PCOS: What Causes It?
Although the exact cause of PCOS is still not fully understood, research suggests that it actually begins in the womb. To understand this, we have to dive into the fascinating world of epigenetics. Epigenetics is all about how our environment and behaviors can influence our genes, and PCOS is a perfect example of these epigenetic changes being passed from mother to baby.
When a female fetus is exposed to high levels of testosterone or anti-Müllerian hormone (AMH) during development, usually because the mother herself has PCOS, it triggers changes in specific genes associated with PCOS. These changes occur due to the influence of the environment within the womb, and that’s where the journey of PCOS begins.
While there are various genetic changes that have been implicated as being associated with the development of PCOS, one in particular has received the most attention. This significant genetic change is related to an enzyme called P450c17. This enzyme plays a crucial role in regulating testosterone production by controlling 17-hydroxylase and 17,20-lyase activities, two enzymes involved in androgen production.
Picture P450c17 as a traffic control officer for testosterone levels. In women without PCOS, this officer efficiently slows down testosterone production, ensuring it doesn’t go overboard. However, in women with PCOS, it’s like there’s no traffic control officer at all. This enzyme works tirelessly, producing excessive amounts of testosterone round the clock. What’s more, when insulin levels are high, this enzyme goes into overdrive and produces even more testosterone. This genetic change involving P450c17 is one of the key factors that contribute to PCOS, shifting it from regulated traffic to a nonstop green light!
Normal
PCOS
Experts have revealed that the genetic changes associated with PCOS can actually be passed down for multiple generations, with studies showing the genes spanning at least three generations in mice. This means that a mom with PCOS might unknowingly be passing down the condition to her grandchildren or even her great-grandchildren.
This discovery sheds light on why daughters born to mothers with PCOS have a 5-fold increased risk of developing PCOS themselves. In fact, a whopping 70% of daughters born to women with PCOS will also experience this condition. These genetic changes don’t just affect females. Even male children born to women with PCOS have been shown to have poorer metabolic health and hormonal imbalance later in life.
So, what can we do about it? Well, it turns out that maintaining lower insulin levels before and during pregnancy is key. By keeping insulin levels within the normal range (3-8 mIU/mL), we can help regulate testosterone levels and prevent these epigenetic changes from occurring in the offspring. Understanding these genetic changes that lead to PCOS empowers us to explore interventions and lifestyle strategies that can effectively manage the condition. By targeting insulin levels through adopting a low insulin lifestyle, women with PCOS can take charge of their health and the health of future generations.
References
- Zhu Z, Cao F, Li X. Epigenetic Programming and Fetal Metabolic Programming. Front Endocrinol (Lausanne). 2019;10. doi:10.3389/fendo.2019.00764
- Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R. Polycystic ovary syndrome: Etiology, pathogenesis and diagnosis. Nat Rev Endocrinol. 2011;7(4). doi:10.1038/nrendo.2010.217
- Hoeger KM, Dokras A, Piltonen T. Update on PCOS: Consequences, Challenges, and Guiding Treatment. J Clin Endocrinol Metab. 2021;106(3):e1071-e1083. doi:10.1210/clinem/dgaa839
- Qin K nan, Rosenfield RL. Role of cytochrome P450c17 in polycystic ovary syndrome. Mol Cell Endocrinol. 1998;145(1-2):111-121. doi:10.1016/S0303-7207(98)00177-4
- Bell GA, Sundaram R, Mumford SL, et al. Maternal polycystic ovarian syndrome and early offspring development. Human Reproduction. 2018;33(7):1307-1315. doi:10.1093/humrep/dey087
- Şanlı E, Kabaran S. Maternal Obesity, Maternal Overnutrition and Fetal Programming: Effects of Epigenetic Mechanisms on the Development of Metabolic Disorders. Curr Genomics. 2019;20(6):419-427. doi:10.2174/1389202920666191030092225
- Pohlmeier AM, Phy JL, Watkins P, et al. Effect of a low-starch/low-dairy diet on fat oxidation in overweight and obese women with polycystic ovary syndrome. Applied Physiology, Nutrition and Metabolism. 2014;39(11):1237-1244. doi:10.1139/apnm-2014-0073
- Phy Jennifer L, Pohlmeier AM, Cooper JA, et al. Low Starch/Low Dairy Diet Results in Successful Treatment of Obesity and Co- Morbidities Linked to Polycystic Ovary Syndrome (PCOS). J Obes Weight Loss Ther. 2015;05(02). doi:10.4172/2165-7904.1000259
