Optimization of Endometrial Decidualization in the Menstruating Mouse Model for Preclinical Endometriosis Research

article OA: closed CC0 ⤵ 11 in-corpus citations
AI-generated summary by claude@2026-06+body, 2026-06-12

Laparoscopic and laparotomic intrauterine oil injections yielded higher endometrial decidualization than sham injections, though full decidualization requires further optimization.

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

AI-generated deep summary by claude@2026-06, 2026-06-12 · read from full text

The study investigated how to induce endometrial decidualization most effectively in ovariectomized C57BL/6J mice using estrogen and progesterone, comparing intrauterine oil delivery via laparotomy, laparoscopy, or the nontraumatic vagina. After hormones and oil infusion (20 µL per horn), decidualization was assessed 4 days later by macroscopic and microscopic examination (H&E and desmin), along with uterine weight and hormone levels; pellet removal and hysterectomy after a defined interval preceded tissue collection. Laparoscopic and laparotomic oil injection yielded higher proportions of macroscopic bicornuate decidualization than sham, and laparotomy produced significantly higher bicornuate decidualization than vaginal injection; however, relative desmin-positive endometrial surface area was not broadly different across all comparisons, and full bicornuate decidualization was not consistently achieved. This paper is centrally about endometriosis — it specifically optimizes the menstruating mouse model by maximizing endometrial decidualization for preclinical endometriosis research.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

BackgroundTo induce endometrial decidualization in rodents, an intrauterine oil stimulus can be delivered via the nontraumatic vagina or via the traumatic laparotomy. However, there is considerable variation in amount of decidualization using these inducing methods. Therefore, we studied which oil delivery route could achieve the highest rate of endometrial decidualization along the full length of both uterine horns.MethodsTo induce decidualization, ovariectomized C57Bl/6J mice were injected with estrogen (100 ng/day; 3 days). A progesterone pellet (5 mg) was implanted subcutaneously, followed by estrogen injections (5 ng/day; 3 days). Oil (20 µL/horn) was injected in the uterus via laparotomy, laparoscopy, or vagina. Four days later, the pellet was removed, followed by hysterectomy after 4 to 6 hours. Endometrial decidualization was evaluated macroscopically and microscopically using hematoxylin and eosin and desmin staining. Furthermore, uterine weight and hormone levels were measured.ResultsThe proportion of animals with macroscopic bicornuate decidualization was higher after laparoscopic (83%) and laparotomic (89%) injection than after sham injection (11%). Furthermore, macroscopic bicornuate decidualization was significantly higher after laparotomic injection (89%) compared to the vaginal injection (38%). Uterine weight and endometrial surface area were significantly higher in both laparotomy and laparoscopy groups compared to the sham group, while the relative desmin-positive endometrial surface area was only significantly different between the laparotomy and the sham animals.ConclusionMethods using laparoscopic and laparotomic intrauterine oil injection resulted in a higher amount of decidualized endometrium compared to sham injection, although further optimization is needed to reach full bicornuate decidualization.
Full text 10,714 characters · extracted from oa-doi-fallback · 2 sections · click to expand

Abstract

Background: To induce endometrial decidualization in rodents, an intrauterine oil stimulus can be delivered via the nontraumatic vagina or via the traumatic laparotomy. However, there is considerable variation in amount of decidualization using these inducing methods. Therefore, we studied which oil delivery route could achieve the highest rate of endometrial decidualization along the full length of both uterine horns. Methods: To induce decidualization, ovariectomized C57BI/6J mice were injected with estrogen (100 ng/day; 3 days). A progesterone pellet (5 mg) was implanted subcutaneously, followed by estrogen injections (5 ng/day; 3 days). Oil (20 μL/horn) was injected in the uterus via laparotomy, laparoscopy, or vagina. Four days later, the pellet was removed, followed by hysterectomy after 4 to 6 hours. Endometrial decidualization was evaluated macroscopically and microscopically using hematoxylin and eosin and desmin staining. Furthermore, uterine weight and hormone levels were measured. Results: The proportion of animals with macroscopic bicornuate decidualization was higher after laparoscopic (83%) and laparotomic (89%) injection than after sham injection (I 1%). Furthermore, macroscopic bicornuate decidualization was significantly higher after laparotomic injection (89%) compared to the vaginal injection (38%). Uterine weight and endometrial surface area were significantly higher in both laparotomy and laparoscopy groups compared to the sham group, while the relative desmin-positive endometrial surface area was only significantly different between the laparotomy and the sham animals. Conclusion: Methods using laparoscopic and laparotomic intrauterine oil injection resulted in a higher amount of decidualized endometrium compared to sham injection, although further optimization is needed to reach full bicornuate decidualization. Similar content being viewed by others

