Epitalon: Protecting Aging Oocytes and Improving Fertility

General Description

Epitalon, a short peptide derived from epithalamin, has shown promising results in preventing age-related damage to oocytes. It exhibits antioxidant effects and stimulates the expression of antioxidant enzymes. In studies on aged oocytes, Epitalon was found to reduce the accumulation of reactive oxygen species (ROS) and decrease the fragmentation rate. It also alleviates DNA damage and reduces apoptosis in aging oocytes. These findings suggest that Epitalon has the potential to protect oocyte integrity and improve fertility. Further research is needed to explore its efficacy and potential therapeutic applications.

Figure 1. Injection of epitalon

Research progress in preventing age-related damage

In recent years, researchers have been exploring various agents to delay age-related damage to oocytes caused by prolonged culture in vitro. One such agent is Epitalon, a short peptide composed of the amino acids Ala-Glu-Asp-Gly. This peptide was originally derived from the analysis of epithalamin, a concentrate of the pineal gland. Studies on male rats have shown that Epitalon exhibits direct antioxidant effects and stimulates the expression of antioxidant enzymes such as superoxide dismutase (SOD) and ceruloplasmin. Additionally, in vivo studies have demonstrated that Epitalon has regenerative and life-prolonging effects, as well as positive effects on hormonal levels, immune responses, and the thyroid gland. In vitro, Epitalon helps prevent premature cell aging and inhibits tumor development in somatic cells. However, it is still unclear whether Epitalon can prevent post-ovulatory oocyte aging in vitro. Current research primarily focuses on exploring effective measures to delay oocyte aging through antioxidants, regulation of maturation-promoting factor (MPF) activity, regulation of oocyte metabolism, and regulation of apoptosis signaling pathways. Further studies are needed to determine the potential benefits of Epitalon in preventing age-related damage to oocytes during in vitro culture. ¹

Epitalon reduces the level of reactive oxygen species in aged oocyte

The researchers investigated the effect of Epitalon on reactive oxygen species (ROS) levels and oocyte aging. They found that the accumulation of intracellular ROS is a manifestation of post-ovulatory oocyte aging. To test the efficiency of Epitalon in scavenging ROS, different concentrations of Epitalon were added to the culture medium of aged oocytes. The results showed that 0.1mM Epitalon significantly reduced the level of ROS compared to the aged group, while higher concentrations of Epitalon did not have the same effect. This suggests that 0.1mM concentration of Epitalon can effectively reduce ROS in aging oocytes. Furthermore, the researchers examined the impact of Epitalon on oocyte fragmentation during aging and parthenogenetic activation. They observed that oocytes in the control group maintained normal morphology, while the aged group showed a higher incidence of fragmentation. However, supplementation with 0.1mM Epitalon significantly reduced the fragmentation rate in aged oocytes. Additionally, Epitalon also decreased the rate of cytoplasmic fragmentation during parthenogenetic activation of aged oocytes. Overall, these findings suggest that Epitalon has the potential to reduce ROS levels and protect the integrity of aging oocytes. This research provides valuable insights into the use of Epitalon as a potential therapeutic agent for improving oocyte quality and fertility. ²

Epitalon alleviates DNA damage and apoptosis of aging oocytes

Epitalon is a substance that has been found to alleviate DNA damage and apoptosis in aging oocytes. As oocytes age, oxidative stress and DNA damage increase, leading to accelerated apoptosis. In this study, we aimed to assess the extent of DNA damage in both the aged oocyte group and the group treated with Epitalon. The results showed that the fluorescence intensity of γH2AX signals, which indicate DNA damage, was significantly higher in aged oocytes compared to fresh controls. However, the addition of Epitalon during the aging culture was able to reduce DNA damage. Additionally, mitochondria play a role in regulating cell apoptosis. When cells age or become damaged, the mitochondrial membrane potential decreases, leading to the expression of apoptotic factors. We hypothesized that age-induced mitochondrial abnormalities would accelerate apoptosis in oocytes. Using Annexin-V binding to phosphatidylserine, we detected early cell apoptosis. The fluorescence signal indicating apoptosis was more pronounced in aging oocytes, but it was reduced in the Epitalon-treated group. This suggests that the addition of an appropriate concentration of Epitalon in vitro can decrease the degree of early apoptosis in oocytes. Overall, these findings demonstrate the potential of Epitalon to alleviate DNA damage and apoptosis in aging oocytes. ²

Reference

1. Khavinson VK, Izmaylov DM, Obukhova LK, Malinin VV. Effect of epitalon on the lifespan increase in Drosophila melanogaster. Mech Ageing Dev. 2000;120(1-3):141-149.

2. Yue X, Liu SL, Guo JN, et al. Epitalon protects against post-ovulatory aging-related damage of mouse oocytes in vitro. Aging (Albany NY). 2022;14(7):3191-3202.

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