الفهرس 
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Abstract
Doramectin is a third-generation of avermectins family and one of the most effective veterinary antiparasitic drugs that produced by the fermentation of a mutant Streptomyces avermitilis. Doramectin is used against endoparasitic nematodes and ectoparasitic insects in animals. The present study was carried out to investigate the adverse effects of doramectin either in a single or double therapeutic dose on fertility and mating behavior of female Sprague Dawley rats, as well as, their effects on oxidative stress and antioxidant defense markers. Moreover, histopathological examination of ovary, uterus and anterior pituitary gland was applied. A total number of fifty seven rats including forty eight healthy cyclic female Sprague-Dawley rats (12 weeks old and 180-250gm body weight) and nine mature male Sprague-Dawley rats (12 weeks old and 200-300gm body weight) were used in this study. The female rats with estrus phase that detected by daily vaginal smear were divided into two experiments as follow : Experiment 2 (The effect of doramectin on mating behavior and pregnancy in female rats) : Eighteen clinically healthy mature female rats (180-250gm) were divided randomly into 3 equal groups (each of 6 rats) as the following : a- First group (control) : Female rats with regular estrous cycle were firstly injected subcutaneously with sesame oil as a single dose. Then female rats were paired overnight with sexually active males in the ratio of 2:1 in wire floor mating cages. b- Second group : Female rats with regular estrous cycle were firstly injected subcutaneously with a single therapeutic dose of doramectin (200µg/kg B.wt) before being placed with males (with proven fertility) in the ratio of 2:1 overnight in wire floor mating cages. c- Third group : Female rats with regular estrous cycle were firstly injected subcutaneously with double therapeutic dose of doramectin (400µg/kg B.wt) before being placed with sexually active males in the ratio of 2:1 overnight in wire floor mating cages. The presence of sperm cells in the vaginal smear indicates successful mating and pregnancy. The day on which the sperm cells were found in the vaginal smear was considered as day 1 of pregnancy. The female rats were separated from the males once mating had been confirmed. Then female fertility index was determined according to (Wato et al., 2009). The female rats were kept under daily observation until the 15th day of gestation (the fetus is big enough to be visually counted). Afterwards, they were laparotomized under high ether anesthesia and their uterine horns were removed. Then number of implantation and resorption sites in both control and doramectin administrated groups were counted according to the method described by (Hyacinth and Nwocha, 2011). summary of main findings are: a) The effect of doramectin on the levels of serum gonadotropic hormones (FSH and LH): Doramectin at single and double therapeutic doses induced a significant decrease in the levels of serum LH and FSH along the whole experimental period.b) – The effect of doramectin on the serum estradiol level : Subcutaneous injection of single and double therapeutic doses of doramectin evoked a significant decrease in the levels of serum estradiol along the whole experimental period. c) – The effect of doramectin on the serum progesterone level: Rats treated with single and double therapeutic doses of doramectin showed a significant increase in serum progesterone levels at all sampling times. e) Histopathological findings:1- Ovarian lesions: On the 30th day post treatment, ovaries of single therapeutic dose displayed partial destruction of germinal epithelium with numerous atretic follicles and mild proliferation of stromal cells. However, ovaries of doramectin double therapeutic dose treated group showed intense proliferation of stromal cells together with degeneration and cyst formation of some developing follicles, hemorrhage and hyperemia in the majority of stromal blood vessels, intense destruction of surface epithelium and atretic follicles were present. 2- Uterine lesions : At the end of the experiment (the 30th day post treatment), doramectin revealed mild proliferation of endometrial epithelium, acute cell swelling with vesicle formation, some endometrial glands appeared cystic with proliferative stromal cells mainly eosinophils and hyperplastic myometrial smooth muscles was infiltrated with eosinophils in single and double therapeutic doses. 3- Anterior pituitary gland lesions : On the 30th day post treatment, anterior pituitary glands evoked hypertrophied and vacuolated endocrine cells (acute cells swelling) with a few pyknotic cells in pars distales of adenohyposis in both tested dose.