References

Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447): 1789–1799. Wheeler JM. Epidemiology of endometriosis-associated infertility. J Reprod Med. 1989;34(1): 41–46. Stilley JA, Birt JA, Sharpe-Timms KL. Cellular and molecular basis for endometriosis-associated infertility. Cell Tissue Res. 2012;349(3):849–862. Sampson JA. Peritoneal endometriosis due to the menstrual dis-semination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol. 1927;14(4):422–469. Halme J, Hammond MG, Hulka JF, Raj SG, Talbert LM. Retro-grade menstruation in healthy women and in patients with endo-metriosis. Obstet Gynecol. 1984;64(2):151–154. O DF, Roskams T, Van den Eynde K, et al. The presence of endometrial cells in peritoneal fluid of women with and without endometriosis. Reprod Sci. 2017;24(2):242–251. Pullen N, Birch CL, Douglas GJ, Hussain Q, Pruimboom-Brees I, Walley RJ. The translational challenge in the development of new and effective therapies for endometriosis: a review of confidence from published preclinical efficacy studies. Hum Reprod Update. 2011;17(6):791–802. Tirado-Gonzalez I, Barrientos G, Tariverdian N, et al. Endome-triosis research: animal models for the study of a complex disease. J Reprod Immunol. 2010;6(2):141–141. Grummer R. Animal models in endometriosis research. Hum Reprod Update. 2006;12(5):641–649. Peterse DP, Fassbender A, DF O, et al. Laparoscopic surgery: a new technique to induce endometriosis in a mouse model. Reprod Sci. 2016;23(10):1332–1339. Cheng CW, Licence D, Cook E, et al. Activation of mutated K-ras in donor endometrial epithelium and stroma promotes lesion growth in an intact immunocompetent murine model of endome-triosis. J Pathol. 2011;224(2):261–269. Greaves E, Cousins FL, Murray A, et al. A novel mouse model of endometriosis mimics human phenotype and reveals insights into the inflammatory contribution of shed endometrium. Am J Pathol. 2014;184(7):1930–1939. Bergqvist A, Jeppsson S, Kullander S, Ljungberg O. Human uter-ine endometrium and endometriotic tissue transplanted into nude mice. Morphologic effects of various steroid hormones. Am J Pathol. 1985;121(2):337–341. Bruner-Tran KL, Eisenberg E, Yeaman GR, Anderson TA, McBean J, Osteen KG. Steroid and cytokine regulation of matrix metalloproteinase expression in endometriosis and the establish-ment of experimental endometriosis in nude mice. J Clin Endo-crinol Metab. 2002;87(10):4782–4791. Rudolph M, Docke WD, Muller A, et al. Induction of overt men-struation in intact mice. PLoS One. 2012;7(3):e32922. Gellersen B, Brosens IA, Brosens JJ. Decidualization of the human endometrium: mechanisms, functions, and clinical per-spectives. Semin Reprod Med. 2007;25(6):445–453. Gellersen B, Brosens J. Cyclic AMP and progesterone receptor cross-talk in human endometrium: a decidualizing affair. J Endocrinol. 2003;178(3):357–372. Jabbour HN, Kelly RW, Fraser HM, Critchley HO. Endocrine regulation of menstruation. Endocr Rev. 2006;27(1): 17–46. Salamonsen LA. Tissue injury and repair in the female human reproductive tract. Reproduction. 2003;125(3):301–311. Finn CA, Pope M. Vascular and cellular changes in the decidua-lized endometrium of the ovariectomized mouse following cessation of hormone treatment: a possible model for menstruation. J Endocrinol. 1984;100(3):295–300. Brasted M, White CA, Kennedy TG, Salamonsen LA. Mimicking the events of menstruation in the murine uterus. Biol Reprod. 2003;69(4):1273–1280. Cousins FL, Murray A, Esnal A, Gibson DA, Critchley HO, Saunders PT. Evidence from a mouse model that epithelial cell migration and mesenchymal-epithelial transition contribute to rapid restoration of uterine tissue integrity during menstruation. PLoS One. 2014;9(1): e86378. Menning A, Walter A, Rudolph M, Gashaw I, Fritzemeier KH, Roese L. Granulocytes and vascularization regulate uterine bleed-ing and tissue remodeling in a mouse menstruation model. PLoS One. 2012;7(8):e41800. Xu XB, He B, Wang JD. Menstrual-like changes in mice are provoked through the pharmacologic withdrawal of progesterone using mifepristone following induction of decidualization. Hum Reprod. 2007;22(12):3184–3191. Kaitu’u-Lino TJ, Morison NB, Salamonsen LA. Estrogen is not essential for full endometrial restoration after breakdown: lessons from a mouse model. Endocrinology. 2007;148(10):5105–5111. Kaitu’u-Lino TJ, Ye L, Salamonsen LA, Girling JE, Gargett CE. Identification of label-retaining perivascular cells in a mouse model of endometrial decidualization, breakdown, and repair. Biol Reprod. 2012;86(6):184. Morison NB, Kaitu’u-Lino TJ, Fraser IS, Salamonsen LA. Stimulation of epithelial repair is a likely mechanism for the action of mifepristone in reducing duration of bleeding in users of progestogen-only contraceptives. Reproduction. 