PMID- 19095670 OWN - NLM STAT- MEDLINE DCOM- 20090825 LR - 20240316 IS - 1460-2350 (Electronic) IS - 0268-1161 (Print) IS - 0268-1161 (Linking) VI - 24 IP - 3 DP - 2009 Mar TI - Development of an animal experimental model to study the effects of levonorgestrel on the human endometrium. PG - 697-704 LID - 10.1093/humrep/den437 [doi] AB - BACKGROUND: This study was designed to develop an animal model to test the response of endometrium to local progestin delivery. METHODS: Proliferative human endometrium was subcutaneously grafted in two groups of SCID mice that received, 2 days before, a subcutaneous estradiol (E(2)) pellet and, for half of them, an additional implant of levonorgestrel (LNG). Mice were sacrificed 1, 2, 3 or 4 weeks after endometrial implantation and grafts were histologically analysed. Proliferation, steroid hormone receptors, blood vessels and stromal decidualization in both groups (E(2) and LNG) were immunohistologically evaluated and compared with proliferative endometrium and endometrium from women with an LNG intrauterine device. RESULTS: Grafts presented normal morphological endometrial characteristics. The expression of progesterone receptors was significantly decreased in glands and stroma of the LNG group as compared with the E(2) group at all times. A significant decrease was also observed in the stromal expression of estrogen receptor-alpha in the LNG group. At 4 weeks, the mean cross-sectional area of vessels was significantly higher after LNG treatment. CONCLUSIONS: These morphological and immunohistochemical characteristics are similar to those observed in women treated with local LNG. This mouse model might facilitate further investigations needed to understand the mechanisms responsible for the breakthrough bleeding frequently observed in progestin users. FAU - Alvarez Gonzalez, M-L AU - Alvarez Gonzalez ML AD - Laboratory of Tumor and Development Biology, GIGA-Research, B23, University de Liege, Sart-Tilman, B-4000 Liege, Belgium. FAU - Galant, C AU - Galant C FAU - Frankenne, F AU - Frankenne F FAU - Nisolle, M AU - Nisolle M FAU - Labied, S AU - Labied S FAU - Foidart, J-M AU - Foidart JM FAU - Marbaix, E AU - Marbaix E FAU - Beliard, A AU - Beliard A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20081217 PL - England TA - Hum Reprod JT - Human reproduction (Oxford, England) JID - 8701199 RN - 0 (Contraceptive Agents, Female) RN - 0 (Progestins) RN - 4TI98Z838E (Estradiol) RN - 5W7SIA7YZW (Levonorgestrel) SB - IM MH - Adult MH - Animals MH - Biopsy MH - Cell Proliferation MH - Contraceptive Agents, Female/administration & dosage/*pharmacology MH - Disease Models, Animal MH - Endometrium/*drug effects MH - Estradiol/administration & dosage MH - Female MH - Humans MH - Immunohistochemistry/methods MH - Levonorgestrel/administration & dosage/*pharmacology MH - Mice MH - Mice, SCID MH - Progestins/biosynthesis PMC - PMC2646790 EDAT- 2008/12/20 09:00 MHDA- 2009/08/26 09:00 PMCR- 2008/12/17 CRDT- 2008/12/20 09:00 PHST- 2008/12/20 09:00 [entrez] PHST- 2008/12/20 09:00 [pubmed] PHST- 2009/08/26 09:00 [medline] PHST- 2008/12/17 00:00 [pmc-release] AID - den437 [pii] AID - 10.1093/humrep/den437 [doi] PST - ppublish SO - Hum Reprod. 2009 Mar;24(3):697-704. doi: 10.1093/humrep/den437. Epub 2008 Dec 17.