Effect of androgen treatment on ovarian follicular development in diminished ovarian reserve in vivo rat model

The aim of this study was to determine the efficacy and molecular mechanism of dehydroepiandrosterone (DHEA) that added to the controlled ovarian hyperstimulation (COH) protocol in cases of diminished ovarian reserve (DOR), which is one of the causes of infertility. In order to determine the efficacy of DHEA both alone and combination with the COH protocol in the low and normal ovarian reserve experimental groups, 75 Spraque Dawley female rats were divided into 15 groups. In our study, the experimental animal model of DOR was composed by 4-Vinylcyclohexene diepoxide (VCD) injections at a dose of 160 mg/kg/day for 15 days. Subjects with normal ovarian reserve were injected with Dimethyl Sulfoxide (DMSO) for the same period. After VCD or DMSO injections, DHEA injections were administered at a dose of 60 mg/kg/day for 45 days. COH protocol was then applied to the subjects. In ovarian tissues obtained from sacrificed subjects, Cyclooxygenase-2 (COX-2) gene expression levels were analyzed by Polymerase Chain Reaction technique, morphological evaluation and ovarian follicle count were performed by hematoxylin-eosin staining. It was determined that VCD injections caused a decrease in the number of follicles at different stages of development and an increase in the number of atretic follicles and COX-2 gene expression levels in the ovarian tissues. While DHEA injections did not affect folliculogenesis and COX-2 gene expression levels in subjects with normal ovarian reserve, it was determined that DHEA injections caused a decrease in atretic follicle counts and an increase in COX-2 gene expression levels in subjects with low ovarian reserve. DHEA injections before the COH protocol affected folliculogenesis positively in both low and normal ovarian reserve experimental groups, and thus enhanced the efficiency of the COH protocol. Also, DHEA decreased COX-2 gene expression levels in all subjects. This study contributed to the literature on the effectiveness and molecular mechanism of the DHEA on the ovarian microenvironment and the appendability of DHEA in the COH protocol.