# Association between PFAS compounds in follicular fluid and POR and the intervention effect of Qizi Yusi Tang: a study based on targeted PFAS quantification analysis

**Authors:** Hengbing Li, Jiacheng Li, Wenjing Jiang, Xin Hu, Zizhen Guo, Jingyan Song, Zhengao Sun

PMC · DOI: 10.3389/fendo.2026.1758118 · 2026-02-27

## TL;DR

This study finds that high levels of PFAS compounds, especially PFBA, in follicular fluid are linked to poor ovarian response in women with a specific TCM pattern, and that herbal treatment reduces these levels and improves outcomes.

## Contribution

The study identifies PFBA as a metabolic marker for Kidney Deficiency-Liver Stagnation Pattern poor ovarian response and shows that Qizi Yusi Tang herbal intervention reduces PFAS levels and improves clinical outcomes.

## Key findings

- Patients with Kidney Deficiency-Liver Stagnation Pattern POR had significantly higher PFBA levels in follicular fluid compared to controls.
- Qizi Yusi Tang intervention significantly reduced PFBA levels and improved ovarian response and embryo outcomes.
- Herbal treatment improved TCM syndrome scores and increased the number of oocytes and transferable embryos.

## Abstract

This study employs high-throughput targeted PFAS quantification analysis to analyze per- and polyfluoroalkyl substances (PFAS) metabolites in follicular fluid from women with Kidney Deficiency-Liver Stagnation Pattern poor ovarian response (POR) and IVF controls with normal ovarian reserve. Furthermore, we examine PFAS metabolite alterations in POR patients before and after intervention with kidney-tonifying and liver-soothing herbal medicine to suggest that PFAS compounds, particularly PFBA, are significant metabolic markers associated with the Kidney Deficiency-Liver Stagnation Pattern in POR.

This study enrolled 93 patients undergoing in vitro fertilization and embryo transfer (IVF-ET). Participants were divided into three groups: (1) the non-herbal intervention group (POR-NON group, n =31); (2) the control group (POR-CON group, n =31); and (3) the herbal medicine intervention group (POR-TCM, n =31). And ultra-high performance liquid chromatography-triple quadrupole mass spectrometer (UHPLC-QTRAP MS) was used to detect metabolites in the three groups of samples.

Patients with Kidney Deficiency-Liver Stagnation Pattern POR showed significantly higher levels of PFBA in follicular fluid compared to IVF controls with normal ovarian reserve (P < 0.01). The level of PFBA in follicular fluid was significantly lower in patients with Kidney Deficiency-Liver Stagnation Pattern POR who received QZYST intervention (POR-TCM group) than in those who did not receive intervention (POR-NON group) (P < 0.05). QZYST intervention significantly reduced Kidney Deficiency-Liver Stagnation Pattern scores in POR patients compared to both baseline (P < 0.001) and the POR-NON group (P < 0.05). The POR-TCM group demonstrated significantly improved number of oocytes retrieved (P < 0.05) and two-pronuclei (2PN) zygotes (P < 0.05), along with significantly fewer cycles with no transferable embryos (P < 0.05) compared to the POR-NON group.

Patients with Kidney Deficiency-Liver Stagnation Pattern POR exhibited significantly elevated levels of PFAS compounds in follicular fluid compared to IVF controls with normal ovarian reserve. Compared with the control group, patients who received QZYST intervention showed improvements in TCM syndrome manifestations and key clinical outcomes, and significantly lower PFBA levels were observed in the follicular fluid of the TCM intervention group than in those without intervention.

## Linked entities

- **Chemicals:** PFBA (PubChem CID 9777)

