Many wonder about the impact of age on fertility. While it's commonly understood that age affects egg quality and increases chromosomal abnormalities, its influence on the endometrium is equally important. This article delves into how maternal age impacts endometrial receptivity and overall fertility, drawing from the latest research findings.
The Role of the Endometrium
The endometrium, the inner lining of the uterus, undergoes cyclic changes regulated by ovarian hormones, primarily estradiol (E2) and progesterone (P4). It has two layers: the functionalis, which sheds during menstruation and regenerates during the proliferative phase, and the basalis, which contains stem cells essential for maintaining endometrial integrity. Proper endometrial function is crucial for embryo implantation and pregnancy success.
Hormonal Changes with Age
As women age, the levels and responsiveness to E2 and P4 fluctuate, impacting endometrial proliferation and receptivity. Studies show variability in serum E2 concentrations among older women. Some research indicates elevated E2 levels in the follicular phase due to a disrupted feedback mechanism involving inhibin B and FSH. The expression of estrogen and progesterone receptors (ER and PR) in the endometrium also decreases with age, affecting endometrial thickness and morphology.
Cellular Aging and Senescence
Aging is linked with cellular senescence, where cells irreversibly stop dividing and secrete pro-inflammatory factors. Senescent cells accumulate with age, contributing to chronic inflammation, tissue fibrosis, and impaired endometrial function. The decidualization process, essential for embryo implantation, involves a controlled pro-inflammatory response. However, aging disrupts this balance, leading to inadequate decidualization and impaired receptivity.
Endometrial Inflammaging
Inflammaging refers to age-related chronic inflammation, which negatively affects endometrial function. Animal studies show increased pro-inflammatory biomarkers and DNA damage in aged endometrial cells. This persistent inflammation hampers endometrial receptivity and contributes to reproductive dysfunction.
Epigenetic Changes in the Endometrium
Epigenetic alterations, such as DNA methylation, play a significant role in aging. The concept of the epigenetic clock helps predict the biological age of tissues. Studies indicate that endometrial DNA methylation patterns change with age, affecting gene expression related to receptivity. Correcting for the menstrual phase can improve the accuracy of predicting endometrial age.
Impact of Advanced Age on Endometrial Receptivity
Oocyte donation cycles have been used to study the impact of age on endometrial receptivity. Results are mixed, with some studies indicating no significant effect of recipient age on implantation and pregnancy rates, while others suggest age-related impairments. Factors such as hormonal changes, cellular senescence, and epigenetic alterations collectively influence endometrial aging.
Future Directions
Future research should focus on understanding the molecular mechanisms of endometrial aging and developing targeted therapies, such as senolytic agents, to reverse age-related impairments. Prospective studies and clinical trials are needed to explore new therapeutic options and improve fertility outcomes for older women.
Conclusion
Maternal age significantly impacts female fertility by affecting both oocyte and endometrial quality. Advanced age is associated with hormonal fluctuations, cellular senescence, and epigenetic changes that impair endometrial receptivity. While medical advancements offer various strategies to address age-related fertility issues, further research is essential to develop effective treatments and improve reproductive success for women of advanced age.
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References
Pathare, A. D. S., Loid, M., Saare, M., Brusell Gidlöf, S., Zamani Esteki, M., Acharya, G., Peters, M., & Salumets, A. (2023). Endometrial receptivity in women of advanced age: an underrated factor in infertility. *Human Reproduction Update*, 29(6), 773–793. https://doi.org/10.1093/humupd/dmad019.
