Evidence map›Paper›PMID 39312692›Full record

ArticleMolecular human reproduction2024

Sperm-carried IGF2: towards the discovery of a spark contributing to embryo growth and development.

Rossella Cannarella, Oliver J Rando, Rosita A Condorelli, Sandrine Chamayou, Simona Romano, Antonino Guglielmino, Qiangzong Yin, Tobias Gustafsson Hans, Francesca Mancuso, Iva Arato and 5 more

Abstract read
In one paragraph

Article in Molecular human reproduction, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Observational
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

15 authors.

Rossella CannarellaDepartment of Clinical and Experimental Medicine, University of Catania, Catania, Italy.ORCID 0000-0003-4599-8487
Oliver J RandoDepartment of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Rosita A CondorelliDepartment of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
Sandrine ChamayouCentro HERA-Unità di Medicina della Riproduzione, Catania, Italy.
Simona RomanoCentro HERA-Unità di Medicina della Riproduzione, Catania, Italy.
Antonino GuglielminoCentro HERA-Unità di Medicina della Riproduzione, Catania, Italy.
Qiangzong YinDepartment of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Tobias Gustafsson HansDepartment of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Francesca MancusoDepartment of Medicine and Surgery, University of Perugia, Perugia, Italy.
Iva AratoDepartment of Medicine and Surgery, University of Perugia, Perugia, Italy.
Catia BellucciDepartment of Medicine and Surgery, University of Perugia, Perugia, Italy.
Giovanni LucaDepartment of Medicine and Surgery, University of Perugia, Perugia, Italy.
Scott D LundyGlickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
Sandro La VigneraDepartment of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
Aldo E CalogeroDepartment of Clinical and Experimental Medicine, University of Catania, Catania, Italy.

Funding

American Society for Reproductive Medicine
6 · The paper itself

Abstract

Spermatozoa have been shown to carry key RNAs which, according to animal evidence, seem to play a role in early embryo development. In this context, a potential key growth regulator is insulin-like growth factor 2 (IGF2), a highly conserved paternally expressed imprinted gene involved in cell growth and proliferation which, recent observations indicate, is expressed in human spermatozoa. We herein hypothesized that sperm IGF2 gene expression and transmission at fertilization is required to support early embryo development. To test this hypothesis, we analyzed sperm IGF2 mRNA levels in the same semen aliquot used for homologous assisted reproductive technique (ART) in infertile couples and correlated these levels with embryo morphokinetics. To find a mechanistic explanation for the observed results, the transcriptomes of blastocysts obtained after injection of Igf2 mRNA in mouse parthenotes were analyzed. Sperm IGF2 mRNA negatively correlated with time of 2-cell stage (t2), t3, t4, t5, and time of expanded blastocyst (tEB), independently of maternal age, body mass index, anti-Müllerian hormone levels, and oocyte quality. An IGF2 mRNA index >4.9 predicted the ability of the embryos to reach the blastocyst stage on Day 5, with a sensitivity of 100% and a specificity of 71.6% (AUC 0.845; P < 0.001). In the animal study, transcriptome analysis demonstrated that 65 and 36 genes were, respectively, up- and down-regulated in the experimental group compared to the control group. These genes belong to pathways that regulate early embryo development, thus supporting the findings found in humans. This study has the potential to challenge the longstanding tenet that spermatozoa are simply vehicles carrying paternal DNA. Instead, it suggests that IGF2 mRNA in healthy spermatozoa provides critical support for early embryo development. Pre-ART sperm-carried IGF2 mRNA levels may be used as a marker to predict the chances of obtaining blastocysts to be transferred for infertile couples undergoing ART.

Indexed as

BlastocystEmbryonic DevelopmentInsulin-Like Growth Factor IISpermatozoaAdultAnimalsFemaleGene Expression Regulation, DevelopmentalHumansMaleMiceRNA, MessengerIGF2 protein, humanInsulin-Like Growth Factor IIRNA, Messengerblastocystembryo developmentembryo kineticsembryo morphologyIGF2sperm IGF2

Identifiers

PMID39312692
PMCPMC11975288

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Registered trials

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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.