## Full-text entities

- **Genes:** GNRH1 (gonadotropin releasing hormone 1) [NCBI Gene 2796] {aka GNRH, GRH, LHRH, LNRH}, CGB5 (chorionic gonadotropin subunit beta 5) [NCBI Gene 93659] {aka CGB, HCG}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, PFAS (phosphoribosylformylglycinamidine synthase) [NCBI Gene 5198] {aka FGAMS, FGAR-AT, FGARAT, GATD8, PURL}, FABP3 (fatty acid binding protein 3) [NCBI Gene 2170] {aka FABP11, H-FABP, M-FABP, MDGI, O-FABP}, ACOT1 (acyl-CoA thioesterase 1) [NCBI Gene 641371] {aka ACH2, CTE-1, LACH2}, RICTOR (RPTOR independent companion of MTOR complex 2) [NCBI Gene 253260] {aka AVO3, PIA, hAVO3}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Il10 (interleukin 10) [NCBI Gene 25325] {aka IL10X, If2a}, FSHR (follicle stimulating hormone receptor) [NCBI Gene 2492] {aka FSHR1, FSHRO, LGR1, ODG1}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, AMH (anti-Mullerian hormone) [NCBI Gene 268] {aka MIF, MIS}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1) [NCBI Gene 5562] {aka AMPK, AMPK alpha 1, AMPKa1}, Sod2 (superoxide dismutase 2, mitochondrial) [NCBI Gene 20656] {aka MnSOD, Sod-2}, Cat (catalase) [NCBI Gene 12359] {aka 2210418N07, Cas-1, Cas1, Cs-1}, PPARA (peroxisome proliferator activated receptor alpha) [NCBI Gene 5465] {aka NR1C1, PPAR, PPAR-alpha, PPARalpha, hPPAR}, RPTOR (regulatory associated protein of MTOR complex 1) [NCBI Gene 57521] {aka KOG1, Mip1}, CYP19A1 (cytochrome P450 family 19 subfamily A member 1) [NCBI Gene 1588] {aka ARO, ARO1, CPV1, CYAR, CYP19, CYPXIX}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, ACOX1 (acyl-CoA oxidase 1) [NCBI Gene 51] {aka ACOX, AOX, MITCH, PALMCOX, SCOX}, RHCG (Rh family C glycoprotein) [NCBI Gene 51458] {aka C15orf6, PDRC2, RHGK, SLC42A3}, Keap1 (kelch-like ECH-associated protein 1) [NCBI Gene 50868] {aka INRF2, mKIAA0132}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, CROT (carnitine O-octanoyltransferase) [NCBI Gene 54677] {aka COT}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Hmox1 (heme oxygenase 1) [NCBI Gene 15368] {aka D8Wsu38e, HO-1, HO1, Hemox, Hmox, Hsp32}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}
- **Diseases:** IVF (MESH:C537182), autoimmune (MESH:D001327), infections (MESH:D007239), HIV/HBV (MESH:D006509), ET (MESH:D016751), dizziness (MESH:D004244), chromosomal abnormalities (MESH:D002869), syphilis (MESH:D013587), AFC (MESH:D000072717), premature ovarian insufficiency (MESH:D016649), Congenital reproductive tract anomalies (MESH:D060737), menopausal syndrome (MESH:D008594), hemolysis (MESH:D006461), viral infections (MESH:D014777), chronic depression (MESH:D003866), chromosomal misalignment (MESH:D017760), ulcerative colitis (MESH:D003093), luteal phase (MESH:D000210), fibrosis (MESH:D005355), loss of libido (MESH:D016388), insomnia (MESH:D007319), PDA (MESH:D011015), soreness (MESH:D063806), hepatorenal damage (MESH:D006530), irritability (MESH:D001523), granulosa-like tumor (MESH:D006106), hepatomegaly (MESH:D006529), pelvic inflammatory disease (MESH:D000292), TCM (MESH:C562377), aneuploidy (MESH:D000782), Liver Stagnation (MESH:D017093), Impaired ovarian reserve (MESH:D010049), hypochondriac distension (MESH:D006998), soreness in lumbar (MESH:C563613), Environmental Endocrine Disruptors (MESH:D018876), HCV (MESH:D006526), fatigue (MESH:D005221), systemic illnesses (MESH:D012140), Kidney Deficiency (MESH:D007680), OHSS (MESH:D016471), weakness (MESH:D018908), pain (MESH:D010146), amenorrhea (MESH:D000568), toxicity (MESH:D064420), hypoxic (MESH:D002534), cardiovascular/hepatic/renal/hematopoietic (MESH:D019337), tinnitus (MESH:D014012), mitochondrial defects (MESH:C565376), inflammatory cytokines (MESH:D000080424), actin dysfunction (MESH:C564942), Infertility (MESH:D007246), inflammation (MESH:D007249), TCM syndrome (MESH:D013577), Kidney Deficiency-Liver (MESH:D051437), male-factor infertility (MESH:D007248), Hypersensitivity (MESH:D004342), abortion (MESH:D000026), breast distension (MESH:D061325), hot (MESH:D019584), endocrine disruptors (MESH:D004700)
- **Chemicals:** verbascoside (MESH:C058956), ROS (MESH:D017382), E2 (MESH:D004958), PFNA (MESH:C101816), NON (-), calcium phosphate (MESH:C020243), LH (MESH:D007986), calcium (MESH:D002118), curcumin (MESH:D003474), Acetonitrile (MESH:C032159), iridoid glycosides (MESH:D057889), follicle-stimulating hormone (MESH:D005640), amino acids (MESH:D000596), ecliptasaponin A (MESH:C000611296), terpenoids (MESH:D013729), Ammonium hydroxide (MESH:D064753), salidroside (MESH:C009172), carbon (MESH:D002244), Methanol (MESH:D000432), Heptafluorobutyric acid (MESH:C033094), carbohydrates (MESH:D002241), vinegar (MESH:D019342), triterpenoids (MESH:D014315), curzerene (MESH:C000609675), progesterone (MESH:D011374), echinacoside (MESH:C060297), MDA (MESH:D015104), PFOA (MESH:C023036), flavonoids (MESH:D005419), cyclophosphamide (MESH:D003520), 5-HMF (MESH:C008046), PFUnDA (MESH:C586085), ammonia (MESH:D000641), Per- and polyfluoroalkyl substances (MESH:D005466), HMG (MESH:D008596), specnuezhenide (MESH:C083178), CCl4 (MESH:D002251), lipid (MESH:D008055), nitrogen (MESH:D009584), PFOS (MESH:C076994), D-galactose (MESH:D005690), Curcuminoids (MESH:D036381), calcium carbonate (MESH:D002119), Ammonium acetate (MESH:C018824), DHT (MESH:D013196), PDA (MESH:C036567), water (MESH:D014867), P (MESH:D010758)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Cistanche deserticola (species) [taxon 161395], Rattus norvegicus (brown rat, species) [taxon 10116], Danio rerio (leopard danio, species) [taxon 7955], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** KGN — Homo sapiens (Human), Ovarian granulosa cell tumor, Cancer cell line (CVCL_0375)

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12982041/full.md

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Source: https://tomesphere.com/paper/PMC12982041