RETRACTED: Placental serotonin systems in pregnancy metabolic complications associated with maternal obesity and gestational diabetes mellitus

Murthi, Padma; Vaillancourt, Cathy

doi:10.1016/j.bbadis.2019.01.017

Cited by 19 publications

(23 citation statements)

References 117 publications

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“…Obesity before pregnancy presents a predisposition to gestational diabetes mellitus (GDM) [ 56 ]. GDM is one of the most common complications during pregnancy.…”

Section: Participation Of Aa Metabolites In Pregnancymentioning

confidence: 99%

“…GDM is defined as abnormal carbohydrate tolerance detected for the first time during pregnancy, which normalizes after birth [ 58 ]. Excessive body weight is characterized by an increase in the amount of proinflammatory oxylipids, which in turn leads to the formation of chronic inflammation state [ 56 ]. When compared to normal body weight patients, obese patients show a higher concentration of metabolites such as 5- and 15-HETE [ 59 ].…”

Section: Participation Of Aa Metabolites In Pregnancymentioning

confidence: 99%

“…GDM is also associated with placental hypersecretion of proinflammatory cytokines. In addition, high glucose levels can additionally stimulate proinflammatory cytokines, which affect normal placental development [ 56 ]. The syncytiotrophoblast layer is the primary barrier to maternofetal fatty acid transfer through the human placenta, and the fetus is dependent on syncytiotrophoblast-delivered fatty acids.…”

Section: Participation Of Aa Metabolites In Pregnancymentioning

confidence: 99%

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The Role of Arachidonic and Linoleic Acid Derivatives in Pathological Pregnancies and the Human Reproduction Process

Szczuko

Kikut

Komorniak

et al. 2020

IJMS

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The aim of the available literature review was to focus on the role of the proinflammatory mediators of AA and LA derivatives in pathological conditions related to reproduction and pregnancy. Arachidonic (AA) and linoleic acid (LA) derivatives play important roles in human fertility and the course of pathological pregnancies. Recent studies have demonstrated that uncontrolled inflammation has a significant impact on reproduction, spermatogenesis, endometriosis, polycystic ovary syndrome (PCOS) genesis, implantation, pregnancy and labor. In addition, cyclooxygenase-mediated prostaglandins and AA metabolite levels are higher in women’s ovarian tissue when suffering from PCOS. It has been demonstrated that abnormal cyclooxygenase-2 (COX-2) levels are associated with ovulation failure, infertility, and implantation disorders and the increase in 9-HODE/13-HODE was a feature recognized in PCOS patients. Maintaining inflammation without neutrophil participation allows pregnant women to tolerate the fetus, while excessive inflammatory activation may lead to miscarriages and other pathological complications in pregnancies. Additionally AA and LA derivatives play an important role in pregnancy pathologies, e.g., gestational diabetes mellitus, preeclampsia (PE), and fetal growth, among others. The pathogenesis of PE and other pathological states in pregnancy involving eicosanoids have not been fully identified. A significant expression of 15-LOX-1,2 was found in women with PE, leading to an increase in the synthesis of AA and LA derivatives, such as hydroxyeicozatetraenoic acids (HETE) and hydroxyoctadecadiene acids (HODE). Synthesis of the metabolites 5-, 8-, 12-, and 15-HETE increased in the placenta, while 20-HETE increased only in umbilical cord blood in women with preeclampsia compared to normal pregnancies. In obese women with gestational diabetes mellitus (GDM) an increase in epoxygenase products in the cytochrome P450 (CYP) and the level of 20-HETE associated with the occurrence of insulin resistance (IR) were found. In addition, 12- and 20-HETE levels were associated with arterial vasoconstriction and epoxyeicosatrienoic acids (EETs) with arterial vasodilatation and uterine relaxation. Furthermore, higher levels of 5- and 15-HETE were associated with premature labor. By analyzing the influence of free fatty acids (FFA) and their derivatives on male reproduction, it was found that an increase in the AA in semen reduces its amount and the ratio of omega-6 to omega-3 fatty acids showed higher values in infertile men compared to the fertile control group. There are several studies on the role of HETE/HODE in relation to male fertility. 15-Hydroperoxyeicosatetraenoic acid may affect the integrity of the membrane and sperm function. Moreover, the incubation of sperm with physiologically low levels of prostaglandins (PGE2/PGF2α) improves the functionality of human sperm. Undoubtedly, these problems are still insufficiently understood and require further research. However, HETE and HODE could serve as predictive and diagnostic biomarkers for pregnancy pathologies (especially in women with risk factors for overweight and obesity). Such knowledge may be helpful in finding new treatment strategies for infertility and the course of high-risk pregnancies.

