الفهرس 
OVARIAN STRUCTUREOnly 14 pages are availabe for public view
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Abstract
Thyroid hormones are the key regulators for a variety of biological processes, including growth, metabolism, development and differentiation in different tissues and organs including the ovary.
The present study aimed at investigating the hypothesis that hypothyroidism in females impairs fertility by direct and indirect effects on ovaries. To confirm the current hypothesis, the anti-thyroid drug Carbimazole was used to induce a state of hypothyroidism and examined the outcome of its application.
For this purpose, 45 adult female albino rats each weighing 180-220 grams, were used and were classified into three equal groups: group I (Euthyroid, Control group): was composed of 15 rats, they received 0.5 ml of distilled water every day orally by gastric tube for three months, group II (Hypothyroid group): was composed of 15 rats, each of which received Carbimazole at a dose of 5mg dissolved in distilled water every day orally by gastric tube for three months to induce hypothyroidism and group III (Recovery Group): was composed of 15 rats and they ceased to receive Carbimazole for three months to examine the changes after the stoppage of the treatment.
The changes that occurred after the use of Carbimazole, were tested by laboratory studies: measuring the serum levels of thyroid stimulating hormone, total thyroxine, total tri-iodothyronine, follicular stimulating hormone, Luteinizing hormone, estradiol and prolactin.
Moreover, the effects on the structure of the ovary were investigated via histological and immuno-histochemical studies at the end of the experiment, using light microscopy and analyzed by image and statistical analyses.
After sacrifice of the rats, their ovaries were separated and processed for histological examination using Hematoxylin and Eosin, Periodic Acid Schiff and Masson’s Trichrome. In addition, semithin preparations were made and stained by Toluidine Blue. Furthermore, the ovarian sections were processed for immuno-histochemial staining using Vimentin, thyroid receptor alpha 1 and α- smooth muscle actin stains.
The studied histological and semithin preparations revealed a change in the normal architecture of the ovary, where the ovarian cortex showed an apparent decrease in the number of growing follicles with large fluid-filled cystic follicles and multiple atretic follicles. Marked condensation of the interstitial cells among the follicular component of the cortex was identified with engorged blood vessels which was reversed upon stoppage of the intake of the drug.
The immunohistochemical results using vimentin revealed that the expression of vimentin agreed with the previous works of other investigators. It was attributed to increase in cystic follicle formation and atresia of follicles with engorgement of blood vessels due to drug intake which was reversed and returned almost to control appearance upon cessation of the intake. In addition, the expression of vimentin in the granulosa cells of the corpus luteum was an important detector of the viability of its cells and their proper functioning. Furthermore, the expression of vimentin in the walls of blood vessels denoted hyperactivity of the ovary in response to hypothyroidism. To the best of our knowledge these findings were not recorded in the current literatures.
The presence of thyroid receptor alpha 1 revealed the direct effect of thyroid hormones on the surface epithelium and stroma of the ovary making it sensitive to changes in the thyroid hormonal levels which may have a role in folliculogenesis and ovulation. In addition, the presence of thyroid hormone receptors in the follicles was necessary for inhibiting the apoptosis of the follicles and thus aid in maturity. For this reason, the decrease in expression of thyroid hormone receptors in cases of hypothyroidism was related to the decrease in number of follicles and increase in the rate of apoptosis.
It was observed that the negative staining with thyroid receptor alpha 1 of theca interna, theca externa, interstitial cells, the stroma surrounding the follicles as well as the primary follicle. The negative staining of the previously mentioned areas could be explained that these tissues do not need thyroid hormones for their proper functioning and may be influenced by other factors. The previous remarks were not discussed in current literatures to the best of our knowledge.
Moreover, the alpha smooth muscle immunostain showed strong staining of basal lamina with moderate staining of corona radiata and positive staining of the theca externa which explains the effect of alpha smooth actin on the contractile properties of the follicle that are necessary for increase in size and its presumed role in ovulation. In addition, intense positive staining around blood vessels was noticed and could be attributed to the hyper-function of the ovary in response to the stress caused by disturbed hormonal levels. Furthermore, the corpora lutea were properly functioning along with intense positive staining of the blood vessels within the corpus which can be related to the proper functioning as an endocrine gland despite the altered thyroid hormone levels. These findings are considered new and were not covered by current available literatures.
In conclusion, the use of Carbimazole in induction of hypothyroidism affected the ovary by acting on different levels.