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Reprod Biol Endocrinol. 2017 Mar 9;15(1):18. doi: 10.1186/s12958-017-0235-8.

Mesenchymal stem cell-derived angiogenin promotes primodial follicle survival and angiogenesis in transplanted human ovarian tissue.

Zhang Y1,2,3, Xia X1,4, Yan J1,2,3, Yan L1,2,3, Lu C1,2,3, Zhu X1,2,3, Wang T1,2,5, Yin T1,2,3, Li R1,2,3, Chang HM6, Qiao J7,8,9.

Author information

1
Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, No.49 North HuaYuan Road, HaiDian District, Beijing, 100191, China.
2
Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, 100191, China.
3
Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China.
4
Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Shenzhen Hospital, No.1120 Lotus Road, FuTian District, Shenzhen, Guangdong, 518000, China.
5
Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, 100004, China.
6
Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, V5Z4H4, Canada.
7
Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, No.49 North HuaYuan Road, HaiDian District, Beijing, 100191, China. jie.qiao@263.net.
8
Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, 100191, China. jie.qiao@263.net.
9
Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China. jie.qiao@263.net.

Abstract

BACKGROUND:

We have recently reported that human bone marrow-derived mesenchymal stem cells (MSCs) facilitate angiogenesis and prevent follicle loss in xenografted human ovarian tissues. However, the mechanism underlying this effect remains to be elucidated. Thus, determining the paracrine profiles and identifying the key secreted factors in MSCs co-transplanted with ovarian grafts are essential for the future application of MSCs.

METHODS:

In this study, we used cytokine microarrays to identify differentially expressed proteins associated with angiogenesis in frozen-thawed ovarian tissues co-transplanted with MSCs. The function of specific secreted factors in MSCs co-transplanted with human ovarian tissues was studied via targeted blockade with short-hairpin RNAi and the use of monoclonal neutralizing antibodies.

RESULTS:

Our results showed that angiogenin (ANG) was one of the most robustly up-regulated proteins (among 42 protein we screened, 37 proteins were up-regulated). Notably, the targeted depletion of ANG with short-hairpin RNAi (shANG) or the addition of anti-ANG monoclonal neutralizing antibodies (ANG Ab) significantly reversed the MSC-stimulated angiogenesis, increased follicle numbers and protective effect on follicle apoptosis.

CONCLUSION:

Our results indicate that ANG plays a critical role in regulating angiogenesis and follicle survival in xenografted human ovarian tissues. Our findings provide important insights into the molecular mechanism by which MSCs promote angiogenesis and follicle survival in transplanted ovarian tissues, thus providing a theoretical basis for their further application.

KEYWORDS:

Angiogenin; Fertility preservation; Follicle survival; Mesenchymal stem cell; Ovarian tissue transplantation

PMID:
28274269
PMCID:
PMC5343383
DOI:
10.1186/s12958-017-0235-8
[Indexed for MEDLINE]
Free PMC Article

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