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d-galactose causes embryonic development arrest and placental development disorders in mice by increasing ROS and
Lanlan Yin1, Yanru Niu2, Xiudan Zheng1
1Reproductive Medicine Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.
Introduction:
Does an elevation in d-Galactose (D-Gal) levels within the body contribute to abnormal embryonic development and placental dysfunction during pregnancy?
Methods:
Mouse embryos were cultivated to the blastocyst stage under varying concentrations of D-Gal. The blastocyst formation rate was measured, and the levels of reactive oxygen species (ROS), sirtuin 1 (SIRT1), and forkhead box O3a (FOXO3a) in blastocysts were assessed. Mice were intraperitoneally injected with either saline or D-Gal with or without SRT1720. On the 14th day of pregnancy, the fetal absorption rate and placental weight were recorded. Placental levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were determined. The expression of senescence-related factors, such as senescence-associated β-galactosidase (SA-β-gal) in the placenta was examined, and the expression of placental SIRT1, FOXO3a and p21 was evaluated by immunohistochemistry and Western blotting.
Results:
D-Gal adversely affects early embryonic development in vitro, resulting in a decreased blastocyst formation rate. Furthermore, D-Gal downregulates SIRT1 and FOXO3a while increasing ROS levels in blastocysts. Concurrently, D-Gal induces placental dysfunction, characterized by an elevated fetal absorption rate, reduced placental weight, diminished SOD activity, and increased MDA content. The senescence-related factor SA-β-gal was detected in the placenta, along with altered expression of placental SIRT1, FOXO3a, and p21. The SIRT1 agonist SRT1720 mitigated this damage by increasing SIRT1 and FOXO3a expression.
Discussion:
The inhibition of early embryonic development and placental dysfunction induced by D-Gal may be attributed to the dysregulation of SIRT1. Activating SIRT1 emerges as a potentially effective strategy for alleviating the adverse effects of D-Gal exposure.
Insights
Elevated d-Galactose (D-Gal) impairs embryonic development and causes placental dysfunction by downregulating SIRT1. Activating SIRT1 may protect against D-Gal toxicity during pregnancy.
Area of Science:
- Reproductive biology
- Developmental toxicology
- Molecular biology
Background:
- Elevated d-Galactose (D-Gal) levels are implicated in various health issues.
- The impact of D-Gal on embryonic development and placental function requires further investigation.
- Sirtuin 1 (SIRT1) plays a crucial role in cellular regulation and stress response.
Purpose of the Study:
- To investigate the effects of elevated d-Galactose on early embryonic development and placental function in a mouse model.
- To explore the role of SIRT1 in mediating d-Galactose-induced toxicity.
- To evaluate the potential of SIRT1 activation as a therapeutic strategy.
Main Methods:
- Mouse embryos were cultured in vitro with varying d-Galactose concentrations.
- In vivo studies involved D-Galactose administration to pregnant mice, with or without a SIRT1 agonist (SRT1720).
- Embryonic development, blastocyst formation rates, fetal absorption, placental weight, oxidative stress markers (ROS, SOD, MDA), and senescence markers (SA-β-gal, p21) were assessed.
Main Results:
- D-Galactose exposure decreased blastocyst formation rates in vitro and impaired embryonic development.
- In vivo, D-Galactose led to increased fetal absorption, reduced placental weight, elevated oxidative stress, and signs of placental senescence.
- D-Galactose downregulated SIRT1 and FOXO3a expression in blastocysts and altered their expression in the placenta.
- Treatment with the SIRT1 agonist SRT1720 ameliorated D-Galactose-induced embryonic and placental damage.
Conclusions:
- D-Galactose negatively impacts early embryonic development and placental function, potentially through SIRT1 dysregulation.
- SIRT1 activation demonstrates a protective effect against D-Galactose toxicity.
- Targeting SIRT1 may offer a therapeutic avenue to mitigate adverse pregnancy outcomes associated with elevated D-Galactose levels.
