Evidence map›Paper›PMID 34647523›Full record

ArticleThe Journal of endocrinology2021

Effects of PD-1 blockade on ovarian follicles in a prepubertal female mouse.

Pauline C Xu, Yi Luan, Seok-Yeong Yu, Jing Xu, Donald W Coulter, So-Youn Kim

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of endocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
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

21 citing papers in PubMed, 27 citations in OpenAlex.

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  11. Immune Checkpoint Inhibitors Impact Fertility: A Review.Reviews on recent clinical trials · 2025
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  19. Expression and T cell regulatory action of the PD-1 immune checkpoint in the ovary and fallopian tube.American journal of reproductive immunology (New York, N.Y. : 1989) · 2023
    Article
  20. Article
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

6 authors at 2 institutions in 1 country.

Pauline C XuOlson Center for Women's Health, Department of Obstetrics and Gynecology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska.
Yi LuanOlson Center for Women's Health, Department of Obstetrics and Gynecology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska.
Seok-Yeong YuOlson Center for Women's Health, Department of Obstetrics and Gynecology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska.
Jing XuDivision of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon.
Donald W CoulterDivision of Pediatric Hematology/Oncology, Department of Pediatrics, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska.
So-Youn KimOlson Center for Women's Health, Department of Obstetrics and Gynecology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska.
University of Nebraska Medical Center · USOregon National Primate Research Center · US

Funding

Development of mechanism-based ovarian reserve protecting adjuvant therapies against gonadotoxic therapeutic agentsR01HD096042 · NICHD · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI KIM, SO-YOUN · 2019 to 2023
$1.6M
NICHD NIH HHS R01 HD096042
6 · The paper itself

Abstract

Immunotherapy has emerged at the forefront of cancer treatment. Checkpoint inhibitor pembrolizumab (KEYTRUDA), a chimeric antibody which targets programmed cell death protein 1 (PD-1), has been approved by the Food and Drug Administration (FDA) for use in pediatric patients with relapsed or refractory classical Hodgkin's lymphoma. However, there is currently no published data regarding the effects of pembrolizumab on the ovary of female pediatric patients. In this study, prepubertal immunocompetent and immunodeficient female mice were injected with pembrolizumab or anti-mouse PD-1 antibody. The number of primordial follicles significantly decreased post-injection of both pembrolizumab and anti-mouse PD-1 antibody in immunocompetent mice. However, no changes in follicle numbers were observed in immunodeficient nude mice. Superovulation test and vaginal opening experiments suggest that there is no difference in the number of cumulus-oocyte complexes (COCs) and the timing of puberty onset between the control and anti-mouse PD-1 antibody treatment groups, indicating that there is no effect on short-term fertility. Elevation of pro-inflammatory cytokine TNF-α following COX-2 upregulation was observed in the ovary. CD3+ T-cell infiltration was detected within some ovarian follicles and between stromal cells of the ovaries in mice following treatment with anti-mouse PD-1 antibody. Thus, PD-1 immune checkpoint blockade affects the ovarian reserve through a mechanism possibly involving inflammation following CD3+ T-cell infiltration.

Indexed as

AnimalsAnimals, NewbornAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalCell CountFemaleImmune Checkpoint InhibitorsInfertility, FemaleMiceMice, NudeOocytesOvarian FollicleOvarian ReserveOvaryProgrammed Cell Death 1 ReceptorSexual MaturationAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalImmune Checkpoint InhibitorspembrolizumabProgrammed Cell Death 1 Receptorgonadotoxicityimmune checkpoint inhibitorsimmunotherapyoncofertilityovarian reserve

Identifiers

PMID34647523
PMCPMC8630981
OpenAlexW3206342476

What OpenQuestion holds

Textmetadata
LicenceTDM
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.