Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, and a growing line of research links part of its ovarian damage to endoplasmic reticulum (ER) stress in granulosa cells, the cells that surround and support each developing egg. TUDCA keeps appearing in that research because it is the ER stress inhibitor most labs reach for. In a mouse model of PCOS, TUDCA reduced ovarian fibrosis and collagen deposition [1]. In another, it reduced granulosa cell death [2] and improved the estrous cycle [3]. Those are interesting results. They are also mouse and cell culture results, and no trial has given TUDCA to women with PCOS. This page goes through what was found, what the mouse model is, and why the gap between the two matters especially for a condition so closely tied to fertility.
Key Takeaways
- ER stress is activated in granulosa cells from women with PCOS and in a PCOS mouse model [1], and androgens appear to be one driver [2].
- In dehydroepiandrosterone (DHEA)-induced PCOS mice, TUDCA decreased ovarian interstitial fibrosis and collagen [1], reduced granulosa cell apoptosis [2], and improved the estrous cycle with fewer atretic follicles [3].
- In cultured granulosa cells, TUDCA blocked testosterone-induced apoptosis [2], ferroptosis [4] and pyroptosis [5], and restored autophagy after palmitic acid exposure [6].
- Granulosa cells taken from women with PCOS during IVF showed less apoptosis and higher progesterone and estrogen output after TUDCA treatment in culture [7].
- No clinical trial has tested TUDCA in women with PCOS, and TUDCA has not been established as safe in pregnancy.
Why ER Stress Is Studied in PCOS
Granulosa cells line the follicle, the fluid-filled sac in which an egg matures. They produce hormones, including estrogen and progesterone, and they make a large amount of protein to do it. Cells with heavy protein workloads depend on the endoplasmic reticulum to fold those proteins correctly, and when folding falls behind, they switch on a stress program called the unfolded protein response. If that response stays on, it can push the cell toward death.
In 2017, a research group reported that ER stress was activated in granulosa cells from PCOS patients and in a well-established mouse model of PCOS [1]. They also found that forcing ER stress in human granulosa cells raised pro-fibrotic growth factors including TGF-β1, and that these factors were also raised in granulosa cells from PCOS patients [1]. That made ER stress a candidate link between the hormonal features of PCOS and the scarring and follicle problems seen in the ovary.
What TUDCA Did in PCOS Mice
Most of the animal work uses the DHEA-induced mouse model, in which mice are given the androgen precursor DHEA to reproduce some PCOS features. It is a useful model of androgen excess, but it is not the same as the human condition, which has several subtypes and a strong metabolic component.
Fibrosis. In the 2017 study, treating PCOS mice with TUDCA or a second ER stress inhibitor, BGP-15, decreased interstitial fibrosis and collagen deposition in the ovaries and lowered TGF-β1 in granulosa cells [1].
Granulosa cell death. A 2019 study from the same field tested whether androgens drive ER stress and apoptosis [2]. Testosterone switched on several unfolded protein response genes, including CHOP, and a death receptor called DR5 in cultured human granulosa-lutein cells. Pretreatment with TUDCA blocked testosterone-induced apoptosis along with the rise in DR5 and CHOP. DR5 and CHOP were also raised in granulosa cells from PCOS patients and from PCOS mice, and treating PCOS mice with TUDCA reduced granulosa cell apoptosis and DR5 expression in antral follicles [2].
Glycation and the estrous cycle. A 2020 follow-up found that testosterone increased the receptor for advanced glycation end products (RAGE) and the build-up of these products in granulosa cells, and that TUDCA pretreatment reduced both [3]. In PCOS mice, either a RAGE inhibitor or TUDCA reduced RAGE expression and glycation products in granulosa cells, improved the estrous cycle and reduced the number of atretic antral follicles [3]. The paper described TUDCA as an ER stress inhibitor in clinical use. That phrase does not mean it is approved or tested as a PCOS treatment.
The Cell Studies: Three Kinds of Cell Death
Later studies widened the picture by looking at other ways granulosa cells can die. In a human granulosa cell line called KGN, testosterone raised oxidative stress, lipid peroxidation and iron build-up, which are the signatures of ferroptosis, and TUDCA significantly mitigated testosterone-induced ferroptosis [4]. Ferroptosis and ER stress were also activated in granulosa cells from women with PCOS undergoing IVF and in PCOS-like mice [4].
A 2023 study measured higher levels of the inflammatory signals IL-1β, IL-8, IL-17 and IL-18 in follicular fluid from PCOS patients with high androgen levels, and found more pyroptosis, an inflammatory form of cell death, in their granulosa cells [5]. In testosterone-treated KGN cells, TUDCA reduced the inflammatory markers and pyroptosis. Suppressing inflammation with a different compound lowered pyroptosis without changing ER stress sensors, which led the authors to place ER stress upstream of the inflammation [5].
Palmitic acid, a saturated fatty acid, is often raised in the blood and follicular fluid of women with PCOS. In KGN cells, palmitic acid activated the IRE1 branch of the ER stress response, suppressed autophagy and impaired mitochondrial function, and TUDCA reduced IRE1 activation and restored autophagy and mitochondrial function [6].
