Plat safeguards maternally aged oocytes against programmed cell death through activating the Erk1/2 pathway

Xingsi He1,2, Hanwen Zhang1,2, Ya Wang1,3

  • 1State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Clinical Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, 211166, China.

PubMed

Insights

Female reproductive aging impairs oocyte quality. This study reveals tissue-type plasminogen activator (tPA) protects aged oocytes from cell death, suggesting tPA supplementation could improve fertility.

Area of Science:

  • Reproductive Biology
  • Cellular Aging
  • Molecular Mechanisms of Aging

Background:

  • Female reproductive aging is linked to decreased oocyte quality and developmental potential.
  • The precise molecular mechanisms driving these age-related declines remain poorly understood.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying oocyte quality decline in aged females.
  • To identify potential therapeutic targets for improving aged oocyte quality.

Main Methods:

  • Integrative analysis of transcriptomes and morphologies of individual oocytes from young and aged mice.
  • Investigated the roles of apoptotic and ferroptotic pathways.
  • Examined the function of the Plat gene and its product, tissue-type plasminogen activator (tPA).
  • Assessed the impact of tPA supplementation on oocyte maturation in vitro.

Main Results:

  • Morphologically defective aged oocytes exhibit distinct transcriptomic profiles and activated apoptotic and ferroptotic pathways.
  • The Plat gene, encoding tPA, is downregulated in aged oocytes, increasing susceptibility to cell death.
  • tPA signaling through Erk1/2 pathway activation protects oocytes from programmed cell death (PCD).
  • Supplementing with exogenous tPA improved the quality and developmental potential of aged oocytes in vitro.

Conclusions:

  • Plat/tPA plays a critical role in protecting aged mouse oocytes from PCD.
  • tPA supplementation represents a potential clinical strategy to enhance oocyte quality in women of advanced maternal age.

Related Concept Videos

DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
3.0K
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.9K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.2K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.0K
Oogenesis02:07

Oogenesis

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...
68.8K
Maintenance of the ES Cell State01:14

Maintenance of the ES Cell State

The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
2.6K