Unknown

Dataset Information

0

Maternal diabetes causes developmental delay and death in early-somite mouse embryos.


ABSTRACT: Maternal diabetes causes congenital malformations and delays embryonic growth in the offspring. We investigated effects of maternal diabetes on mouse embryos during gastrulation and early organogenesis (ED7.5-11.5). Female mice were made diabetic with streptozotocin, treated with controlled-release insulin implants, and mated. Maternal blood glucose concentrations increased up to embryonic day (ED) 8.5. Maternal hyperglycemia induced severe growth retardation (approx.1?day) in 53% of the embryos on ED8.5, death in most of these embryos on ED9.5, and the termination of pregnancy on ED10.5 in litters with >20% dead embryos. Due to this selection, developmental delays and reduction in litter size were no longer observed thereafter in diabetic pregnancies. Male and female embryos were equally sensitive. High-throughput mRNA sequencing and pathway analysis of differentially expressed genes showed that retarded embryos failed to mount the adaptive suppression of gene expression that characterized non-retarded embryos (cell proliferation, cytoskeletal remodeling, oxidative phosphorylation). We conclude that failure of perigastrulation embryos of diabetic mothers to grow and survive is associated with their failure to shut down pathways that are strongly down-regulated in otherwise similar non-retarded embryos. Embryos that survive the early and generalized adverse effect of maternal diabetes, therefore, appear the subset in which malformations become manifest.

SUBMITTER: Zhao J 

PROVIDER: S-EPMC5601907 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

Maternal diabetes causes developmental delay and death in early-somite mouse embryos.

Zhao Jing J   Hakvoort Theodorus B M TBM   Ruijter Jan M JM   Jongejan Aldo A   Koster Jan J   Swagemakers Sigrid M A SMA   Sokolovic Aleksandar A   Lamers Wouter H WH  

Scientific reports 20170915 1


Maternal diabetes causes congenital malformations and delays embryonic growth in the offspring. We investigated effects of maternal diabetes on mouse embryos during gastrulation and early organogenesis (ED7.5-11.5). Female mice were made diabetic with streptozotocin, treated with controlled-release insulin implants, and mated. Maternal blood glucose concentrations increased up to embryonic day (ED) 8.5. Maternal hyperglycemia induced severe growth retardation (approx.1 day) in 53% of the embryos  ...[more]

Similar Datasets

| S-EPMC5886049 | biostudies-literature
| S-EPMC3637269 | biostudies-literature
| S-EPMC6769302 | biostudies-literature
| S-EPMC7691497 | biostudies-literature
| S-EPMC4104679 | biostudies-literature
| S-EPMC2867389 | biostudies-literature
| S-EPMC6811537 | biostudies-literature
| S-EPMC6906334 | biostudies-literature
| S-EPMC5502304 | biostudies-literature
| S-EPMC6940819 | biostudies-literature