Details zur Publikation |
| Kategorie | Textpublikation |
| Referenztyp | Zeitschriften |
| DOI | 10.1093/humrep/deag083.707 |
| Titel (primär) | Effects of real-life PFAS mixture on endometrial hormone signaling: insights from endometrial organoids |
| Autor | Xia, Y.; Voss, H.; Fest, S.; Zenclussen, A.C.; Stojanovska, V. |
| Quelle | Human Reproduction |
| Erscheinungsjahr | 2026 |
| Department | IMMU |
| Band/Volume | 41 |
| Heft | Suppl. 1 |
| Seite von | deag083.707 |
| Sprache | englisch |
| Topic | T9 Healthy Planet |
| Abstract | Study question Do real-life PFAS mixtures interfere with the hormone-mediated response in hormone responsive endometrial organoids? Summary answer PFAS mixture decreased estrogen receptor alpha and progesterone receptor expression and weakened hormone dependent transcriptional responses in both proliferative and secretory phase endometrial organoids. What is known already Female fertility depends on the precise coordinated response of the endometrium to estrogen and progesterone through an integrated network of hormone receptors. The normal expression and signaling of receptors not only regulate the cyclical proliferation and differentiation of the endometrium but also directly influence the success of embryo implantation. Endocrine disrupting chemicals have raised concern because they can interfere with hormone signaling. Among them, PFAS are environmentally persistent, bioaccumulative and globally detected in the general population worldwide. Accumulating evidence suggests that PFAS exposure is associated with infertility and other gynecological disorders, thereby imposing an increasing economic and clinical burden worldwide. Study design, size, duration This experimental in vitro study used endometrial organoids derived from nine donors. Organoids were hormonally differentiated to model proliferative and secretory phases and exposed to real-life PFAS mixtures for six days. Participants/materials, setting, methods Endometrial organoids were derived from elective terminations of pregnancy. Organoids were induced with estrogen and progesterone to model the proliferative and secretory endometrial phases. Organoids from both phases were exposed for 6 days to a real-life PFAS mixture at 0.01, 1, and 10 µM. Mifepristone (0.5 µM) and fulvestrant (10 µM) were used as controls. Estrogen and progesterone receptor–related effects were assessed using gene expression analysis and immunofluorescence staining. Main results and the role of chance We successfully established in vitro endometrial hormone-responsive organoids that model the proliferative and secretory phases of the endometrium, by showing temporal receptor expression of the progesterone receptor. Following 6 days of exposure with the PFAS mixture during the proliferative phase, reduced estrogen receptor alpha (ERα) and progesterone receptor immunofluorescence intensities were registered in the endometrial organoids. This was followed by a decreased ESR1 and PGR gene expression. In contrast, exposure of the endometrial organoids in the secretory phase to PFAS mixture lead to reduced ERα and PR immunofluorescence intensities and decreased PGR gene expression, while ESR1 gene expression remained unaffected. Limitations, reasons for caution The study used an in vitro organoid system and a limited donor number. Systemic metabolism and long-term exposure were not modeled. Wider implications of the findingsThis study provides valuable insights into the negative impact of a real-life PFAS mixture on the hormone mediated response in the endometrium. Our findings highlight the importance of considering PFAS exposure when evaluating reproductive health outcomes. |
| Xia, Y., Voss, H., Fest, S., Zenclussen, A.C., Stojanovska, V. (2026): Effects of real-life PFAS mixture on endometrial hormone signaling: insights from endometrial organoids Hum. Reprod. 41 (Suppl. 1), deag083.707 10.1093/humrep/deag083.707 |
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