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“…Obesity before pregnancy presents a predisposition to gestational diabetes mellitus (GDM) [ 56 ]. GDM is one of the most common complications during pregnancy.…”

Section: Participation Of Aa Metabolites In Pregnancymentioning

confidence: 99%

Section: Participation Of Aa Metabolites In Pregnancymentioning

confidence: 99%

Section: Participation Of Aa Metabolites In Pregnancymentioning

confidence: 99%

See 1 more Smart Citation

The Role of Arachidonic and Linoleic Acid Derivatives in Pathological Pregnancies and the Human Reproduction Process

Szczuko

Kikut

Komorniak

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…It has been suggested that inflammation in pregnant obese women or with GDM may influence fetal development [73]. Several lines of evidence from experimental animal models as well as from clinical studies indicate that maternal and placental inflammation associated with GDM and obesity can affect neurodevelopment and cause alterations in the inflammatory responses in their offspring [74,75]. The induction of GDM in a mouse model exacerbates the response of animals to experimentally induced maternal immune activation (MIA), with important consequences in brain development in the offspring.…”

Section: Inflammation Underlying Gdm Development and Derived Adverse mentioning

confidence: 99%

Molecular Modelling of Islet β-Cell Adaptation to Inflammation in Pregnancy and Gestational Diabetes Mellitus

Lorenzo

Martín-Montalvo

Vuilleumier

et al. 2019

IJMS

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Gestational diabetes mellitus (GDM), a metabolic disease that develops with the increase in insulin resistance during late pregnancy, is currently one of the most common complications affecting pregnancy. The polygenic nature of GDM, together with the interplay between different genetic variants with nutritional and environmental factors has hindered the full understanding of the etiology of this disease. However, an important genetic overlap has been found with type 2 diabetes mellitus (T2DM) and, as in the case of T2DM, most of the identified loci are associated with β-cell function. Early detection of GDM and adequate interventions to control the maternal glycemia are necessary to avoid the adverse outcomes for both the mother and the offspring. The in utero exposure to the diabetic milieu predispose these children for future diseases, among them T2DM, originating a vicious circle implicated in the increased prevalence of both GDM and T2DM. The involvement of inflammatory processes in the development of GDM highlights the importance of pancreatic β-cell factors able to favor the adaptation processes required during gestation, concomitantly with the protection of the islets from an inflammatory milieu. In this regard, two members of the Pax family of transcription factors, PAX4 and PAX8, together with the chromatin remodeler factor HMG20A, have gained great relevance due to their involvement in β-cell mass adaptation together with their anti-inflammatory properties. Mutations in these factors have been associated with GDM, highlighting these as novel candidates for genetic screening analysis in the identification of women at risk of developing GDM.

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“…Gestational diabetes mellitus (GDM), one of the most common metabolic complications of pregnancy, is characterized by aberrant placental functions, resulting in a significantly increased risk of developing Type 2 diabetes mellitus in both mother and child (Coustan, 2013;Dipla et al, 2017;Murthi & Vaillancourt, 2019).…”

Section: Introductionmentioning

confidence: 99%

SIRT3 deficiency is resistant to autophagy‐dependent ferroptosis by inhibiting the AMPK/mTOR pathway and promoting GPX4 levels

Han

Jiang

et al. 2020

Journal Cellular Physiology

154

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Ferroptosis, an autophagy‐dependent cell death, is characterized by lipid peroxidation and iron accumulation, closely associated with pathogenesis of gestational diabetes mellitus (GDM). Sirtuin 3 (SIRT3) has positive regulation on phosphorylation of activated protein kinase (AMPK), related to maintenance of cellular redox homeostasis. However, whether SIRT3 can confer autophagy by activating the AMPK‐mTOR pathway and consequently promote induction of ferroptosis is unknown. We used human trophoblastic cell line HTR8/SVneo and porcine trophoblastic cell line pTr2 to deterimine the mechanism of SIRT3 on autophagy and ferroptosis. The expression of SIRT3 protein was significantly elevated in trophoblastic cells exposed to high concentrations of glucose and ferroptosis‐inducing compounds. Increased SIRT3 expression contributed to classical ferroptotic events and autophagy activation, whereas SIRT3 silencing led to resistance against both ferroptosis and autophagy. In addition, autophagy inhibition impaired SIRT3‐enhanced ferroptosis. On the contrary, autophagy induction had a synergistic effect with SIRT3. Based on mechanistic investigations, SIRT3 depletion inhibited activation of the AMPK‐mTOR pathway and enhanced glutathione peroxidase 4 (GPX4) level, thereby suppressing autophagy and ferroptosis. Furthermore, depletion of AMPK blocked induction of ferroptosis in trophoblasts. We concluded that upregulated SIRT3‐enhanced autophagy activation by promoting AMPK‐mTOR pathway and decreasing GPX4 level to induce ferroptosis in trophoblastic cells. SIRT3 deficiency was resistant to high glucose‐ and erastin‐induced autophagy‐dependent ferroptosis and is, therefore, a potential therapeutic approach for treating GDM.

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RETRACTED: Placental serotonin systems in pregnancy metabolic complications associated with maternal obesity and gestational diabetes mellitus

Cited by 19 publications

References 117 publications

The Role of Arachidonic and Linoleic Acid Derivatives in Pathological Pregnancies and the Human Reproduction Process

The Role of Arachidonic and Linoleic Acid Derivatives in Pathological Pregnancies and the Human Reproduction Process

Molecular Modelling of Islet β-Cell Adaptation to Inflammation in Pregnancy and Gestational Diabetes Mellitus

SIRT3 deficiency is resistant to autophagy‐dependent ferroptosis by inhibiting the AMPK/mTOR pathway and promoting GPX4 levels

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