Amelioration of ovarian injury in female mice by docosahexaenoic acid ethyl ester and its synthetic derivatives
Background. Commonly used chemotherapeutic drugs may cause damage to the ovaries. Although hormone-based treatments have been adopted clinically to decrease the ovarian injury risk, they do not achieve the desired therapeutic effects. Therefore, it is necessary to develop new treatments and programs for ovarian injury following chemotherapy. N-Benzyl docosahexaenamide (NB-DHA) was recently identified as a DHA derivative from maca. Based on the existing research on DHA and ovarian diseases, we speculate that NB-DHA might have positive effects on ovarian injury. Materials and methods. A cyclophosphamide (CTX) induced ovarian injury model was established in mice. DHA ethyl ester (DHA-EE) and NB-DHA were synthesized by transesterification and carbodiimide condensation, respectively. The purified substances were administered intragastrically. Estrous cycle, ovarian morphology, follicle number and morphology, sex hormone levels, mRNA levels of related genes, granular cell apoptosis ratios, and immune cell levels were analyzed using blood and tissue samples after DHA-EE and NB-DHA treatments. Results. Both NB-DHA and DHA-EE improved disorders of the estrous cycle, the ratio of normal and atretic follicles, hormone levels, regulated the expression of ovarian-related genes, reduced granulosa cell apoptosis, increased the expression of anti-Müllerian hormone and follicle-stimulating hormone receptor in ovarian tissues, and enhanced the ratio of CD4+ T cells to CD8+ T cells. The ameliorative effect of NB-DHA on ovarian injury was better than that of DHA-EE. Conclusions. Both DHA-EE and NB-DHA improved ovarian injury in mice via multiple epigenetic mechanisms. Moreover, synthetic NB-DHA is a promising agent for treating ovarian injury.