Diabetic Embryopathy: A Developmental Perspective from Fertilization to Adulthood

Abstract

Maternal diabetes mellitus is one of the strongest human teratogens. Despite recent advances in the fields of clinical embryology, experimental teratology and preventive medicine, diabetes-related perturbations of the maternofetal unit maintain a considerable impact on the Healthcare System. Classic consequences of prenatal exposure to hyperglycemia encompass (early) spontaneous abortions, perinatal death and malformations. The spectrum of related malformations comprises some recurrent blastogenic monotopic patterns, i.e. holoprosencephaly, caudal dysgenesis and oculoauriculovertebral spectrum, as well as pleiotropic syndromes, i.e. femoral hypoplasia-unusual face syndrome. Despite this, most malformed fetuses display multiple blastogenic defects of the VACTERL type, whose (apparently) casual combination preclude recognizing recurrent patterns, but accurately testifies to their developmental stage at onset. With the application of developmental biology in modern medicine, the effects of diabetes on the unborn patient are expanded to include the predisposition to develop insulin resistance in adulthood. The mechanisms underlying the transgenerational correlation between maternal diabetes and proneness to adult disorders in the offspring remain unclear, and the epigenetic plasticity may represent the missing link. In this scenario, a development-driven summary of the multifaced consequences of maternal diabetes on fertility and child health may add a practical resource to the repertoire of available information on early stages of embryogenesis.

An Approach to the Identification of Anomalies and Etiologies in Neonates with Identified or Suspected VACTERL (Vertebral Defects, Anal Atresia, Tracheo-Esophageal Fistula with Esophageal Atresia, Cardiac Anomalies, Renal Anomalies, and Limb Anomalies) Association

“…7, 54–56 Although VACTERL association is usually sporadic, a relatively small number of familial cases have been described, and there may be an over-representation of VACTERL-type anomalies in relatives of probands. 57, 58 A thorough family history can help with the differential diagnosis (e.g., the possibility of other conditions may be raised) and can help inform discussions regarding recurrence risks.…”

Hyperglycemia impairs left–right axis formation and thereby disturbs heart morphogenesis in mouse embryos

“…Of note, we also found that the somites of high-glucose embryos are smaller along the anteroposterior axis compared with those in control embryos. The smaller somites observed in high-glucose embryos might possibly be related to the observation that the risk for costovertebral defects and VACTERL (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities) is increased in human diabetic embryopathy (52). Somitogenesis is regulated by oscillation of Notch signaling in presomitic mesoderm (49).…”

Femoral–facial syndrome in an infant of a diabetic mother

“…FFS has a strong association with maternal diabetes, and maternal hyperglycaemia is one of the strongest human teratogens 7. Most of the congenital malformations occurring in infants of diabetic mothers are blastogenic in origin,4 which can result in a significantly higher risk for congenital malformations including neural tube defects, caudal dysgenesis, congenital heart defects, renal anomalies and femoral hypoplasia.…”