Gynecological Endocrinology, 2012; Early Online: 1–4 © 2012 Informa UK, Ltd. ISSN 0951-3590 print/ISSN 1473-0766 online DOI: 10.3109/09513590.2012.736556 Mitochondrial activity is critical for maintenance of correct glucose homeostasis and alteration in mitochondrial content or function may progressively lead to the development of insulin resistance. Evidence on the possible role of mitochondria in the pathogenesis of gestational diabetes mellitus (GDM) is conversely scanty and inconsistent. The aim was to evaluated mitochondrial DNA (mtDNA) content in peripheral blood of pregnant women with GDM. We selected 25 pregnant women affected by GDM and 50 controls with physiological pregnan- cies. A blood sample was collected at 32–36 weeks’ gestation, stored and thawed simultaneously. The mtDNA content was determined utilizing a quantitative real-time polymerase chain reaction by the Taqman method, using a genomic control and a target gene. Results are expressed as copy number per nuclear DNA. The median (interquartile range) mtDNA content in GDM and controls was 122 (107–198) and 170 (129–196), respec- tively (p = 0.039). The mtDNA content was also correlated to GDM treatment, self-blood glucose monitoring and newborns’ weight, but these analyses failed to document any statistically significant association. Attenuated mitochondrial function may play a role in the development of GDM. Further experiments are required to definitely clarify whether this defect represents a primary event in the pathogenesis of the disease. Keywords: Gestational diabetes mellitus, insulin resistance, mitochondria, mitocondria DNA content, pregnancy Introduction Gestational diabetes mellitus (GDM) is a common complication of pregnancy determining increasing risks to the mother, the growing fetus and the future child. It is deined as carbohydrate intolerance with onset or irst recognition during gestation [1]. Pregnancy represents a stressful condition for glucose homeo- stasis and women with an occult insulin resistance unremark- able in a non-pregnant state may transiently develop this form of diabetes during the gestational period. In fact, GDM shares a common pathophysiological background with type 2 diabetes mellitus (T2DM). Several epidemiological studies showed that women with GDM are at increased risk to develop T2DM later in their life [2]. here is growing evidence suggesting that mitochondrial content or function is altered in patients with insulin resistance and T2DM [3,4]. It has been proposed that mitochondria would play a critical primary role in the establishment of insulin resis- tance and subsequent diabetes development [3]. he emerging view is that an attenuated mitochondrial activity in the adipo- cytes has a detrimental efect on the metabolism of fatty acids, altering their storage in the cell in the form of triacylglicerole and determining their release into the blood stream. Once reaching the circulation, fatty acids may deposit in ectopic sites such skeletal muscles and liver and herein progressively display their potent capacity to induce insulin resistance. In a latter phase of the disease, fatty acids also damage pancreatic beta cells leading to manifest T2DM. Despite a large body of evidence documenting that some muta- tions in genes encoding mitochondrial components or a reduced mitochondrial content are associated with an enhanced risk for the development of T2DM [3], data on GDM is in contrast scanty and inconsistent. Chen et al. reported that mitochondrial DNA (mtDNA) mutations that alter mitochondrial function may contribute to the development of GDM [5], but this was not conirmed in other reports [6,7]. To the best of our knowledge, there is no study in the literature aimed at determining peripheral mitochondrial content in women with GDM. To elucidate this aspect, we evaluated mtDNA, an accepted surrogate measure of mitochondrial content, in peripheral blood of pregnant women with GDM. Methods Patients his case-control study was performed at the Obstetrics and Gynecology Institute of the Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy. Women referred between January to May 2011 to the outpatient department unit of diabetes in pregnancy with the diagnosis of GDM were considered for study entry. he diagnosis of GDM was in accordance with the new diagnostic criteria [8]. he control group consisted of women referring to our Institution during the same study period for physiological pregnancies. he inclusion criteria for both study groups were as follows: age <45 years, singleton pregnancy, Caucasian ethnicity, gestational age 32–36 weeks, absence of maternal or fetal pathologies. Exclusion criteria were as follows: past or present smoking, alcohol abuse, drug addition, type 1 diabetes mellitus (T1DM), T2DM or overt diabetes testing earlier in the index pregnancy and intrauterine growth restriction (IUGR). Women with a history of GDM in previous pregnancies and those who did not undergo screening for GDM at 24–28 weeks’ gestations were exclusion criteria for controls. Women fulilling these criteria were invited to participate in this study. If consenting, they were requested to give an informed and written ORIGINAL ARTICLE A role for mitochondria in gestational diabetes mellitus? Francesca Crovetto 1,2 , Debora Lattuada 1 , Gabriele Rossi 1 , Sveva Mangano 1,2 , Edgardo Somigliana 1 , Giorgio Bolis 1,2 & Luigi Fedele 1,2 1 Department of Obstetrics and Gynecology, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy and 2 Università degli Studi di Milano, Milan, Italy Correspondence: Francesca Crovetto, Department Obstet Gynecol, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy. Tel: +39-338-6082204. Fax: +39-02-50320252. E-mail: franci.crovetto@gmail.com or francesca.crovetto@studenti.unimi.it Gynecol Endocrinol Downloaded from informahealthcare.com by Libreria Joaquin Ibanez on 11/20/12 For personal use only.