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Related Experiment Video

Updated: Jul 11, 2025

Author Spotlight: Exploring the Long-Term Health Impacts of Intracytoplasmic Sperm Injection on Offspring
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Author Spotlight: Exploring the Long-Term Health Impacts of Intracytoplasmic Sperm Injection on Offspring

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Intracytoplasmic sperm injection induces transgenerational abnormalities in mice.

Mito Kanatsu-Shinohara1,2, Yusuke Shiromoto1, Narumi Ogonuki3

  • 1Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

The Journal of Clinical Investigation
|November 15, 2023
PubMed
Summary

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Mouse ICSI impairs fertility of male offspring by disruption of fetomaternal tolerance.

Development (Cambridge, England)·2026

Assisted reproductive techniques (ARTs) like in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), including spermatogonial transplantation, can cause behavioral and congenital abnormalities in offspring. These defects may appear in later generations, impacting fertility and development.

Area of Science:

  • Reproductive Biology
  • Developmental Biology
  • Genetics

Background:

  • In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are established assisted reproductive techniques (ARTs) for infertility treatment.
  • Spermatogonial transplantation is an emerging ART for fertility restoration in cancer patients.
  • The impact of germ cell manipulation via ARTs on offspring development and behavior requires investigation.

Purpose of the Study:

  • To investigate the effects of combining spermatogonial transplantation with ICSI on the behavior and development of offspring.
  • To assess whether ART-induced defects are heritable and manifest in subsequent generations.

Main Methods:

  • Production of F1 offspring using a combination of spermatogonial transplantation and ICSI.
Keywords:
BehaviorFertilityReproductive BiologyStem cells

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  • Comparison of behavioral phenotypes between spermatogonial transplantation-ICSI offspring and ICSI-only control offspring.
  • Generation of F2 offspring through in vitro fertilization (IVF) using sperm from F1 generation mice to evaluate germline transmission of defects.

    • Main Results:

    • Both spermatogonial transplantation-ICSI and ICSI-only mice exhibited behavioral abnormalities, persisting into the F2 generation.
    • F2 offspring derived from F1 sperm showed significant congenital abnormalities, including anophthalmia, hydrocephalus, and limb defects.
    • ARTs can induce morphological and functional defects in mice, with some becoming apparent only after germline transmission.

    Conclusions:

    • Assisted reproductive techniques, including spermatogonial transplantation and ICSI, can lead to behavioral and developmental abnormalities in offspring.
    • These ART-induced defects can be transmitted through the germline, affecting subsequent generations.
    • Further research is needed to understand the mechanisms underlying ART-induced defects and ensure the safety of these technologies.