Evidence map›Paper›PMID 40611136›Full record

ArticleReproductive biology and endocrinology : RB&E2025

A dual-drug strategy to enhance the function of cryopreserved ovaries by promoting revascularization and inhibiting follicle over-activation.

Lingyu Li, Jian Yang, Longzhong Jia, Jing Liang, Kaixin Cheng, Xuebing Yang, Lu Mu, Ge Wang, Kaiying Geng, Qiuxian Hu and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Reproductive biology and endocrinology : RB&E, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Lingyu Li *State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Jian Yang *State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Longzhong JiaState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Jing LiangState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Kaixin ChengState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Xuebing YangState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Lu MuState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Ge WangState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Kaiying GengState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Qiuxian HuState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Xueqiang XuState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Zhen LiState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Guoliang XiaState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Ting GuoInstitute of Women, Children, and Reproductive Health, Shandong University, Ji'nan, Shandong, 250012, China.
Jiawei ZhangCollege of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, China. cbsjiaweizhang@163.com.
Yan ZhangState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China. yanzhang1011@cau.edu.cn.
Hua ZhangState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China. huazhang@cau.edu.cn.

Funding

Chinese Universities Scientific Fund to H.Z. 2024TC017Innovative Project of State Key Laboratory of Animal Biotech Breeding to H.Z. 2023SKLAB1-6Key Program of National Natural Science Foundation of China to H.Z. 82230051National Key Research and Development Program of China 2022YFC2703000National Key Research and Development Program of China 2024YFC2706600National Natural Science Foundation of China 82371664National Natural Science Foundation of China to J.Z. 32200704
6 · The paper itself

Abstract

backgroundOvarian tissue cryopreservation and transplantation (OTCT) is a promising approach for fertility preservation. However, significant follicle loss after transplantation challenges long-term reproductive recovery. Although primordial follicle loss and ischemic damage are known contributors, the underlying mechanisms and effective strategies to mitigate these damages are still lacking.

methodsOvarian tissues from wild-type or Tek-CreER

resultsOur study observed a rapid decline in follicle numbers shortly after transplantation in a mouse model. Proteomic analysis and high-resolution 3D imaging revealed that this depletion was primarily due to damage to tip cells, which are crucial for angiogenesis, and the overactivation of dormant primordial follicles. Damage to tip cells compromised vascular reconstruction, leading to ischemic injury, while mechanical handling during tissue isolation and cryopreservation triggered excessive follicle activation. We implemented a combination therapy using rapamycin to inhibit follicle activation and VEGFA to promote angiogenesis prior to transplantation. This approach significantly improved follicle survival, extended reproductive function, and enhanced oocyte quality.

conclusionOur study provides a practical strategy for preserving the reproductive potential of cryopreserved ovarian tissues by simultaneously targeting vascular integrity and follicle stability through the dual drug strategy of VEGFA and rapamycin combine treatment.

Indexed as

CryopreservationFertility PreservationNeovascularization, PhysiologicOvarian FollicleOvarySirolimusAnimalsFemaleMiceVascular Endothelial Growth Factor ASirolimusVascular Endothelial Growth Factor A3D high resolution imagingLong-term fertility preservationOvarian cryopreservationPrimordial follicle activationTip cell

Identifiers

PMID40611136
PMCPMC12224590

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.