Related Experiment Video

Updated: Mar 11, 2026

Whole Ovary Immunofluorescence, Clearing, and Multiphoton Microscopy for Quantitative 3D Analysis of the Developing Ovarian Reserve in Mouse
12:36

Whole Ovary Immunofluorescence, Clearing, and Multiphoton Microscopy for Quantitative 3D Analysis of the Developing Ovarian Reserve in Mouse

Published on: September 3, 2021

5.5K

Mouse Double Minute 2 Actively Suppresses p53 Activity in Oocytes during Mouse Folliculogenesis

Chen-Xi Zhang1, Qin Zhang2, Yin-Yin Xie1

  • 1State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing, China.

The American Journal of Pathology
|December 3, 2016
PubMed

Insights

Mouse double minute 2 (MDM2) is crucial for oocyte survival by regulating p53. Its deletion causes premature ovarian failure, highlighting MDM2

Area of Science:

  • Molecular Biology
  • Reproductive Biology
  • Oncology

Background:

  • The p53 signaling network is vital for cellular stress responses and tumor suppression.
  • Negative regulation of p53 by mouse double minute 2 (MDM2) and MDM4 is critical for development and homeostasis.
  • The specific role of MDM2 in regulating p53 and stress responses in female germ cells is not well understood.

Purpose of the Study:

  • To investigate the regulatory role of MDM2 on p53 and stress responses in mouse oocytes.
  • To determine the impact of MDM2 deletion on female fertility and ovarian function.
  • To elucidate the prosurvival mechanisms of MDM2 in oocytes under stress.

Main Methods:

  • Utilized the Cre-loxP system for targeted deletion of Mdm2 in mouse oocytes at various folliculogenesis stages.
  • Assessed p53 nuclear accumulation, oocyte viability, and fertility following Mdm2 deletion.
  • Employed concurrent deletion of p53 and treatment with Nutlin-3, 5-fluorouracil, and doxorubicin to evaluate p53-dependent effects.

Main Results:

  • Mdm2 deletion in oocytes led to significant p53 nuclear accumulation and impaired fertility, characterized by early follicular loss.
  • These phenotypes were fully rescued by concurrent deletion of p53, confirming a p53-dependent mechanism.
  • Inhibition of MDM2-p53 binding (Nutlin-3) induced p53-dependent oocyte death, while certain chemotherapeutics activated p53 in Mdm2/Mdm4 heterozygous oocytes.

Conclusions:

  • MDM2 plays a critical prosurvival role in oocytes, essential for maintaining ovarian function.
  • The MDM2/MDM4-p53 regulatory network in female germ cells operates under a stringent mode during stress.
  • These findings suggest MDM2 as a potential target for conditions related to premature ovarian failure.

More Related Videos

Defining the Program of Maternal mRNA Translation during In vitro Maturation using a Single Oocyte Reporter Assay08:00

Defining the Program of Maternal mRNA Translation during In vitro Maturation using a Single Oocyte Reporter Assay

Published on: June 16, 2021

4.8K
Mouse Oocyte Microinjection, Maturation and Ploidy Assessment07:03

Mouse Oocyte Microinjection, Maturation and Ploidy Assessment

Published on: July 23, 2011

30.9K

Related Concept Videos

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...
5.4K
Meiosis II02:02

Meiosis II

Meiosis II entails cell division and segregation of the sister chromatids, resulting in the production of four unique haploid gametes. The steps for meiosis II are similar to mitosis, except that meiosis II occurs in haploid cells, whereas mitosis occurs in diploid cells.
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
51.3K
Meiosis II01:57

Meiosis II

Meiosis II is the second and final stage of meiosis. It relies on the haploid cells produced during meiosis I, each of which contain only 23 chromosomes—one from each homologous initial pair. Importantly, each chromosome in these cells is composed of two joined copies, and when these cells enter meiosis II, the goal is to separate such sister chromatids using the same microtubule-based network employed in other division processes. The result of meiosis II is two haploid cells, each...
209.8K
Oogenesis01:22

Oogenesis

Oogenesis,  the process of developing egg cells (female gametes), occurs within the ovaries and is fundamental to female fertility. This sequence begins during fetal development when diploid oogonia in the developing ovaries undergo mitotic divisions to produce primary oocytes. By birth, these primary oocytes enter prophase I of meiosis but become arrested in this stage, remaining suspended until puberty.
Each primary oocyte is surrounded by a layer of pre-granulosa cells, forming what is...
4.6K
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...
70.9K