Estrogen receptor-dependent mechanisms underlying DES promoted endometrial carcinoma: Study in vivo
4 affiliations
- 1Doctoral Program of Medical Science, Medical Faculty, Universitas Airlangga, Surabaya, Indonesia; Corresponding author.
- 2Department of Obstetrics and Gynecology, Medical Faculty, Universitas Airlangga, Surabaya, Indonesia; Department of Obstetrics and Gynecology, Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
- 3Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan
- 4Department of Veterinary Medical Science, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia
Abstract
Background: Diethylstilbestrol (DES) is a potent synthetic estrogen implicated in endometrial carcinogenesis through estrogen receptor (ER)-dependent mechanisms. However, the temporal relationship between DES exposure, estrogen receptor alpha (ERα) expression, and histopathological progression of endometrial lesions remains incompletely defined in vivo. Methods: An experimental in vivo study was conducted using 32 eight-week-old female mice randomly assigned to eight groups, including two untreated controls and six DES-treated groups with varying exposure and observation durations. DES was administered at 1000 µg according to predefined schedules. Uterine tissues were examined histopathologically using HE staining, and ERα expression was evaluated by immunohistochemistry using the modified Remmele Immunoreactive Score. Statistical analyses included one-way ANOVA with Tukey post hoc testing, Kruskal–Wallis and Mann–Whitney U tests, and path analysis to assess mechanistic relationships. Results: ERα expression differed significantly among groups, with the highest expression observed in mice receiving prolonged DES exposure followed by extended observation. Histopathological evaluation demonstrated a clear progression from normal endometrium in control groups to higher-grade lesions in DES-treated groups, with severe (Grade 3) changes predominating in high exposure cohorts. Path analysis revealed a significant association between DES exposure and ERα expression, as well as a positive effect of ERα on EC development. Conclusions: DES promotes endometrial carcinogenesis through ERα dependent mechanisms in vivo. Increased ERα expression parallels histopathological progression, and mechanistic analysis confirms ERα as a key mediator linking synthetic estrogen exposure to tumor development. These findings underscore the central role of estrogen signaling in DES-induced EC.
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BibTeX
@article{waluyo2026estrogen,
title = {{Estrogen receptor-dependent mechanisms underlying DES promoted endometrial carcinoma: Study in vivo}},
author = {Setyo Teguh Waluyo and Brahmana Askandar Tjopkroprawiro and Peng-Hui Wang and Widjiati Widjiati},
journal = {European Journal of Obstetrics \& Gynecology and Reproductive Biology: X},
year = {2026},
month = oct,
doi = {10.1016/j.eurox.2026.100504},
url = {https://doi.org/10.1016/j.eurox.2026.100504},
note = {CC BY},
}
RIS
TY - JOUR
TI - Estrogen receptor-dependent mechanisms underlying DES promoted endometrial carcinoma: Study in vivo
AU - Setyo Teguh Waluyo
AU - Brahmana Askandar Tjopkroprawiro
AU - Peng-Hui Wang
AU - Widjiati Widjiati
PY - 2026
DA - 2026/10/17
JO - European Journal of Obstetrics & Gynecology and Reproductive Biology: X
DO - 10.1016/j.eurox.2026.100504
UR - https://doi.org/10.1016/j.eurox.2026.100504
AB - Background: Diethylstilbestrol (DES) is a potent synthetic estrogen implicated in endometrial carcinogenesis through estrogen receptor (ER)-dependent mechanisms. However, the temporal relationship between DES exposure, estrogen receptor alpha (ERα) expression, and histopathological progression of endometrial lesions remains incompletely defined in vivo. Methods: An experimental in vivo study was conducted using 32 eight-week-old female mice randomly assigned to eight groups, including two untreated controls and six DES-treated groups with varying exposure and observation durations. DES was administered at 1000 µg according to predefined schedules. Uterine tissues were examined histopathologically using HE staining, and ERα expression was evaluated by immunohistochemistry using the modified Remmele Immunoreactive Score. Statistical analyses included one-way ANOVA with Tukey post hoc testing, Kruskal–Wallis and Mann–Whitney U tests, and path analysis to assess mechanistic relationships. Results: ERα expression differed significantly among groups, with the highest expression observed in mice receiving prolonged DES exposure followed by extended observation. Histopathological evaluation demonstrated a clear progression from normal endometrium in control groups to higher-grade lesions in DES-treated groups, with severe (Grade 3) changes predominating in high exposure cohorts. Path analysis revealed a significant association between DES exposure and ERα expression, as well as a positive effect of ERα on EC development. Conclusions: DES promotes endometrial carcinogenesis through ERα dependent mechanisms in vivo. Increased ERα expression parallels histopathological progression, and mechanistic analysis confirms ERα as a key mediator linking synthetic estrogen exposure to tumor development. These findings underscore the central role of estrogen signaling in DES-induced EC.
SN - 2590-1613
ER -