Low estrogen level in aged mice leads to abnormal oogenesis affecting the quality of surrounded nucleolus-type immature oocytes

Abstract

Context With aging, various problems in the reproductive system emerge, especially in females. However, our understanding of reproductive aging in livestock and humans is limited. Aims We aimed to investigate reproductive changes between young and aged mice. Methods Eight- to ten-week-old female mice were used as the young group, and 10-month-old mice were studied as the aged group. Reproductive changes were investigated from physiological, histological, cytological, and epigenetic perspectives. Key results The estrus cycle was shortened (P < 0.0001), and the estradiol (E2) concentration was lower in aged mice (P < 0.01), whereas the progesterone (P4) concentration did not differ between young and aged mice (P > 0.05). The histological results revealed a lower number of antral follicles in the ovary and disordered epithelial tissue structures in the oviducts in aged mice. During oogenesis, the surrounded nucleolus (SN)-type oocytes in aged mice exhibited increased mitochondrial agglutination (P < 0.05) and cellular apoptosis (P < 0.01) as well as decreased H3K36 triple-methylation (P < 0.001). Although many defects existed, the oocytes from aged mice could normally support cellular reprogramming after somatic cell nuclear transfer. Conclusions Our results indicate that the reduced levels of reproductive hormones in aged females lead to shorter estrus cycles and reduced follicular development, leading to abnormal oogenesis, particularly in SN-type immature oocytes. Implications These results provide new insight that enhance our understanding and improve the reproductive ability of aged females.