Advanced Maternal Age Differentially Affects Embryonic Tissues with the Most Severe Impact on the Developing Brain
Caroline Kokorudz1,2, Bethany N Radford1,2, Wendy Dean2,3
1Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada.
Cells
|January 8, 2023
Summary
Advanced maternal age (AMA) increases pregnancy risks, impacting placental development and fetal neurodevelopment. Even healthy-appearing embryos from older mothers show altered brain gene expression, suggesting lifelong consequences.
Area of Science:
- Reproductive biology
- Developmental biology
- Genomics
Background:
- Advanced maternal age (AMA) is a significant risk factor for pregnancy complications.
- AMA affects oocyte quality and can lead to placental defects.
- Placental abnormalities are linked to fetal brain and cardiovascular issues.
Purpose of the Study:
- To investigate the impact of AMA on fetal development.
- To compare transcriptomes of placentas, brains, hearts, and facial prominences in conceptuses from young and aging female mice.
- To identify specific developmental pathways affected by AMA.
Main Methods:
- Comparative transcriptome analysis of multiple fetal tissues from young and aging mouse mothers.
- Utilizing trophoblast stem cells (TSCs) to model placental development.
- Exposure of TSCs to conditioned medium from aging uterine stromal cells.
Main Results:
- AMA increases transcriptional heterogeneity across all examined fetal tissues, most notably in the brain.
- Significant expression changes in neurodevelopmental genes were observed in fetuses from older mothers, irrespective of apparent normalcy.
- Aging uterine stromal cell-conditioned medium impaired TSC proliferation and induced precocious differentiation, mimicking placental defects.
Conclusions:
- AMA poses substantial risks to reproductive outcomes, with neurodevelopment being particularly vulnerable.
- Placental defects arising from AMA likely contribute to observed neurodevelopmental alterations.
- These early developmental perturbations due to AMA may have long-lasting effects on offspring health.
Related Concept Videos
02:07Oogenesis
64.0K
In human women, oogenesis produces one mature egg cell or ovum for every precursor cell that enters meiosis. This process differs in two unique ways from the equivalent procedure of spermatogenesis in males. First, meiotic divisions during oogenesis are asymmetric, meaning that a large oocyte (containing most of the cytoplasm) and minor polar body are produced as a result of meiosis I, and again following meiosis II. Since only oocytes will go on to form embryos if fertilized, this unequal...
64.0K
02:57Meiosis vs. Mitosis
57.4K
Cell division is necessary for growth and reproduction in organisms. Mitosis aids cell growth and development by dividing somatic cells. In contrast, meiosis causes the division of germ cells and plays an essential role in sexual reproduction. Due to their unique functional requirements, mitosis and meiosis differ from each other in multiple aspects.
Before the start of mitosis and meiosis I, the cell synthesizes DNA, resulting in two homologous copies of each chromosome. DNA synthesis is...
Before the start of mitosis and meiosis I, the cell synthesizes DNA, resulting in two homologous copies of each chromosome. DNA synthesis is...
57.4K
01:07Teratogenicity
2.6K
The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
2.6K
01:21Nondisjunction
3.9K
Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate correctly and move to the opposite poles of the cells. This produces daughter cells with abnormal chromosome numbers. Nondisjunction is common during anaphase I or anaphase II of meiosis. Mutations in synaptonemal complex proteins that attach homologous chromosomes increase the chances of nondisjunction in anaphase I of meiosis I. In contrast, mutations in topoisomerases and condensins that hold...
3.9K