Platelets are an unindicted culprit in the development of endometriosis: clinical and experimental evidence.
OBJECTIVE
Do platelets play any role in the development of endometriosis?


CONCLUSIONS
Activated platelets aggregate in endometriotic lesions and play important roles in the development of endometriosis.


BACKGROUND
Platelets play important roles in cancer development and metastasis but there is no published study on their role in the development of endometriosis, even though endometriotic lesions undergo repeated cycles of tissue injury and repair, which characteristically involve platelets.


METHODS
Cross-sectional clinical studies of women with and without endometriosis, in vitro experimentation, and animal studies using platelet and/or macrophage depletion.


METHODS
Immunohistochemistry analysis of ectopic/eutopic endometrial tissues from 58 women with and 47 without endometriosis. Proliferation assay, cell cycle analysis by flow cytometry, gene expression and protein analysis for COX-2, VEGF, MMP-9, and Bcl-2 using primary cell culture, and evaluation of the rate of platelet activation induced by peritoneal fluid from women with and without endometriosis. Two mouse experiments, one that evaluated the effect of platelet depletion on lesion development and its associated phenotypic changes, and the other, the effect of platelet and/or macrophage depletion.


RESULTS
We found that platelets aggregated in endometriotic lesions, concomitant with elevated VEGF expression and microvessel density. Co-culture of endometriotic stromal cells with platelets enhanced cellular proliferation, and increased the expression of COX-2, MMP-9, VEGF, and Bcl-2. IL-1β-induced COX-2 up-regulation and increased production of the coagulant TXA(2) in endometriotic stromal cells. Tissue factor (TF) expression was elevated in endometriosis and TF concentrations were significantly elevated both in the supernatant of cultured primary endometriotic stromal cells and in peritoneal fluid from women with endometriosis. Platelet depletion resulted in significantly reduced lesion size and improved hyperalgesia in mice with induced endometriosis.


CONCLUSIONS
This study is limited by its cross-sectional design and by its focus on ovarian endometriomas.


CONCLUSIONS
The demonstration that platelets are involved in the development of endometriosis provides a rationale for the use of anti-coagulants to treat endometriosis, and opens prospects for developing novel biomarkers for diagnostic or prognostic purposes.


BACKGROUND
Financial support for this study was provided by grants from the National Science Foundation of China, a grant from the Shanghai Science and Technology Commission, support from the Key Specialty Project of the Ministry of Health, People's Republic of China. None of the authors has any conflict of interest to disclose.
Shanghai OB/GYN Hospital, Fudan University, Shanghai 200011, China.
Ding
D
Ding
Shanghai OB/GYN Hospital, Fudan University, Shanghai 200011, China Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai, China.
Xishi
X
Liu
Shanghai OB/GYN Hospital, Fudan University, Shanghai 200011, China.
Jie
J
Duan
Shanghai OB/GYN Hospital, Fudan University, Shanghai 200011, China Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai, China hoxa10@outlook.com.
Sun-Wei
SW
Guo
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000328:Adult; D000818:Animals; D001792:Blood Platelets / Q000166:cytology*; D002453:Cell Cycle; D049109:Cell Proliferation; D003430:Cross-Sectional Studies; D004715:Endometriosis / Q000097:blood* / Q000503:physiopathology; D004717:Endometrium / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D064368:Healthy Volunteers; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010053:Ovary / Q000473:pathology; D015539:Platelet Activation; D010974:Platelet Aggregation; D011379:Prognosis; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism
D053583:Interleukin-1beta; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D013925:Thromboplastin; D013917:Thrombin
coagulation; endometriosis; macrophage; platelet; thrombin