Evidence map›Paper›PMID 34681817›Full record

ArticleInternational journal of molecular sciences2021

Granulocyte Colony-Stimulating Factor Restored Impaired Spermatogenesis and Fertility in an AML-Chemotherapy Mice Model.

Yulia Michailov, Ali AbuMadighem, Eitan Lunenfeld, Joseph Kapelushnik, Mahmoud Huleihel

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.6field-weighted citation impact, top 36% 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

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Ovarian stimulation by promoting basal follicular growth.Reproductive biology and endocrinology : RB&E · 2025
    Review
  5. Article
  6. Article
  7. Chemotherapy: how to reduce its adverse effects while maintaining the potency?Medical oncology (Northwood, London, England) · 2023
    Review
  8. 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

5 authors at 1 institution in 1 country.

Yulia MichailovThe Center of Advanced Research and Education in Reproduction (CARER), The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
Ali AbuMadighemThe Center of Advanced Research and Education in Reproduction (CARER), The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.ORCID 0000-0003-3436-0146
Eitan LunenfeldThe Center of Advanced Research and Education in Reproduction (CARER), Dep OB/GYN, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
Joseph KapelushnikSoroka Medical Center, Department of Pediatric Oncology and Hematology, Beer-Sheva, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
Mahmoud HuleihelThe Center of Advanced Research and Education in Reproduction (CARER), The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.ORCID 0000-0003-4246-9299
Ben-Gurion University of the Negev · IL

Funding

Israel Science Foundation 1418/19REPRODUCTION HUB, Faculty of Health Sciences 1111
6 · The paper itself

Abstract

Leukemia and treatment of male patients with anticancer therapy (aggressive chemotherapy and/or radiotherapy) may lead to infertility or even permanent male sterility. Their mechanisms of spermatogenesis impairment and the decrease in male fertility are not yet clear. We showed that under acute myeloid leukemia (AML) conditions, alone and in combination with cytarabine (CYT), there was significant damage in the histology of seminiferous tubules, a significant increase in apoptotic cells of the seminiferous tubules, and a reduction in spermatogonial cells (SALL and PLZF) and in meiotic (CREM) and post-meiotic (ACROSIN) cells. In addition, we showed a significant impairment in sperm parameters and fertilization rates and offspring compared to control. Our results showed a significant decrease in the expression of glial cell line-derived neurotrophic factor (GDNF), macrophage colony-stimulating factor (MCSF) and stem cell factor (SCF) under AML conditions, but not under cytarabine treatment compared to control. In addition, our results showed a significant increase in the pro-inflammatory cytokine interleukin-1 (IL-1) alpha in whole testis homogenates in all treatment groups compared to the control. Increase in IL-1 beta level was shown under AML conditions. We identified for the first time the expression of GCSF receptor (GCSFR) in sperm cells. We showed that GCSF injection in combination with AML and cytarabine (AML + CYT + GCSF) extended the survival of mice for a week (from 6.5 weeks to 7.5 weeks) compared to (AML + CYT). Injection of GCSF to all treated groups (post hoc), showed a significant impact on mice testis weight, improved testis histology, decreased apoptosis and increased expression of pre-meiotic, meiotic and post- meiotic markers, improved sperm parameters, fertility capacity and number of offspring compared to the controls (without GCSF). GCSF significantly improved the spermatogonial niche expressed by increased the expression levels of testicular GDNF, SCF and MCSF growth factors in AML-treated mice and (AML + CYT)-treated mice compared to those groups without GCSF. Furthermore, GCSF decreased the expression levels of the pro-inflammatory cytokine IL-12, but increased the expression of IL-10 in the interstitial compartment compared to the relevant groups without GCSF. Our results show for the first time the capacity of post injection of GCSF into AML- and CYT-treated mice to improve the cellular and biomolecular mechanisms that lead to improve/restore spermatogenesis and male fertility. Thus, post injection of GCSF may assist in the development of future therapeutic strategies to preserve/restore male fertility in cancer patients, specifically in AML patients under chemotherapy treatments.

Indexed as

AnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisCells, CulturedDisease Models, AnimalFertilityGranulocyte Colony-Stimulating FactorInfertility, MaleLeukemia, Myeloid, AcuteMaleMiceMice, Inbred C57BLSpermatogenesisSpermatogoniaTestisGranulocyte Colony-Stimulating Factoracute myeloid leukemia (AML)granulocyte-colony-stimulating factor (GCSF)male infertilitysperm parameterstestis

Identifiers

PMID34681817
PMCPMC8538347
OpenAlexW3206071721

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.