In vitro fertilization-conceived offspring exhibit altered Long Interspersed Nuclear Elements-1 retrotransposition...

Area of Science:

• Reproductive Medicine
• Genomics
• Epigenetics

Background:

• Assisted reproductive technologies like in vitro fertilization (IVF) are associated with increased risks of long-term health conditions in offspring.
• The underlying molecular mechanisms for these increased risks remain largely unclear.
• Long Interspersed Nuclear Elements-1 (L1), mobile genetic elements sensitive to environmental stress, are investigated as potential mediators of these risks.

Purpose of the Study:

• To test the hypothesis that IVF procedures induce embryonic stress, altering L1 dynamics.
• To investigate if altered L1 dynamics contribute to genomic instability and subsequent long-term disease susceptibility in IVF offspring.
• To explore the link between IVF, L1 elements, and disease risk.

Main Methods:

• Whole genome sequencing was performed on umbilical cord blood or peripheral blood from 33 IVF and 42 naturally conceived (NC) neonates.
• Bioinformatic tools (Bowtie2, MELT) were used to quantify L1 content and detect de novo L1 insertions and deletions.
• Three parent-matched IVF-NC sibling pairs were analyzed to control for genetic background, and disease association analysis was conducted for genes near differential L1 sites.

Main Results:

• IVF offspring exhibited significantly elevated global L1 content compared to NC controls (P=0.04).
• This finding was confirmed in sibling pairs, with IVF-conceived children showing higher L1 levels than their NC siblings.
• Differential L1 insertion (11 loci) and deletion (14 loci) frequencies were identified between IVF and NC groups, with enrichment near genes associated with metabolic, cardiovascular, neuropsychiatric, and neoplastic diseases.

Conclusions:

• IVF conception is associated with increased L1 content and altered genomic distribution of L1 elements.
• The proximity of these differential L1 sites to disease-associated genes suggests a potential genomic mechanism linking IVF-associated embryonic stress to elevated disease risk.
• These findings offer molecular insights into assisted reproductive technology safety and highlight the importance of monitoring genomic integrity in IVF-conceived individuals.