Vascular placental abnormalities and newborn death in a pregnant diabetic woman with familial partial lipodystrophy type 3: A possible role for peroxisome proliferator-activated receptor γ

• Published in: Diabetes & metabolism Vol. 38; no. 4; pp. 367 - 369
• Main Authors: Castell, A.L, Hiéronimus, S, Lascols, O, Fournier, T, Fénichel, P
• Format: Journal Article
• Language: English
• Published: Paris Elsevier Masson SAS 01.10.2012; Masson
• Subjects: Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Dermatology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinology & Metabolism; Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Experimental diseases; Familial partial lipodystrophy type 3; Fatal Outcome; Female; Gene Expression Regulation, Developmental; HTA gravidique; Humans; Infant, Newborn; Insulin Resistance - genetics; Internal Medicine; Invasion trophoblastique; Lipodystrophie partielle familiale type 3; Lipodystrophy, Familial Partial - genetics; Lipodystrophy, Familial Partial - metabolism; Medical sciences; Mutation, Missense; Placenta - abnormalities; Placenta - blood supply; Placenta - metabolism; Placentation - genetics; PPAR gamma - genetics; PPAR gamma - metabolism; PPARγ insulin resistance; PPARγ insulinorésistance; Pre-Eclampsia - genetics; Pre-Eclampsia - metabolism; Preeclampsia; Pregnancy; Pregnancy in Diabetics - metabolism; Pregnancy in Diabetics - pathology; Skin involvement in other diseases. Miscellaneous. General aspects; Trophoblast invasion; Young Adult; Trophoblast invasion; Familial partial lipodystrophy type 3; Lipodystrophie partielle familiale type 3; Preeclampsia; PPARγ insulin resistance; PPARγ insulinorésistance; HTA gravidique; Invasion trophoblastique; Endocrinopathy; Human; Hypertension; Skin disease; Fetal membrane; Diabetes mellitus; Metabolic diseases; Cardiovascular disease; PPAR-γ receptor; Pregnancy; Target tissue resistance; Newborn; Placenta; Female; Insulin resistance; Lipodystrophy; Adipose tissue disorders
• ISSN: 1262-3636; 1878-1780
• DOI: 10.1016/j.diabet.2012.02.012

Abstract The peroxisome proliferator-activated receptor protein gamma (PPARγ), a nuclear receptor involved in adipocyte differentiation, energy homoeostasis and fat storage, can lead, in rare cases of coding mutations, to familial partial lipodystrophy type 3 (FPLD3) with severe insulin resistance. PPARγ is also highly expressed in the syncytiotrophoblast and extravillous cytotrophoblast cells. It has a key role in trophoblast invasion, as shown by studies in vitro, but its precise role during placentation remains to be elucidated, and fetomaternal outcomes of FPLD3 pregnancies also need to be assessed. This report is of a novel missense heterozygous mutation of PPARγ identified during pregnancy in a young diabetic woman who, at 3 weeks of amenorrhoea, prematurely delivered a baby who died 24 h later. Histopathological analysis revealed important vascular placental abnormalities. The presence of the PPARγ mutation in placental tissues in the absence of fetal malformations and maternal hypertension suggests that FPLP3 pregnancies may be at high-risk, especially if the fetus has inherited the mutation. It also supports a physiological role for PPARγ during placentation.