Are leptin and adiponectin involved in recurrent pregnancy loss?

Sérazin, Valérie; Duval, Fabien; Wainer, R.; Ravel, Célia; Vialard, François; Molina-Gomès, Denise; Dieudonné, Marie‐Noëlle; Santos, Esther Dos

doi:10.1111/jog.13623

Cited by 13 publications

(19 citation statements)

References 52 publications

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“…Surprisingly, it has pro-inflammatory function inducing the release of pro-inflammatory cytokines (such as TNF-α, IL-6, IL-1β) and prostaglandins (such as PG 2α ) in the placenta, by regulating NF-κB and PPAR-γ signaling pathway [59], in an attempt for an essential degree of inflammation necessary to promote syncytialization and the invasive capacity of cytotrophoblast. Adiponectin to leptin ratio is diminished in PCOS [60] and is elevated in those diagnosed with RPL only [61]. Our data showed significantly lower adiponectin levels in the PCOS group and subgroups, when compared to controls, coinciding with the aforementioned.…”

Section: Plos Onesupporting

confidence: 75%

“…Furthermore, homocysteine is a potent inhibitor of adipogenesis, stimulating AMPK and suppressing PPAR-γ signaling pathways; and it intensifies the effect of hyperandrogenism on cardiovascular risk in females diagnosed with PCOS [61]. PCOS group and subgroups had higher homocysteine levels when compared to control, having a direct association with insulin resistance [62].…”

Section: Plos Onementioning

confidence: 99%

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Circulating levels of Meteorin-like protein in polycystic ovary syndrome: A case-control study

et al. 2020

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Patients diagnosed with polycystic ovary syndrome (PCOS) are at high risk of developing a myriad of endocrinologic and metabolic derailments. Moreover, PCOS is a leading cause of habitual abortion, also known as recurrent pregnancy loss (RPL). Meteorin-like protein (Metrnl) is a newly discovered adipokine with the potential to counteract the metaflammation. This study aimed at determining the associations of serum Metrnl levels with homocysteine, hs-CRP, and some components of metabolic syndrome in PCOS-RPL and infertile PCOS patients.This case-control study was conducted in 120 PCOS patients (60 PCOS-RPL and 60 infertile) and 60 control. Serum hs-CRP and homocysteine were assessed using commercial kits, while adiponectin, Metrnl, FSH, LH, free testosterone and insulin levels were analyzed using ELISA technique. Serum Metrnl levels were found to be lower in PCOS patients when compared to controls (67.98 ± 26.66 vs. 96.47 ± 28.72 pg/mL, P <0.001)). Furthermore, serum adiponectin levels were lower, while free testosterone, fasting insulin, HOMA-IR, homocysteine, and hs-CRP were significantly higher in PCOS group compared to controls. Moreover, serum Metrnl correlated with BMI, adiponectin, and homocysteine in controls, and inversely correlated with FBG, fasting insulin, and HOMA-IR in PCOS group and subgroups. Besides, it inversely correlated with hs-CRP in control, and PCOS group and subgroups. These findings revealed a possible role of Metrnl in the pathogenesis of PCOS and RPL. Nevertheless, there is a necessity for future studies to prove this concept.

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Section: Plos Onesupporting

confidence: 75%

Section: Plos Onementioning

confidence: 99%

Circulating levels of Meteorin-like protein in polycystic ovary syndrome: A case-control study

et al. 2020

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“…Therefore, activation of AMPK can reverse the adverse pregnancy outcome caused by insulin resistance through the interaction between AMPK and the PI3K/Akt signaling pathway [28]. However, the researchers also had some inconsistent results; some researchers shown that plasma APN levels are significantly higher in women with recurrent abortions [29]. This finding may be related to the proinflammatory role of APN in human placental tissue, as APN stimulates the production of proinflammatory cytokines and prostaglandins through trophoblast cells and inhibits the supply of placental glucose and amino acids to play a pro-apoptotic role [28].…”

Section: Discussionmentioning

confidence: 99%

“… Adiponectin and its mechanism: Adiponectin (APN) is a protein of 244 amino acid residues encoded by apM1 gene and secreted specifically by fat cells. It is an important messenger for fat tissues to communicate with other organs [ 29 , 35 ]. APN receptor genes (AdipoR1 and AdipoR2) are highly expressed in the secretory stage of the female endometrium, and the mRNA levels of APN, AdipoR1, and AdipoR2 are significantly increased in implantation, suggesting that APN is involved in the changes of the endometrium before implantation [ 36 ].…”

