Could We Really Save The Fertility Crisis?
Written by Laurel Geraci
Edited by Connie Quan
Jan 23rd 2022
Edited by Connie Quan
Jan 23rd 2022
With the rise of modern day medicine, food, and water accessibility, it’s no wonder that our current life expectancy is 40 years longer than it was 150 years ago. While this is certainly a statistic worth celebrating, the sad fact is that the age at which natural menopause (ANM) begins has not changed much. With our society progressing towards starting a family later in life, freezing eggs seems like a viable option to keep the “good” eggs alive-yet the likelihood of achieving pregnancy with thawed eggs is only 6.5% (Argyle et al.). So how can we combat the ANM to preserve fertility?
Scientists Ruth et al. might have the answer. The first part is understanding the genetics behind fertility issues. To begin with, they hypothesized that the biological pathway with the strongest effect on ANM and reproductive aging is the DNA damage response (DDR) pathway. This pathway contains genes that are necessary for recognizing and responding to different types of DNA damage, including the degradation of oocytes or eggs (Pilié et al.). Starting with a genome-wide association study (GWAS) that uses data from 23andMe, the researchers found that heritability can make up for about 31-38% of the differences we see in ANM based on women aged 40-60 (Ruth et al.). Prior to age 40, they looked at the results of a polygenic score, which quantifies how genetic variation might affect a person’s physical characteristics like ANM. Not only were these scores able to determine women with high risks of developing premature ovarian insufficiency, but they also observed that biological processes are shared in both these clinical extremes and in normal reproductive aging patterns. Overall, it seems that ANM can be observed through gene expression in reproductive tissues.
The second part requires us to look at model organisms that share enough of our genes for the research to be relevant. Scientists have been able to figure out a lot about reproductive lifespan by looking at mice in particular. In a previous study done by Aiken et al., researchers discovered that female mice consuming fattening diets during their pregnancy decreased the amount of oocytes in their offspring (Aiken et al.). Looking more closely at this phenomena, Ruth et al. observed variable expression in 2 key ovarian genes of the offspring: Dmc1 and Brsk1. Dmc1 is known for recombining chromosomes during meiosis, while Brsk1 serves as a DNA damage sensor. Since the diets of the female mice were manipulated, we can conclude that in utero, maternal diet caused these changes in DDR genes responsible for reproductive shelflife. Finally, in vitro studies of a third gene called Chek2, which acts to remove damaged oocytes, show that mutants with an inactive version of the gene have reduced oocyte loss without compromising mother or offspring wellbeing later on. Ruth et al. suggest that this locus in the genome could be used in future IVF treatments to temporarily prolong ovarian function and preservation.
There are undoubtedly high hopes for improving the fertility crisis. Like many discoveries in the biological field, this discovery is another classic example of epigenetics. Until IVF treatments with gene therapy are widely available, the best recommendations for soon-to-be parents are to take proper care of their diet and physical state. Not only will this contribute to their child’s health, but it will also promise many more years to spend with them.
References
- Aiken, C. E., Tarry-Adkins, J. L., Penfold, N. C., Dearden, L., & Ozanne, S. E. (2016). Decreased ovarian reserve, dysregulation of mitochondrial biogenesis, and increased lipid peroxidation in female mouse offspring exposed to an obesogenic maternal diet. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 30(4), 1548–1556. https://doi.org/10.1096/fj.15-280800
- Argyle, C. E., Harper, J. C., & Davies, M. C. (2016). Oocyte cryopreservation: where are we now?. Human reproduction update, 22(4), 440–449. https://doi.org/10.1093/humupd/dmw007
- Pilié, P. G., Tang, C., Mills, G. B., & Yap, T. A. (2019). State-of-the-art strategies for targeting the DNA damage response in cancer. Nature reviews. Clinical oncology, 16(2), 81–104. https://doi.org/10.1038/s41571-018-0114-z
- Ruth, K. S., Day, F. R., Hussain, J., Martínez-Marchal, A., Aiken, C. E., Azad, A., Thompson, D. J., Knoblochova, L., Abe, H., Tarry-Adkins, J. L., Gonzalez, J. M., Fontanillas, P., Claringbould, A., Bakker, O. B., Sulem, P., Walters, R. G., Terao, C., Turon, S., Horikoshi, M., Lin, K., … Perry, J. (2021). Genetic insights into biological mechanisms governing human ovarian ageing. Nature, 596(7872), 393–397. https://doi.org/10.1038/s41586-021-03779-7
Image Source: “Close-up pregnant woman's belly on white background. Pregnancy, parenthood, preparation and expectation concept” by Marco Verch licensed under CC BY 2.0