12 AASs such as ND affect the structure and function of the reproductive system via impacting the secretion of FSH and LH through a negative feedback mechanism.5,13 The hormonal assay of the present study showed a rise in the level of androgens and a drop in the levels of FSH, LH, estrogen, and progesterone in the blood circulation as well as the total and cortical volumes Inhibitors,research,lifescience,medical of the ovary and the number of the ovarian primordial follicles of the ND-treated rats. This result is in agreement with those obtained by Attardi et al.14Gao et al.15 and Karbalay-Doust et al.13These authors showed that androgen reduces gonadotropin release via

a negative feedback mechanism and decreases estrogen secretion in rats and mice. Synthetic steroids such as Estradiol Valerate suppress the serum levels of LH, FSH, and sex hormones and lead to a decrease in the number of the primordial follicles in rats.16,17ND may break up the function of the neuroendocrine axis, thus modifying the ovarian function and reducing the Inhibitors,research,lifescience,medical release of gonadotropins.18 Such a decline in the levels of estrogen and progesterone in the blood may induce structural changes such as a decrease in the number of the preantral and antral Inhibitors,research,lifescience,medical follicles in female rats and mice. Therefore, a reduction in the number of primordial follicles may be attributed to a reduction in the female

sex hormones. A decrease in the number of the primordial follicles in the ovary may give rise to a reduction in the volume of the ovarian cortex and, subsequently, the total ovarian volume. The destruction of various follicles following treatment with ND in rats has been demonstrated by Gerez et al.19 Elsewhere, Shirwalkar et al.16 reported that the exposure of adult rats to Estradiol Valerate results in the destruction of folliculogenesis and increase Inhibitors,research,lifescience,medical in apoptosis in the granulosa cells of secondary and antral follicles. This may suggest that the decrease in the volume of the ovary and cortex after ND administration is due to the reduction in the number of ovarian follicles. Inhibitors,research,lifescience,medical Yoshiko et al.20 reported that Ethinyl Estradiol influences the granulosa cells and oocytes

in mice and thus brings about the degeneration of primordial follicles. It seems that the interaction between degenerative follicular cells and oocytes triggers the degeneration Ribonucleotide reductase of primordial follicles. The present study revealed that the administration of hMG with a low dose of ND (3 mg/kg) led to an increase in the total volume of the ovary, its cortical region, and the number of the primordial follicles compared with a high dose of ND (10 mg/kg) in rats. Our literature review showed that gonadotropins can be considered a primary factor for the survival and maintenance of ovarian follicles. Wang et al.7 demonstrated that hMG increases the survival of ovarian follicles by the induction of the expression of vascular endothelial check details growth factor (VEGF) and improves blood supply reconstruction in the ovarian tissue in mice.