Section: Appendixmentioning

confidence: 99%

Adiponectin Reduces Embryonic Loss Rate and Ameliorates Trophoblast Apoptosis in Early Pregnancy of Mice with Polycystic Ovary Syndrome by Affecting the AMPK/PI3K/Akt/FoxO3a Signaling Pathway

et al. 2020

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Reports in recent years have suggested that adiponectin (APN) improves insulin resistance and inhibits apoptosis by activating the AMP-activated protein kinase (AMPK) pathway and the PI3K/Akt signaling pathway after binding to its receptor. This study aims to explore the mechanism by which APN reduces embryo loss rate and trophoblast apoptosis in early pregnancy of mice with polycystic ovary syndrome (PCOS). PCOS mice were subcutaneously injected with APN (10 μg mg kg−1 day−1) on 11 consecutive days from the 3rd day of pregnancy onwards to observe the change of the embryo loss rate of PCOS mice induced by APN. Quantitative real-time PCR and Western blot were used to determine the relative expressions of mRNA and the proteins AMPK, PI3K, and Akt in mouse uterine tissue. At the same time, primary cultured mouse villous trophoblast cells were used to further explore the underlying mechanisms in vitro. APN significantly reduces the pregnancy loss rate of PCOS mice. At the same time, APN increases phosphorylation and mRNA expression levels of AMPK, PI3K, and Akt in PCOS mouse uterine tissue. In addition, trophoblast cells of model mice were treated with APN and inhibitors, and APN was found to reduce trophoblast cell apoptosis by affecting the phosphorylation levels of AMPK, PI3K, Akt, and FoxO3a proteins. APN reduces the embryo loss rate and ameliorates trophoblast apoptosis in PCOS mice by affecting the AMPK/PI3K/AKT/FoxO3a signaling pathway.

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“…Simultaneously, adipocytes release deranged concentrations of adipokines that further aggravate insulin resistance, enhance inflammatory responses, and may negatively affect endocrine and reproductive systems . Adiponectin is an adipokine that positively regulates insulin sensitivity, and protects against obesity‐ and pregnancy‐associated complications—including RPL . Adiponectin levels are lower in females diagnosed with PCOS than their normal counterparts .…”

Section: Introductionmentioning

confidence: 99%

Circulating levels of C1q/TNF‐α‐related protein 6 (CTRP6) in polycystic ovary syndrome

et al. 2020

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Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting females of reproductive age. It has been associated with cardiometabolic disorders including diabetes mellitus and cardiovascular disorders, and increases the risk of developing fecundity pathologies including recurrent pregnancy loss (RPL) and infertility. C1q/tumor necrosis factor‐α‐related protein‐6 (CTRP6) is a novel adipokine involved in glucose and lipid metabolism, host inflammation, and organogenesis. In the present study, we aimed to determine the association of serum CTRP6 levels with some components of metabolic syndrome in PCOS patients (infertile PCOS [inf‐PCOS] and PCOS‐RPL). This case–control study included 120 PCOS patients (60 inf‐PCOS and 60 PCOS‐RPL) and 60 healthy controls. Serum high‐sensitivity C‐reactive protein (hs‐CRP) and homocysteine were measured using commercial kits, while adiponectin and CTRP6 levels were assessed using ELISA technique. Inf‐PCOS and PCOS‐RPL individuals had higher levels of serum CTRP6 than controls (546.15 ± 125.02 ng/ml and 534.04 ± 144.19 ng/ml vs. 440.16 ± 159.24 ng/ml; both p < .001). Moreover, serum adiponectin levels were significantly reduced, while fasting insulin, homeostasis model assessment of insulin resistance, free testosterone, and hs‐CRP levels were significantly elevated in PCOS group, when compared with controls. Furthermore, serum CTRP6 positively associated with body mass index in all subjects. It showed an inverse correlation with adiponectin in PCOS group and subgroups. However, it had a direct association with hs‐CRP in PCOS group and inf‐PCOS subgroup, but not PCOS‐RPL subgroup. These findings unravel a probable role of CTRP6 in PCOS pathogenesis, which poses a possibility to be a good diagnostic target. However, further investigation is needed.

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Are leptin and adiponectin involved in recurrent pregnancy loss?

Abstract: This study demonstrates that adiponectinemia is increased in patients suffering from RPL. However, association of adiponectin with adverse pregnancy outcomes remains to be elucidated.

Cited by 13 publications

References 52 publications

Circulating levels of Meteorin-like protein in polycystic ovary syndrome: A case-control study

Circulating levels of Meteorin-like protein in polycystic ovary syndrome: A case-control study

Adiponectin Reduces Embryonic Loss Rate and Ameliorates Trophoblast Apoptosis in Early Pregnancy of Mice with Polycystic Ovary Syndrome by Affecting the AMPK/PI3K/Akt/FoxO3a Signaling Pathway

Circulating levels of C1q/TNF‐α‐related protein 6 (CTRP6) in polycystic ovary syndrome

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