Zahra Shaaban - Department of Animal Science, College of Agriculture, Shiraz University, Shiraz, Iran
Amin Tamadon - The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
Mohammad Reza Jafarzadeh Shirazi - Department of Animal Science, College of Agriculture, Shiraz University, Shiraz, Iran
Mohammad Javad Zamiri - Department of Animal Science, College of Agriculture, Shiraz University, Shiraz, Iran
Amin Derakhshanfar - Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

Objective(s): Despite prevalence of polycystic ovary syndrome (PCOS) among childbearing women and development of many animal models for this syndrome, information on its etiology is still scarce. The intrauterine hyperandrogenic environment may underlie changes at the level of hypothalamus, pituitary, ovary organization in female offspring, and PCOS later in life. Letrozole has been shown to mimic reproductive and metabolic characteristics of PCOS in adult rodent models. Therefore, this research aimed to assess the condition in a prenatal letrozole-treated rat model. Materials and Methods: Twenty-eight female rats dams receiving letrozole at certain doses during late pregnancy were used in the trial.  Pregnant Sprague-Dawley rats (n=۲۱) received letrozole treatment on gestation days ۱۶–۱۸ at doses of ۱.۲۵, ۱.۰, ۰.۷۵, ۰.۵, and ۰.۲۵ mg/kg body weight (BW).    Results: Prenatal letrozole treatment delayed parturition time and reduced the litter size in pregnant dams (P<۰.۰۰۰۱). Late puberty onset, irregular ovarian cyclicity, increased anogenital distance (AGD), body weight gain, serum testosterone concentration, and reduced estradiol levels (P<۰.۰۰۰۱) were observed in the female offspring of dams receiving ۱.۲۵ and ۱ mg/kg BW letrozole. Furthermore, letrozole at ۱.۲۵ and ۱ mg/kg BW showed increased RFRP and decreased GnRH mRNA expression (P<۰.۰۰۰۱). Letrozole treatment at doses of ۱ mg/kg BW and lower was not fetotoxic. Conclusion: It was concluded that ۱ mg/kg BW letrozole may be suggested for prenatal PCOS induction. 

Gonadotropin-Releasing Hormone, Hypothalamus, Letrozole, Polycystic ovary syndrome Prenatal, Rat, RFamide-related peptide-۳