Flaxseed Lignans Alleviates Doxorubicin-Induced Premature Ovarian Insufficiency in Adult Female Mice

Premature ovarian insufficiency (POI) is a condition in which the ovarian function decreases beyond the extent of the normal range of young adults' age. This can be a consequence of cancer treatments like doxorubicin, leading to reproductive deterioration that hormonal replacement therapy cannot fully address. Flaxseed lignans are weak phytoestrogens that can mimic the effects of estrogen and alleviate POI-associated symptoms. Therefore, this study aimed to evaluate the potential of flaxseed lignans to improve the recovery from doxorubicin-induced POI in adult mice. Thirty-six regularly-cycling virgin female mice were randomly allocated into: normal, POI, and lignans-treated POI groups. These mice were assigned to either experiment I to assess cyclicity, ovarian hormones, ovarian histomorphometry, and immunohistochemistry; or to experiment II, where the females were mated to assess pregnancy rates, and embryos quantity and quality. Exposure to doxorubicin resulted in irregular estrous cycles, and significant decrease in body and ovarian weights, estradiol, follicular count, and pregnancy rate; while showed a significant increase in FSH and follicular atresia. Lignans treatment improved body and ovarian weights, and significantly ameliorated the decrease in estradiol levels, viable follicular count, as well as the pregnancy rate. Lignans have been also observed to reduce elevated FSH levels and the number of atretic follicles, while also helping to normalize estrous cycle regularity. In conclusion, flaxseed lignans, due to their estrogen-like effects, can help mitigate reproductive deteriorations caused by cancer treatments, which suggests their potential use in treating premature ovarian insufficiency.