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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Single-nucleotide polymorphisms in the p53 pathway regulate fertility in humans
Hey-Joo Kang1, Zhaohui Feng, Yvonne Sun
1Center for Reproductive Medicine and Infertility, Weill Cornell Medical College, New York, NY 10021, USA.
Summary
The tumor suppressor protein p53 influences human fertility by affecting leukemia inhibitory factor (LIF) levels. Specific p53 pathway genetic variations (SNPs) impact in vitro fertilization (IVF) success, particularly in younger women.
Area of Science:
- Reproductive biology
- Molecular genetics
- Cancer biology
Background:
- The tumor suppressor protein p53 is vital for maternal reproduction in mice, regulating leukemia inhibitory factor (LIF) for blastocyst implantation.
- Understanding p53's role in human fertility is crucial, given its established functions in cellular processes.
Purpose of the Study:
- To investigate the impact of single-nucleotide polymorphisms (SNPs) in the p53 pathway on human fertility.
- To determine if genetic variations in p53 and its regulatory genes affect in vitro fertilization (IVF) outcomes.
Main Methods:
- Assembled a list of SNPs in the p53 pathway known to modify p53 function.
- Analyzed the association of these SNPs with fertility in human populations, including IVF patients.
- Measured LIF levels in cells with different p53 alleles.
Main Results:
- The p53 allele encoding proline at codon 72 (P72) was enriched in IVF patients and identified as a risk factor for implantation failure.
- Lower LIF levels were observed in cells with the P72 allele compared to the arginine (R72) allele.
- Enrichment of specific alleles in SNPs of LIF, Mdm2, Mdm4, and Hausp genes was noted in IVF patients.
- The influence of these SNPs on fertility was diminished in women over 35 years old.
Conclusions:
- SNPs in the p53 pathway are associated with human fertility, suggesting p53 regulates reproductive efficiency.
- These findings offer insights into the evolutionary selection of p53 pathway alleles and exemplify antagonistic pleiotropy.
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