Vladimir; Marković, Danica; Kovačević Filipović, Milica; Radovanovic, Anita

(Faculty of Veterinary Medicine, University of Zagreb, Croatia, 2021)

TY  - CONF
AU  - Milošević, Ivan
AU  - Luzajic Bozinovski, Tijana
AU  - Danilović Luković, Jelena
AU  - Gajdov, Vladimir
AU  - Marković, Danica
AU  - Kovačević Filipović, Milica
AU  - Radovanovic, Anita
PY  - 2021
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2609
AB  - Overt and subclinical maternal hypothyroidism affects cartilage and bone extracellular matrix formation during fetal endochondral bone development. Less is known about the effect maternal hypothyroidism has on cell proliferation and death of growth plate chondrocytes.
This study aimed to evaluate the expression of proliferation (Ki67), autophagy (LC3) and apoptosis (caspase 3) markers in the epiphyseal cartilage of the tibia in pups from subclinical and overt hypothyroid does, in their early postnatal development.
Hypothyroidism was induced with propylthiouracil using low (1.5 mg/L) for subclinical (H1) and high dose (150 mg/L) for overt (H2) form. Propylthiouracil was administered through drinking water in pregnant Albino Oxford does from the first day of gravidity and during lactation. Control (C) group was not treated. Six, seven-day-old male pups from each group were euthanized. Histological examinations were performed on paraffin sections of the proximal tibial growth plate. Immunohistochemistry was used to assess the expression of Ki67, LC3 and caspase 3. The number of Ki67 positive chondrocytes was evaluated in the resting and proliferating zone using Image J. The expression of LC3 was performed by counting the number of positive dots in chondrocytes.
The number of Ki67 positive chondrocytes was higher in both hypothyroid groups, while the number of LC3 positive dots per cell was lower indicating that the chondrocyte cell cycle in hypothyroid animals is faster and that the basal level of autophagy is reduced due to frequent mitosis. Compared to controls, caspase 3 expression in the terminal hypertrophic chondrocytes was reduced in H1 and completely absent in H2 pups which might indicate impaired differentiation. We conclude that both forms of maternal hypothyroidism in rats lead to accelerated proliferation, slowed autophagy and compromised apoptosis of terminal hypertrophic chondrocytes in the early infantile period and a delay in cartilage to bone transition.
PB  - Faculty of Veterinary Medicine, University of Zagreb, Croatia
C3  - 9th International Conference Veterinary Science and Profession 2021, Zagreb
T1  - Hypothyroidism in pregnant rats affects proliferation and cell death of growth plate chondrocytes in pups
EP  - 114
SP  - 114
UR  - https://hdl.handle.net/21.15107/rcub_rimsi_2609
ER  - 
@conference{
author = "Milošević, Ivan and Luzajic Bozinovski, Tijana and Danilović Luković, Jelena and Gajdov, Vladimir and Marković, Danica and Kovačević Filipović, Milica and Radovanovic, Anita",
year = "2021",
abstract = "Overt and subclinical maternal hypothyroidism affects cartilage and bone extracellular matrix formation during fetal endochondral bone development. Less is known about the effect maternal hypothyroidism has on cell proliferation and death of growth plate chondrocytes.
This study aimed to evaluate the expression of proliferation (Ki67), autophagy (LC3) and apoptosis (caspase 3) markers in the epiphyseal cartilage of the tibia in pups from subclinical and overt hypothyroid does, in their early postnatal development.
Hypothyroidism was induced with propylthiouracil using low (1.5 mg/L) for subclinical (H1) and high dose (150 mg/L) for overt (H2) form. Propylthiouracil was administered through drinking water in pregnant Albino Oxford does from the first day of gravidity and during lactation. Control (C) group was not treated. Six, seven-day-old male pups from each group were euthanized. Histological examinations were performed on paraffin sections of the proximal tibial growth plate. Immunohistochemistry was used to assess the expression of Ki67, LC3 and caspase 3. The number of Ki67 positive chondrocytes was evaluated in the resting and proliferating zone using Image J. The expression of LC3 was performed by counting the number of positive dots in chondrocytes.
The number of Ki67 positive chondrocytes was higher in both hypothyroid groups, while the number of LC3 positive dots per cell was lower indicating that the chondrocyte cell cycle in hypothyroid animals is faster and that the basal level of autophagy is reduced due to frequent mitosis. Compared to controls, caspase 3 expression in the terminal hypertrophic chondrocytes was reduced in H1 and completely absent in H2 pups which might indicate impaired differentiation. We conclude that both forms of maternal hypothyroidism in rats lead to accelerated proliferation, slowed autophagy and compromised apoptosis of terminal hypertrophic chondrocytes in the early infantile period and a delay in cartilage to bone transition.",
publisher = "Faculty of Veterinary Medicine, University of Zagreb, Croatia",
journal = "9th International Conference Veterinary Science and Profession 2021, Zagreb",
title = "Hypothyroidism in pregnant rats affects proliferation and cell death of growth plate chondrocytes in pups",
pages = "114-114",
url = "https://hdl.handle.net/21.15107/rcub_rimsi_2609"
}
Milošević, I., Luzajic Bozinovski, T., Danilović Luković, J., Gajdov, V., Marković, D., Kovačević Filipović, M.,& Radovanovic, A.. (2021). Hypothyroidism in pregnant rats affects proliferation and cell death of growth plate chondrocytes in pups. in 9th International Conference Veterinary Science and Profession 2021, Zagreb
Faculty of Veterinary Medicine, University of Zagreb, Croatia., 114-114.
https://hdl.handle.net/21.15107/rcub_rimsi_2609
Milošević I, Luzajic Bozinovski T, Danilović Luković J, Gajdov V, Marković D, Kovačević Filipović M, Radovanovic A. Hypothyroidism in pregnant rats affects proliferation and cell death of growth plate chondrocytes in pups. in 9th International Conference Veterinary Science and Profession 2021, Zagreb. 2021;:114-114.
https://hdl.handle.net/21.15107/rcub_rimsi_2609 .
Milošević, Ivan, Luzajic Bozinovski, Tijana, Danilović Luković, Jelena, Gajdov, Vladimir, Marković, Danica, Kovačević Filipović, Milica, Radovanovic, Anita, "Hypothyroidism in pregnant rats affects proliferation and cell death of growth plate chondrocytes in pups" in 9th International Conference Veterinary Science and Profession 2021, Zagreb (2021):114-114,
https://hdl.handle.net/21.15107/rcub_rimsi_2609 .