Interplay between Endometriosis and Pregnancy in a Mouse Model.
OBJECTIVE
To evaluate the effect of endometriosis on fertility and the levels of the IL-2 and IFN-γ in the peritoneal fluid in a mouse model; to evaluate the effect of pregnancy on endometriotic lesion growth, apoptosis and cell proliferation.


METHODS
Two month old C57BL/6 female mice underwent either a surgical procedure to induce endometriosis or a sham surgery. Four weeks after surgery mice were mated and sacrificed at day 18 of pregnancy. Number of implantation sites, fetuses and fetal weight were recorded. Endometriotic lesions were counted, measured, excised and fixed. Apoptosis and cell proliferation were evaluated in lesions by TUNEL and immunohistochemistry for PCNA respectively. Levels of IL-2 and IFN-γ were assessed by ELISA in the peritoneal fluid.


RESULTS
Pregnancy rate (i.e. pregnant mice/N) decreased in mice with endometriosis. However there were no significant differences in resorption rate, litter size and pup weight between groups. IFN-γ augmented in endometriosis mice independently of pregnancy outcome. Additionally IFN-γ increased in pregnant endometriosis mice compared to pregnant sham animals. While IFN-γ increased in non pregnant versus pregnant mice in the sham group, IL-2 was increased in non pregnant mice in the endometriosis group. The size of endometriotic lesions increased in pregnant mice while apoptosis increased in the stroma and cell proliferation decreased in the epithelium of these lesions. Additionally, leukocyte infiltration, necrosis and decidualization were increased in the same lesions.


CONCLUSIONS
Pregnancy rate is reduced in this mouse model of endometriosis. Levels of IL-2 are increased in the peritoneal fluid of mice with endometriosis suggesting a role of this cytokine in infertility related to this disease. The size of endometriotic lesions is increased in pregnant mice; however pregnancy has a beneficial effect on lesions by decreasing cell proliferation and by increasing apoptosis, decidualization and necrosis.
Instituto de Biología y Medicina Experimental (IBYME)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Mariela Andrea
MA
Bilotas
Instituto de Biología y Medicina Experimental (IBYME)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Carla Noemí
CN
Olivares
Instituto de Biología y Medicina Experimental (IBYME)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Analía Gabriela
AG
Ricci
Instituto de Biología y Medicina Experimental (IBYME)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Juan Ignacio
JI
Baston
Instituto de Biología y Medicina Experimental (IBYME)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Tatiana Soledad
TS
Bengochea
Instituto de Biología y Medicina Experimental (IBYME)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Gabriela Fabiana
GF
Meresman
Instituto de Biología y Medicina Experimental (IBYME)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Rosa Inés
RI
Barañao
D000818:Animals; D001202:Ascitic Fluid / Q000378:metabolism; D004715:Endometriosis / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D005260:Female; D007247:Infertility, Female / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
D007376:Interleukin-2; D007371:Interferon-gamma