Intracytoplasmic sperm injection induces transgenerational abnormalities in mice

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.
• 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.