Vitamin D3 promotes regression of endometrial implants comparable to buserelin in a rat model of endometriosis

article OA: closed public-domain-us
AI-generated summary by claude@2026-07, 2026-07-28

Vitamin D3 treatment in a rat endometriosis model reduced endometrial implant size and adhesions, inducing apoptosis similarly to buserelin.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Abstract

Buserelin, a gonadotropin-releasing hormone agonist, reduces gonadotropin and estrogen levels and is commonly used to alleviate the symptoms of endometriosis. Vitamin D3 has been reported to exhibit anti-inflammatory and pro-apoptotic properties, which may contribute to the regression of endometrial lesions. We aimed to investigate the effects of vitamin D3 on the regression and recurrence prevention of endometrial implant sites through the induction of apoptosis comparable to buserelin acetate in an experimental rat endometriosis model. Endometrial implant size and adhesion scores were evaluated following treatment. Microscopic analyses were performed using hematoxylin-eosin-stained preparations. Apoptotic activity was assessed by TUNEL assay, along with the expression of Bcl-2 and Bax antibodies. Untreated rats exhibited larger implant volumes, severe glandular and stromal alterations, and pronounced inflammatory infiltration. In contrast, vitamin D3 and buserelin treatments reduced implant size and adhesion scores. The vitamin D3-treated group demonstrated a high density of TUNEL-positive cells. Increased expression of Bcl-2 protein was found in untreated groups whereas, increased expression of Bax protein was found in both treated groups. In conclusion, vitamin D₃ may have contributed to the regression of endometrial implants, possibly through mechanisms involving apoptotic pathways. Further studies are needed to clarify its role and to evaluate its potential clinical relevance.
Full text 8,369 characters · extracted from oa-doi-fallback · 2 sections · click to expand

Abstract

Buserelin, a gonadotropin-releasing hormone agonist, reduces gonadotropin and estrogen levels and is commonly used to alleviate the symptoms of endometriosis. Vitamin D3 has been reported to exhibit anti-inflammatory and pro-apoptotic properties, which may contribute to the regression of endometrial lesions. We aimed to investigate the effects of vitamin D3 on the regression and recurrence prevention of endometrial implant sites through the induction of apoptosis comparable to buserelin acetate in an experimental rat endometriosis model. Endometrial implant size and adhesion scores were evaluated following treatment. Microscopic analyses were performed using hematoxylin–eosin-stained preparations. Apoptotic activity was assessed by TUNEL assay, along with the expression of Bcl-2 and Bax antibodies. Untreated rats exhibited larger implant volumes, severe glandular and stromal alterations, and pronounced inflammatory infiltration. In contrast, vitamin D3 and buserelin treatments reduced implant size and adhesion scores. The vitamin D3–treated group demonstrated a high density of TUNEL-positive cells. Increased expression of Bcl-2 protein was found in untreated groups whereas, increased expression of Bax protein was found in both treated groups. In conclusion, vitamin D₃ may have contributed to the regression of endometrial implants, possibly through mechanisms involving apoptotic pathways. Further studies are needed to clarify its role and to evaluate its potential clinical relevance. Similar content being viewed by others Data availability No datasets were generated or analysed during the current study. Change history 08 June 2026 Funding and acknowledgment was added