2008;136(2): 267–274. Morison NB, Zhang J, Kaitu’u-Lino TJ, Fraser IS, Salamonsen LA. The long-term actions of etonogestrel and levonorgestrel on decidualized and non-decidualized endometrium in a mouse model mimic some effects of progestogen-only contraceptives in women. Reproduction. 2007;133(1):309–321. Wang Q, Xu X, He B, Li Y, Chen X, Wang J. A critical period of progesterone withdrawal precedes endometrial breakdown and shedding in mouse menstrual-like model. Hum Reprod. 2013; 28(6): 1670–1678. Chen X, Liu J, He B, et al. Vascular endothelial growth factor (VEGF) regulation by hypoxia inducible factor-1 alpha (HIF1A) starts and peaks during endometrial breakdown, not repair, in a mouse menstrual-like model. Hum Reprod. 2015;30(9): 2160–2170. Milligan SR, Cohen PE. Silastic implants for delivering physio-logical concentrations of progesterone to mice. Reprod Fertil Dev. 1994;6(2):235–239. Molinas CR, Mynbaev O, Pauwels A, Novak P, Koninckx PR. Peritoneal mesothelial hypoxia during pneumoperitoneum is a cofactor in adhesion formation in a laparoscopic mouse model. Fertil Steril. 2001;76(3):560–567. Reel JR, Lamb IJ, Neal BH. Survey and assessment of mamma-lian estrogen biological assays for hazard characterization. Fundam Appl Toxicol. 1996;34(2):288–305. Caligioni CS. Assessing reproductive status/stages in mice. Curr Protoc Neurosci. 2009; Appendix 4:Appendix 41. Goldman JM, Murr AS, Cooper RL. The rodent estrous cycle: characterization of vaginal cytology and its utility in toxicological studies. Birth Defects Res B Dev Reprod Toxicol. 2007;80(2): 84–97. Glasser SR, Julian J. Intermediate filament protein as a marker of uterine stromal cell decidualization. Biol Reprod. 1986;35(2): 463–474. Pera M, Nelson H, Rajkumar SV, Young-Fadok TM, Burgart LJ. Influence of postoperative acute-phase response on angiogenesis and tumor growth: open vs. laparoscopic-assisted surgery in mice. J Gastrointest Surg. 2003;7(6):783–790. Ferrero H, Buigues A, Martinez J, Simon C, Pellicer A, Gomez R. A novel homologous model for noninvasive monitoring of endometriosis progression. Biol Reprod. 2017;96(2): 302–312. Buxton LE, Murdoch RN. Lectins, calcium ionophore A23187 and peanut oil as deciduogenic agents in the uterus of pseudopregnant mice: effects of tranylcypromine, indo-methacin, iproniazid and propranolol. Aust J Biol Sci. 1982;35(1): 63–72. Herington JL, Underwood T, McConaha M, Bany BM. Paracrine signals from the mouse conceptus are not required for the normal progression of decidualization. Endocrinology. 2009;150(9): 4404–4413. Edwards C, Milligan SR. Uterine blood flow during the develop-ment and regression of the decidual cell reaction in ovariecto-mized, steroid-treated mice. J Reprod Fertil. 1987;81(2):525–532. Oliveira SF, Greca CP, Abrahamsohn PA, Reis MG, Zorn TM. Organization of desmin-containing intermediate filaments during differentiation of mouse decidual cells. Histochem Cell Biol. 2000;113(4):319–327. Corona R, Verguts J, Binda MM, Molinas CR, Schonman R, Koninckx PR. The impact of the learning curve on adhesion formation in a laparoscopic mouse model. Fertil Steril. 2011;96(1):193–197. Das SK. Cell cycle regulatory control for uterine stromal cell decidualization in implantation. Reproduction. 2009;137(6):889–899. Nair AR, Taylor HS. Amenorrhea. In: Santoro NF, Neal-Perry G, eds. A Case-Based, Clinical Guide, NY: Humana Press; 2010:XII 220. Ramathal CY, Bagchi IC, Taylor RN, Bagchi MK. Endometrial decidualization: of mice and men. Semin Reprod Med. 2010; 28(1): 17–26. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Peterse, D., Clercq, K.D., Goossens, C. et al. Optimization of Endometrial Decidualization in the Menstruating Mouse Model for Preclinical Endometriosis Research. Reprod. Sci. 25, 1577–1588 (2018). https://doi.org/10.1177/1933719118756744 Published: Version of record: Issue date: DOI: https://doi.org/10.1177/1933719118756744

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

Condition tags

endometriosis

MeSH descriptors

Decidua Endometriosis Menstruation Sesame Oil Animals Decidua Decidua Disease Models, Animal Endometriosis Estrogens Estrogens Estrogens Female Laparoscopy Laparotomy Mice, Inbred C57BL Progesterone Progesterone Progesterone Sesame Oil

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 (45)

Cited by (11)

Source provenance

europepmc
last seen: 2026-08-11T06:11:44.160905+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-05-13T22:19:55.107525+00:00
unpaywall
last seen: 2026-08-11T06:58:28.661508+00:00
License: CC0 · commercial use OK