The Closest Thing to Human Data
One study used granulosa cells from 116 patients undergoing IVF or ICSI [7]. Granulosa cells from women with PCOS showed a higher apoptosis rate, lower progesterone and estrogen output in culture, and higher expression of the ER stress genes XBP1(s), ATF6 and CHOP. When those cells were treated with TUDCA in culture, apoptosis and ER stress markers fell, and progesterone and estrogen output rose [7].
That is human tissue, but it is still a dish. The cells were removed during an IVF procedure and treated outside the body. Nobody in the study took TUDCA, and the result does not show whether an oral dose would reach the ovary, change hormone levels, restore ovulation or affect pregnancy rates.
The Gut Bile Acid Connection, and What It Does Not Show
A 2019 Nature Medicine paper found that women with PCOS had more of the gut bacterium Bacteroides vulgatus and lower levels of two bile acids, glycodeoxycholic acid and tauroursodeoxycholic acid [8]. Transplanting fecal microbiota from women with PCOS into mice disrupted ovarian function and caused insulin resistance and infertility. The mechanism the authors worked out ran through glycodeoxycholic acid, which raised intestinal IL-22, and IL-22 improved the PCOS phenotype [8].
It is easy to turn this into a claim that women with PCOS are low in TUDCA and should replace it. The study does not support that step. It measured lower TUDCA as part of a changed bile acid profile, and it tested glycodeoxycholic acid and IL-22, not TUDCA supplementation. It is a reason to keep studying bile acids in PCOS, not evidence for a supplement.
Why Caution Matters More Here
PCOS is a condition many people manage while trying to conceive, which raises the stakes on any untested supplement. TUDCA has not been established as safe in pregnancy or while trying to conceive, and the research above gives no information about effects on an embryo or a pregnancy in people. The mouse results also come from a single induced model that captures androgen excess but not the full range of PCOS.
PCOS has evidence-based care for its main problems, including cycle regulation, ovulation induction, insulin resistance and the long-term metabolic risks. If you are interested in where ER stress research may go, it is reasonable to ask your gynecologist or reproductive endocrinologist about it. It is not a reason to start TUDCA on your own, and especially not during fertility treatment or once pregnancy is possible.
Bottom Line
ER stress is active in granulosa cells from women with PCOS [1], and in DHEA-induced PCOS mice TUDCA reduced ovarian fibrosis [1], granulosa cell apoptosis [2] and estrous cycle disruption [3]. In cultured cells it eased several forms of cell death [4] [5], and in granulosa cells taken during IVF it lowered apoptosis and raised hormone output [7]. No woman with PCOS has taken TUDCA in a published trial, and pregnancy safety is unknown. For now this is a research direction, not a treatment.
Frequently Asked Questions
Does TUDCA help PCOS?
It has not been tested in women with PCOS. In PCOS mice, TUDCA reduced ovarian fibrosis [1], granulosa cell death [2] and improved the estrous cycle [3], but those are animal results from one induced model.
Can TUDCA improve fertility in PCOS?
There is no evidence in people. TUDCA reduced apoptosis and raised hormone output in granulosa cells removed during IVF and treated in a dish [7], but no study has measured ovulation or pregnancy in women taking it, and its safety in pregnancy has not been established.
Are women with PCOS low in TUDCA?
One study found lower gut levels of TUDCA and glycodeoxycholic acid in women with PCOS, but the mechanism it tested ran through glycodeoxycholic acid and IL-22, not TUDCA [8]. It does not show that taking TUDCA corrects anything.
References
- Takahashi N, et al. Activation of Endoplasmic Reticulum Stress in Granulosa Cells from Patients with Polycystic Ovary Syndrome Contributes to Ovarian Fibrosis. Scientific Reports (2017). PMID 28883502
- Azhary JMK, et al. Endoplasmic Reticulum Stress Activated by Androgen Enhances Apoptosis of Granulosa Cells via Induction of Death Receptor 5 in PCOS. Endocrinology (2019). PMID 30423122
- Azhary JMK, et al. Androgens Increase Accumulation of Advanced Glycation End Products in Granulosa Cells by Activating ER Stress in PCOS. Endocrinology (2020). PMID 32020188
- Ding H, et al. Endoplasmic reticulum stress-mediated ferroptosis in granulosa cells contributes to follicular dysfunction of polycystic ovary syndrome driven by hyperandrogenism. Reproductive BioMedicine Online (2024). PMID 39024925
- Xiang Y, et al. Hyperandrogenism drives ovarian inflammation and pyroptosis: A possible pathogenesis of PCOS follicular dysplasia. International Immunopharmacology (2023). PMID 37918087
- Cao M, et al. Tauroursodeoxycholic acid ameliorates palmitic acid induced endoplasmic reticulum stress and impaired autophagy via IRE1- XBP1-FoxO1 pathway in KGN cells. Biochemical Pharmacology (2025). PMID 41043520
- Sun HL, et al. Does endoplasmic reticulum stress stimulate the apoptosis of granulosa cells in polycystic ovary syndrome? Journal of Physiology and Pharmacology (2021). PMID 35288480
- Qi X, et al. Gut microbiota-bile acid-interleukin-22 axis orchestrates polycystic ovary syndrome. Nature Medicine (2019). PMID 31332392
These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease.
These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure, or prevent any disease. Content is for informational purposes only and is not medical advice; consult a qualified healthcare provider before starting any supplement. As an Amazon Associate we earn from qualifying purchases.