References

Abbas MA, Taha MO, Disi AM, Shomaf M (2013) Regression of endometrial implants treated with vitamin D3 in a rat model of endometriosis. Eur J Pharmacol 715(1–3):72–75. https://doi.org/10.1016/j.ejphar.2013.06.016 Adilbayeva A, Kunz J (2024) Pathogenesis of endometriosis and endometriosis-associated cancers. Int J Mol Sci 25(14):7624. https://doi.org/10.3390/ijms25147624 Ali M, Raslan M, Ciebiera M, Zaręba K, Al-Hendy A (2022) Current approaches to overcome the side effects of GnRH analogs in the treatment of patients with uterine fibroids. Expert Opin Drug Saf 21(4):477–486. https://doi.org/10.1080/14740338.2022.1989409 Blauer KL, Collins RL (1988) The effect of intraperitoneal progesterone on postoperative adhesion formation in rabbits. Fertil Steril 49(1):144–149 Brust LA, Linxweiler M, Schnatmann J, Kühn JP, Knebel M, Braun et al (2024) Effects of vitamin D on tumor cell proliferation and migration, tumor initiation and anti-tumor immune response in head and neck squamous cell carcinomas. Biomed Pharmacother 180:117497. https://doi.org/10.1016/j.biopha.2024.117497 Chauhan JK, Dubey PK, Rai S, Tripathi A (2024) Induction and characterization of a rat model of endometriosis. Sci Rep 14(1):18827. https://doi.org/10.1038/s41598-024-69440-1 Chen S, Liu Y, Zhong Z, Wei C, Liu Y, Zhu X (2023) Peritoneal immune microenvironment of endometriosis: role and therapeutic perspectives. Front Immunol 14:1134663. https://doi.org/10.3389/fimmu.2023.1134663 Dallavalasa S, Tulimilli SV, Bettada VG, Karnik M, Uthaiah CA, Anantharaju PG et al (2024) Vitamin D in cancer prevention and treatment: a review of epidemiological, preclinical, and cellular studies. Cancers (Basel) 16(18):3211. https://doi.org/10.3390/cancers16183211 Darzynkiewicz Z, Galkowski D, Zhao H (2008) Analysis of apoptosis by cytometry using TUNEL assay. Methods (San Diego Calif) 44(3):250–4. https://doi.org/10.1016/j.ymeth.2007.11.008 Dong J, Ling Wong S, Wai Lau C, Liu J, Wang YX, Dan He Z et al (2013) Calcitriol restores renovascular function in estrogen-deficient rats through downregulation of cyclooxygenase-2 and the thromboxane-prostanoid receptor. Kidney Int 84(1):54–63. https://doi.org/10.1038/ki.2013.12 Furman BL (2017) Buserelin. xPharm 2007(1–5). https://doi.org/10.1016/B978-008055232-3.61354-6 Hickey M, Ballard K, Farquhar C (2014) Endometr BMJ 19:348. https://doi.org/10.1136/bmj.g1752 Lessey BA (2000) Medical management of endometriosis and infertility. Fertil Steril 73(6):1089–1096. https://doi.org/10.1016/S0015-0282(00)00519-7 Mariani M, Viganò P, Gentilini D, Camisa B, Caporizzo E, Di Lucia P et al (2012) The selective vitamin D receptor agonist, elocalcitol, reduces endometriosis development in a mouse model by inhibiting peritoneal inflammation. Hum Reprod 27(7):2010–2019. https://doi.org/10.1093/humrep/des150 Meresman GF, Vighi S, Buquet RA, Contreras-Ortiz O, Tesone M, Rumi L (2000) Apoptosis and expression of Bcl-2 and Bax in eutopic endometrium from women with endometriosis. Fertil Steril 74(4):760–766. https://doi.org/10.1016/S0015-0282(00)01522-3 Ou Y, Wang H, Zhou C, Chen Y, Lyu J, Feng M, Huang X (2025) Endometriosis-associated infertility: multi-omics insights into pathogenesis and precision therapeutics. Front Endocrinol 16:1613334. https://doi.org/10.3389/fendo.2025.1613334 Özel Ş, Süntar İ, Gökay NE, Türkmenoğlu TT, Demirel MA (2020) The effectiveness of Teucrium chamaedrys L. extracts on endometriotic implant regression in rat endometriosis model. Vet Res Forum 11(4):305–309. https://doi.org/10.30466/vrf.2019.105229.2500 Piriyev E, Schiermeier S, Römer T (2025) Hormonal treatment of endometriosis: A narrative review. Pharmaceuticals 18(4):588. https://doi.org/10.3390/ph18040588 Stratton P, Winkel CA, Sinaii N, Merino MJ, Zimmer C, Nieman LK (2002) Location, color, size, depth, and volume may predict endometriosis in lesions resected at surgery. Fertil Steril 78(4):743–749. https://doi.org/10.1016/S0015-0282(02)03337-X Veeresh PKM, Basavaraju CG, Dallavalasa S, Anantharaju PG, Natraj SM, Sukocheva OA, Madhunapantula SV (2023) Vitamin D3 inhibits the viability of breast cancer cells in vitro and Ehrlich ascites carcinomas in mice by promoting apoptosis and cell cycle arrest and by impeding tumor angiogenesis. Cancers. https://doi.org/10.3390/cancers15194833 Vercellini P, Buffo C, Viganò P, Somigliana E (2025) Update on medical treatment of endometriosis: new drugs or new therapeutic approaches? Gynecol Obstet Investig 90(6):535–559. https://doi.org/10.1159/000542947 Vernon MW, Wilson EA (1985) Studies on the surgical induction of endometriosis in the rat. Fertil Steril 44(5):684–694. https://doi.org/10.1016/S0015-0282(16)48988-0 Xie B, Liao M, Huang Y, Hang F, Ma N, Hu Q et al (2024) Association between vitamin D and endometriosis among American women: National health and nutrition examination survey. PLoS One 19(1):e0296190. https://doi.org/10.1371/journal.pone.0296190 Zhang H, Sheng S, Pan Z, Zhao L, Yang C, Li C, Wang F (2023) Immune and endocrine regulation in endometriosis: what we know. JEUD 4:100049. https://doi.org/10.1016/j.jeud.2023.100049 Acknowledgment This study was funded by the Gazi University Scientific Research Projects Unit under project code 01/2019-53. Funding Our research was financially supported by the Gazi University Scientific Research Projects Unit. Author information Authors and Affiliations Contributions Supervision, conception and study design; SÖ, MAD and TP. Writing original draft; AK, SÖD, MAD and ZY. Methodology; MAD, SÖ, AK and SÖD. Figure construction; SÖ, ZY and AK. Review and editing of draft; all. Authors read and approved the final manuscript. Corresponding author Ethics declarations Conflict of interest The authors declare no Conflict of interest. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Köylü, A., Ömeroğlu, S., Dizakar, S.Ö.A. et al. Vitamin D3 promotes regression of endometrial implants comparable to buserelin in a rat model of endometriosis. J Mol Histol 57, 216 (2026). https://doi.org/10.1007/s10735-026-10879-z Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s10735-026-10879-z

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

MeSH descriptors

Buserelin Buserelin Buserelin Buserelin Buserelin Buserelin Buserelin Buserelin Buserelin Buserelin Buserelin Buserelin Buserelin Buserelin Buserelin Buserelin Buserelin Buserelin Buserelin Buserelin

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (24)

Source provenance

europepmc
last seen: 2026-08-04T06:16:37.499272+00:00
openalex
last seen: 2026-08-04T06:09:38.241991+00:00
pubmed
last seen: 2026-08-04T06:11:27.203953+00:00
License: public-domain-us · commercial use OK · attribution required
Courtesy of the U.S. National Library of Medicine