The female reproductive system is one of the first systems in the human body to show signs of aging.1 However, this aging process albeit natural and inevitable often results in reduced fertility among other reproductive challenges. As a woman ages, her ovaries experience significant changes. These changes include a reduction in the number of eggs in her ovaries as well as a decline in their quality.
Furthermore, the aging process is also associated with hormonal fluctuations that disrupt and eventually result in a complete cessation of her cycles. Together, these factors account for the reduced fertility and other age-related reproductive challenges women face. Expectedly, these transformations can lead to emotional stress and uncertainty around family planning for any woman who has begun to experience them.
Thankfully, however, recent research has proposed a new perspective on this aging phenomenon suggesting that it may be possible to mitigate some of the effects associated with ovarian aging and thus prolong female fertility.
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Understanding Ovarian Aging: The Role of Inflammation in Ovarian Aging
Table of Contents
Inflammation plays a pivotal role in the aging process of the ovaries in every woman. This complex biological response is part of the human body’s defense mechanism and is designed to eliminate harmful stimuli and initiate healing. However, when inflammation becomes chronic, it can lead to detrimental effects on the organ affected.
In the context of ovarian aging, each month, the rupture of the ovarian follicles and release of egg from the ovaries is associated with some degree of trauma. Consequently, localized inflammation in the ovaries occurs as the body aims to repair the damaged ovaries. Over time, a chronic form of inflammation sets in, and its progression is influenced by factors including estrogen levels, diet, and lifestyle choices.
Targeting Chronic Inflammation Improves Ovarian Function
Understanding the influence of chronic inflammation on ovarian function, the researchers investigated two drugs that act by inhibiting chronic inflammatory processes. These drugs included Etanercept and Pirfenidone. Pharmacologically, Etanercept inhibits inflammation through blocking receptors known as TNF-alpha receptors found on the surface of cells. Pirfenidone on the other hand prevents the formation of fibrous tissue which is the hallmark of chronic inflammation.
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In their study, however, the researchers observed that pirfenidone influenced the expression of genes involved in the inflammatory process. According to their study findings, pirfenidone significantly reduced Col1a1, a gene needed for collagen production. This is significant because collagen is an important component of the fibrotic tissue observed in chronic inflammation.
Remarkably, they noted that systemic delivery of pirfenidone via mini-osmotic pumps into mice for 6 weeks reduced age-related increase in ovarian fibrosis without affecting other health parameters. Moreover, not only was there a downregulation of inflammatory genes with pirfenidone, but also genes related to reproductive function were noted to be increased. Consequently, mice treated with pirfenidone demonstrated increased follicle and corpora lutea numbers.
On the other hand, they reported that etanercept had no influence on TNF genes.
Clinical Significance: Implications for Women’s Health
Given the important role of the inflammatory process in age-related ovarian decline, the study demonstrates the potential benefit of pirfenidone in preventing and treating fertility issues arising in women as they age. It is important to note that although pirfenidone is an FDA-approved drug for idiopathic pulmonary fibrosis, its clinical usefulness in humans for age-related ovarian decline is still untested. Further research demonstrating its usefulness in humans is therefore necessary.
References
Amargant, F., Vieira, C., Pritchard, M. T., & Duncan, F. E. (2024). Systemic low-dose anti-fibrotic treatment attenuates ovarian aging in the mouse [Preprint]. bioRxiv. https://doi.org/10.1101/2024.06.21.600035
Pataky, M. W., Young, W. F., & Nair, K. S. (2021). Hormonal and metabolic changes of aging and the influence of lifestyle modifications. Mayo Clinic Proceedings, 96(3), 788–814.
https://doi.org/10.1016/j.mayocp.2020.12.033
Chen, L., Deng, H., Cui, H., Fang, J., Zuo, Z., Deng, J., Li, Y., Wang, X., & Zhao, L. (2018). Inflammatory responses and inflammation-associated diseases in organs. Oncotarget, 9(6), 7204–7218.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805548/
Pan A, Gerriets V. Etanercept. [Updated 2023 Jul 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK545252/
Aimo, A., Spitaleri, G., Nieri, D., Tavanti, L. M., Meschi, C., Panichella, G., Lupón, J., Pistelli, F., Carrozzi, L., Bayes-Genis, A., & Emdin, M. (2022). Pirfenidone for idiopathic pulmonary fibrosis and beyond. Cardiac Failure Review, 8, e12. https://doi.org/10.15420/cfr.2021.30
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