Related Experiment Video
Updated: Jun 12, 2026
Bioluminescent Monitoring of Graft Survival in an Adoptive Transfer Model of Autoimmune Diabetes in Mice
Published on: November 18, 2022
Transgenic mice overproducing human thioredoxin-1, an antioxidative and anti-apoptotic protein, prevents diabetic
Y Kamimoto1, T Sugiyama, T Kihira
1Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Aims/Hypothesis:
Experimental studies have suggested that apoptosis is involved in diabetic embryopathy through oxidative stress. However, the precise mechanism of diabetic embryopathy is not yet clear. Thioredoxin (TRX) is a small, ubiquitous, multifunctional protein, which has recently been shown to protect cells from oxidative stress and apoptosis. Using transgenic mice that overproduce human TRX-1 (TRX-Tg mice), we examined whether oxidative stress is involved in fetal dysmorphogenesis in diabetic pregnancies.
Methods:
Non-diabetic and streptozotocin-induced diabetic (DM) female mice were mated with male TRX-Tg mice. Pregnant mice were killed either at day 10 or day 17 of gestation, and viable fetuses and their placentas were recovered, weighed and assessed for gross and histological morphology, biochemical markers and gene expression.
Results:
In both wild-type (WT) and transgenic (Tg) groups, fetal and placental weights in the diabetic group were significantly decreased compared with the non-diabetic group. The incidence of malformation was higher in the diabetic group, and was significantly decreased in the TRX-Tg group (DM-WT vs DM-Tg; 28.6% vs 10.4%). Oxidative stress markers such as thiobarbituric acid reactive substances and 8-hydroxy-2'-deoxyguanosine were increased in DM-WT group fetuses but were decreased in fetuses from the DM-Tg group. Furthermore, immunohistochemically assayed apoptosis and cleaved caspase-3 production in embryonic neuroepithelial cells was significantly increased in the DM-WT group, and was significantly decreased in the DM-Tg group.
Conclusions/Interpretation:
These results indicate that oxidative stress is involved in diabetic embryopathy, and that the antioxidative protein TRX at least partially prevents diabetic embryopathy via suppression of apoptosis.
Insights
Diabetic embryopathy, a condition causing fetal malformations, is linked to oxidative stress. Overexpressing the antioxidant Thioredoxin (TRX) in mice significantly reduced these malformations and apoptosis, suggesting TRX
Area of Science:
- Developmental Biology
- Reproductive Medicine
- Biochemistry
Background:
- Diabetic embryopathy is a serious complication of diabetes in pregnancy, leading to fetal malformations.
- Oxidative stress is implicated in the pathogenesis of diabetic embryopathy, but precise mechanisms remain unclear.
- Thioredoxin (TRX) is a key antioxidant protein that protects cells against oxidative stress and apoptosis.
Purpose of the Study:
- To investigate the role of oxidative stress in fetal dysmorphogenesis during diabetic pregnancies.
- To evaluate the protective effects of overexpressing human Thioredoxin-1 (TRX-1) in a mouse model of diabetic embryopathy.
Main Methods:
- Utilized streptozotocin-induced diabetic (DM) and non-diabetic female mice mated with wild-type (WT) or human TRX-1 transgenic (TRX-Tg) male mice.
- Assessed fetal and placental development at days 10 and 17 of gestation.
- Analyzed gross morphology, histology, oxidative stress markers (TBARS, 8-OHdG), and apoptosis markers (caspase-3).
Main Results:
- Diabetic pregnancies in both WT and TRX-Tg mice showed reduced fetal and placental weights compared to non-diabetic controls.
- The incidence of fetal malformations was significantly higher in diabetic WT mice (28.6%) compared to diabetic TRX-Tg mice (10.4%).
- TRX-Tg fetuses exhibited reduced oxidative stress and apoptosis markers compared to WT fetuses from diabetic mothers.
Conclusions:
- Oxidative stress plays a significant role in the development of diabetic embryopathy.
- Overexpression of Thioredoxin (TRX) provides a protective effect against diabetic embryopathy, at least partially by suppressing apoptosis.
- TRX represents a potential therapeutic target for mitigating the adverse effects of diabetes on embryonic development.
