RESUMO
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). CONCLUSION: These challenging results provide insight in understanding the pathophysiology of endometriosis and evoke a correlation between lesion architecture and symptomatology.
