Adenoviral supply of active transforming growth factor-beta1 (TGF-beta1) did not prevent lethality in transforming

H Chagraoui1, S Giraudier, W Vainchenker

  • 1INSERM U. 362, Institut Gustave-Roussy, PR1, 39, rue Camille-Desmoulins, 94805 Villejuif, France. hchagra@igr.fr

European Cytokine Network
|January 10, 2002
PubMed

Insights

Maternal transforming growth factor-beta1 (TGF-beta1) administration did not rescue TGF-beta1-null embryos from embryonic lethality. Despite efficient maternal-fetal transfer, elevated TGF-beta1 levels failed to prevent developmental death in knockout conceptuses.

Area of Science:

  • Developmental Biology
  • Immunology
  • Genetics

Background:

  • Transforming growth factor-beta1 (TGF-beta1) is crucial for embryonic development.
  • TGF-beta1-null conceptuses exhibit embryonic lethality, influenced by genetic background.
  • Maternal TGF-beta1 transfer has been proposed as a rescue mechanism for TGF-beta1-null embryos.

Purpose of the Study:

  • To investigate if increased maternal TGF-beta1 during pregnancy can rescue TGF-beta1-null embryos from embryonic lethality.
  • To determine the efficacy of transplacental transfer of an active form of TGF-beta1.

Main Methods:

  • Utilized an adenovirus-based gene delivery system (Ad-TGF-beta1S223/S225) in mice.
  • Administered TGF-beta1 via intravenous injection to pregnant dams.
  • Measured TGF-beta1 levels in maternal plasma and embryonic tissues.
  • Assessed the frequency of TGF-beta1-null neonates and conceptuses at different developmental stages.

Main Results:

  • A single Ad-TGF-beta1 injection induced a 20-fold increase in maternal plasma TGF-beta1 for up to 3 months.
  • Elevated TGF-beta1 levels were detected in embryos from treated mothers, indicating maternal-fetal transfer.
  • No increase in TGF-beta1-null neonates or conceptuses was observed despite TGF-beta1 administration throughout gestation.
  • High plasma TGF-beta1 levels resulted partly from stimulated autocrine production.

Conclusions:

  • Transplacental passage of TGF-beta1 was ineffective in rescuing TGF-beta1-null conceptuses from embryonic lethality.
  • Maternal TGF-beta1 supplementation does not overcome embryonic lethality in TGF-beta1-null mice.
  • The study highlights the complex role of TGF-beta1 in embryonic development and maternal-fetal interactions.

Related Concept Videos

Factors Influencing Microbial Growth: Osmolarity01:28

Factors Influencing Microbial Growth: Osmolarity

Osmolarity is the measure of solute concentration in a solution. It plays a critical role in determining water availability for organisms. Water moves across semipermeable membranes through osmosis, flowing from regions of lower solute concentration (more dilute) to regions of higher solute concentration (more concentrated).In high-solute environments, microbial cells lose water, leading to dehydration and inhibited growth. The extent to which water is available to microbes in such environments...
961
Factors Influencing Microbial Growth: Temperature01:27

Factors Influencing Microbial Growth: Temperature

Microorganisms display remarkable adaptations, enabling them to thrive in diverse ecological niches across a wide range of temperatures. Temperature profoundly influences microbial growth by affecting enzymatic activity, membrane fluidity, and other cellular processes.Each microorganism operates within a specific temperature range defined by three cardinal points: minimum, optimum, and maximum. Below the minimum temperature, membranes lose fluidity, halting transport processes. Above the...
1.4K
Factors Influencing Microbial Growth: pH01:29

Factors Influencing Microbial Growth: pH

Microorganisms are classified as acidophiles, neutrophiles, or alkaliphiles based on their pH growth preferences, reflecting their adaptations to specific environments. Maintaining a stable intracellular pH is critical for macromolecular stability and enzymatic activity, which can be challenged by external pH variations.Neutrophiles, such as Escherichia coli, grow optimally between pH 5.5 and 8.0. These microorganisms inhabit neutral or slightly acidic environments and employ mechanisms like...
1.3K
Role of Hematopoietic Growth Factors01:28

Role of Hematopoietic Growth Factors

Hematopoietic growth factors are molecules that regulate the differentiation rate of hematopoietic stem cells (HSCs). Erythropoietin (EPO), primarily produced by the kidneys, plays a crucial role in erythrocyte production. When oxygen levels in the blood are low, EPO is released into the bloodstream, reaching the bone marrow, where it stimulates HSCs to differentiate and mature into erythrocytes, which are vital for oxygen transport.
Thrombopoietin (TPO), mainly released by the liver,...
4.0K
Bacterial Transformation01:33

Bacterial Transformation

In 1928, bacteriologist Frederick Griffith worked on a vaccine for pneumonia, which is caused by Streptococcus pneumoniae bacteria. Griffith studied two pneumonia strains in mice: one pathogenic and one non-pathogenic. Only the pathogenic strain killed host mice.
Griffith made an unexpected discovery when he killed the pathogenic strain and mixed its remains with the live, non-pathogenic strain. Not only did the mixture kill host mice, but it also contained living pathogenic bacteria that...
60.1K
Population Growth00:57

Population Growth

Population size is dynamic, increasing with birth rates and immigration, and decreasing with death rates and emigration. In ideal conditions with unlimited resources, populations can increase exponentially, which plots as a J-shaped growth rate curve of population size against time. This type of curve is characteristic of newly-introduced invasive species, or populations that have suffered catastrophic declines and are rebounding.
28.7K