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Analysis of Transforming Growth Factor ß Family Cleavage Products Secreted Into the Blastocoele of Xenopus laevis Embryos
Published on: July 21, 2021
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
Abstract:
In TGF-beta1-knockout mice, TGF-beta1-null conceptuses die during embryonic development with a penetrance of lethality that depends on the mouse genetic background. Studies have suggested that transplacental passage of maternal TGF-beta1 could account for the rescue of some TGF-beta1-null embryos. Herein, we have used an adenovirus-based gene delivery system and a strain of mice where most TGF-beta1-null conceptuses die prior to parturition, to investigate whether an increase in maternal TGF-beta1 during pregnancy would rescue TGF-beta1-null embryos. A single intravenous injection of an adenovirus containing a modified version of TGF-beta1 cDNA (Ad-TGF-beta1S223/S225), coding for a biologically active form of the cytokine, induced a 20-fold increase in plasma TGF-beta1 (active and latent forms) levels for up to 3 months in adult mice. Similar levels of TGF-beta1 were detected in 13-day post coïtum (dpc) embryos from Ad-TGF-beta1-treated mothers, demonstrating an efficient maternal/fetal transfer of the cytokine. However, no increase in the frequencies of TGF-beta1-null neonates nor in day 11.5 dpc TGF-beta1-null conceptuses was observed despite elevated levels of TGF-beta1 delivered throughout gestation. In addition, we show that the high levels of TGF-beta1-titrated in the plasma from Ad-TGF-beta1S223/S225-treated mice were partly the consequence of a stimulation of an autocrine production by exogenous bioactive TGF-beta1. These results indicate that transplacental passage of TGF-beta1 was not effective in rescuing TGF-beta1-null conceptuses from embryonic lethality.
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.
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