title: Pregnancy affects morphology of induced endometriotic lesions in a mouse model through alteration of proliferation and angiogenesis.
abstract: OBJECTIVE
  Pregnancy is known to alleviate the symptoms of endometriosis and is also known to be a pro-angiogenic condition affecting blood and lymphatic vessels. However, angiogenesis actively participates in the development of endometriosis. The objective of our study was to study the impact of pregnancy on endometriotic tissue. Study design We performed a cross-sectional, control versus treatment study in a mouse model of endometriosis. Thirty-one female C57Bl6 mice were mated and became pregnant and 31 females were not mated and served as control. Intraperitoneal endometriotic lesions were surgically induced in C57Bl6 mice which were subsequently mated or not (group P: pregnant, group NP: non-pregnant). P and NP mice were sacrificed on day E15.5 of the pregnancy of P mice and lesions were harvested. Lesions were weighed and analyzed by histology, immunohistology, flow cytometry and real-time quantitative RT-PCR (qRT-PCR).
  
  
  RESULTS
  Pregnancy reduced lesion weight, decreased the proportion of cystic component (0.02 vs. 0.4; p<0.001) and modified the architecture of peritoneal endometriotic lesions. Pregnancy also increased cell proliferation in both stromal and glandular tissue as shown by the increase in Ki 67-positive cells in the P group (glandular: 19 vs. 3.9%, p<0.001; stromal: 8.7 vs. 3.3%, p<0.01). Finally, pregnancy increased angiogenesis in endometriotic lesions as indicated by an increased microvessel density (CD-31 and LYVE-1 stainings: respectively 2.2 vs. 5.1%, p<0.01 and 0.4 vs. 0.9%, p<0.001), an increased number of LYVE1 positive cells evaluated by flow cytometry (18.9 vs. 4.6%, p<0.05) and a rise in VEGF-A, -R2 and -R3 RNA expression shown by qRT-PCR (p<0.001; p<0.01; p<0.05).
  
  
  CONCLUSIONS
  These challenging results provide insight in understanding the pathophysiology of endometriosis and evoke a correlation between lesion architecture and symptomatology.
authors.affiliation: Inserm UMRS938, Université Pierre et Marie Curie, Paris, France; Service de Gynécologie-Obstétrique, Hôpital Tenon, Assistance Publique des Hôpitaux de Paris, Université Pierre et Marie Curie Paris 6, GRC 6-UPMC Centre Expert en Endométriose (C3E), France. Electronic address: drcohenjonathan@gmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Cohen
authors.affiliation: Inserm UMRS938, Université Pierre et Marie Curie, Paris, France; Service de Gynécologie-Obstétrique, Hôpital Tenon, Assistance Publique des Hôpitaux de Paris, Université Pierre et Marie Curie Paris 6, GRC 6-UPMC Centre Expert en Endométriose (C3E), France.
authors.forename: I
authors.initials: I
authors.lastname: Naoura
authors.affiliation: Inserm UMRS938, Université Pierre et Marie Curie, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Castela
authors.affiliation: Inserm UMRS938, Université Pierre et Marie Curie, Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Von N'Guyen
authors.affiliation: Inserm UMRS938, Université Pierre et Marie Curie, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Oster
authors.affiliation: Inserm UMRS938, Université Pierre et Marie Curie, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Fontaine
authors.affiliation: Inserm UMRS938, Université Pierre et Marie Curie, Paris, France; Service de Gynécologie-Obstétrique, Hôpital Tenon, Assistance Publique des Hôpitaux de Paris, Université Pierre et Marie Curie Paris 6, GRC 6-UPMC Centre Expert en Endométriose (C3E), France.
authors.forename: N
authors.initials: N
authors.lastname: Chabbert-Buffet
authors.affiliation: Inserm UMRS938, Université Pierre et Marie Curie, Paris, France; Service de Gynécologie-Obstétrique, Hôpital Tenon, Assistance Publique des Hôpitaux de Paris, Université Pierre et Marie Curie Paris 6, GRC 6-UPMC Centre Expert en Endométriose (C3E), France.
authors.forename: E
authors.initials: E
authors.lastname: Darai
authors.affiliation: Inserm UMRS938, Université Pierre et Marie Curie, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Aractingi
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology*; D003430:Cross-Sectional Studies; D004195:Disease Models, Animal; D004715:Endometriosis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D004717:Endometrium / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D042601:Lymphatic Vessels / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D012313:RNA / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D012313:RNA; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3
keywords: Angiogenesis; Cell proliferation; Endometriosis; Mouse model; Pregnancy