title: Dietary-Induced Chronic Hypothyroidism Negatively Affects Rat Follicular Development and Ovulation Rate and Is Associated with Oxidative Stress.
abstract: The long-term effects of chronic hypothyroidism on ovarian follicular development in adulthood are not well known. Using a rat model of chronic diet-induced hypothyroidism initiated in the fetal period, we investigated the effects of prolonged reduced plasma thyroid hormone concentrations on the ovarian follicular reserve and ovulation rate in prepubertal (12-day-old) and adult (64-day-old and 120-day-old) rats. Besides, antioxidant gene expression, mitochondrial density and the occurrence of oxidative stress were analyzed. Our results show that continuous hypothyroidism results in lower preantral and antral follicle numbers in adulthood, accompanied by a higher percentage of atretic follicles, when compared to euthyroid age-matched controls. Not surprisingly, ovulation rate was lower in the hypothyroid rats. At the age of 120 days, the mRNA and protein content of superoxide dismutase 1 (SOD1) were significantly increased while catalase (CAT) mRNA and protein content was significantly decreased, suggesting a disturbed antioxidant defense capacity of ovarian cells in the hypothyroid animals. This was supported by a significant reduction in the expression of peroxiredoxin 3 ( ITALIC! Prdx3), thioredoxin reductase 1 ( ITALIC! Txnrd1), and uncoupling protein 2 ( ITALIC! Ucp2) and a downward trend in glutathione peroxidase 3 ( ITALIC! Gpx3) and glutathione S-transferase mu 2 ( ITALIC! Gstm2) expression. These changes in gene expression were likely responsible for the increased immunostaining of the oxidative stress marker 4-hydroxynonenal. Together these results suggest that chronic hypothyroidism initiated in the fetal/neonatal period results in a decreased ovulation rate associated with a disturbance of the antioxidant defense system in the ovary.
authors.affiliation: Human and Animal Physiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Li
authors.initials: L
authors.lastname: Meng
authors.affiliation: Human and Animal Physiology, Wageningen University, Wageningen, The Netherlands Institut für Experimentelle Endokrinologie, Charité Universitäts-Medizin Berlin, Berlin, Germany.
authors.forename: Eddy
authors.initials: E
authors.lastname: Rijntjes
authors.affiliation: Human and Animal Physiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Swarts
authors.affiliation: Human and Animal Physiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Annelies
authors.initials: A
authors.lastname: Bunschoten
authors.affiliation: Human and Animal Physiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Inge
authors.initials: I
authors.lastname: van der Stelt
authors.affiliation: Human and Animal Physiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Jaap
authors.initials: J
authors.lastname: Keijer
authors.affiliation: Human and Animal Physiology, Wageningen University, Wageningen, The Netherlands katja.teerds@wur.nl.
authors.forename: Katja
authors.initials: K
authors.lastname: Teerds
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001835:Body Weight; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D015870:Gene Expression; D007037:Hypothyroidism / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D007986:Luteinizing Hormone / Q000097:blood; D006080:Ovarian Follicle / Q000254:growth & development*; D010060:Ovulation; D018384:Oxidative Stress; D017208:Rats, Wistar; D012741:Sexual Maturation; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
chemical_list: D000975:Antioxidants; D014284:Triiodothyronine; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D013974:Thyroxine
keywords: follicular development; gene expression; hypothyroidism; ovary; oxidative damage