Polycystic ovary syndrome offspring display increased oxidative stress markers comparable to gestational diabetes offspring

Boutzios, Georgios; Livadas, Sarantis; Piperi, Christina; Vitoratos, N.; Adamopoulos, Christos; Hassiakos, Dimitrios; Iavazzo, Christos; Diamanti-Kandarakis, Evanthia

doi:10.1016/j.fertnstert.2012.10.050

Cited by 34 publications

(28 citation statements)

References 66 publications

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“…The present and previous studies (43,44,45,46) show that elevated androgen concentrations during pregnancy in PCOS women, do not contribute to elevated androgens in cord blood. Remarkably, Anderson and Maliqueo, as we did, also found significantly lower ADION concentrations in cord blood of female offspring of the PCOS women, as compared to the female offspring of non-PCOS women (43,45).…”

Section: Discussionsupporting

confidence: 63%

Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome

Caanen

Kuijper

Hompes

et al. 2016

European Journal of Endocrinology

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Objective: Little is known about the aetiology of polycystic ovary syndrome (PCOS). Some suggest that elevated maternal androgens during gestation play a causative role. This implies placental passage of androgens during pregnancy. The aim of this study is to compare androgen and estrogen concentrations in maternal serum during pregnancy and in umbilical cord blood, between mothers with PCOS and their offspring compared to controls. Design: Prospective case-control study. Methods: Maternal blood samples were collected around 20 weeks of gestation and at delivery. Umbilical cord blood was also taken at delivery. Androgens (testosterone (T), androstenedione (ADION), dehydroepiandrostenedione (DHEA)) and estrogens (estrone (E 1 ), estradiol (E 2 ), estriol (E 3 )) were measured using the liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. Results: At 20 weeks of gestation: T (PZ0.019) and ADION (PZ0.034) were higher in the PCOS mothers (pregnant with a girl), whereas DHEA, E 1 , E 2 , and E 3 were not different. Maternal concentration at birth: T (PZ0.004) and ADION (PZ0.009) were also higher in the subgroup of PCOS mothers that were pregnant with a girl compared to the girl pregnancy controls. DHEA, E 1 , E 2 and E 3 were not different. In umbilical cord blood, no differences were found for T, ADION, DHEA, E 2 , E 3 , and AMH between the PCOS mothers and the controls respectively. E 1 was lower in girls from PCOS mothers (PZ0.007). Conclusions: Despite elevated maternal androgen concentrations during pregnancy in PCOS mothers, offspring showed no signs of elevated androgen concentrations in cord blood at birth using the latest highly specific LC-MS/MS methods.

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Section: Discussionsupporting

confidence: 63%

Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome

Caanen

Kuijper

Hompes

et al. 2016

European Journal of Endocrinology

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“…This 'transgenerational-effect' could be translated into humans as similar oxidative stress pattern was found in mothers with PCOS and their neonates, implying that mothers' deranged oxidative milieu could be transferred into the future metabolic vulnerability of their offspring (190).…”

Section: Role Of Lipo-oxidative Stressmentioning

confidence: 85%

The polycystic ovary syndrome: a position statement from the European Society of Endocrinology

Conway¹,

Dewailly²,

Diamanti-Kandarakis³

et al. 2014

European Journal of Endocrinology

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556

483

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Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS.

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“…In women with gestational DM, high levels of AGEs and advanced oxidation protein products (AOPPs) are also detectable in the umbilical blood of their neonates. Both, diabetic mother and neonate, showed higher AGE and AOPP levels compared with healthy controls (Boutzios et al 2013). Elevated AGE levels in women with gestational DM are associated with pregnancy complications such as birth asphyxia, congenital malformations, or stillbirth (Guosheng et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Accumulation of advanced glycation end products in the rabbit blastocyst under maternal diabetes

Haucke¹,

Simm²,

Henning³

et al. 2014

Reproduction

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Diabetes mellitus (DM) during pregnancy is one of the leading causes of perinatal morbidity and birth defects. The mechanism by which maternal hyperglycemia, the major teratogenic factor, induces embryonic malformations remains unclear. Advanced glycation end products (AGEs) are known to accumulate during the course of DM and contribute to the development of diabetic complications. Employing a diabetic rabbit model, we investigated the influence of maternal hyperglycemia during the preimplantation period on AGE formation (pentosidine, argpyrimidine, and N 3 -carboxymethyllysine (CML)) in the reproductive tract and the embryo itself. As a consequence of type 1 DM, the AGE levels in blood plasma increased up to 50%, correlating closely with an AGE accumulation in the endometrium of diabetic females. Embryos from diabetic mothers had increased protein-bound CML levels and showed enhanced fluorescent signals for AGE-specific fluorescence in the blastocyst cavity fluid (BCF). The quantification of CML by HPLC-mass spectrometry (MS/MS) showed a higher amount of soluble CML in the BCF of blastocysts from diabetic rabbits (0.26G0.05 mmol/l) compared with controls (0.18G0.02 mmol/l). The high amount of AGEs in blastocysts from diabetic mothers correlates positively with an increased AGER (receptor for AGE (RAGE)) mRNA expression. Our study gives alarming insights into the consequences of poorly controlled maternal diabetes for AGE formation in the embryo. Maternal hyperglycemia during the preimplantation period is correlated with an increase in AGE formation in the uterine environment and the embryo itself. This may influence the development of the embryo through increased AGE-mediated cellular stress by RAGEs.

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Polycystic ovary syndrome offspring display increased oxidative stress markers comparable to gestational diabetes offspring

Cited by 34 publications

References 66 publications

Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome

Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome

The polycystic ovary syndrome: a position statement from the European Society of Endocrinology

Accumulation of advanced glycation end products in the rabbit blastocyst under maternal diabetes

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