Ovarian kisspeptin expression is related to age and to monocyte chemoattractant protein-1

Merhi, Zaher; Thornton, Kim L.; Bonney, Elizabeth A.; Cipolla, Marilyn J.; Charron, Maureen J.; Büyük, Erkan

doi:10.1007/s10815-016-0672-x

Cited by 34 publications

(22 citation statements)

References 51 publications

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“…In the present study, GPR54 is expressed in human ECs, monocytes, macrophages, and VSMCs. Ovarian kiss1 and kiss1r expressions are increased in aged mice compared to reproductive‐age mice . Loss of function of GPR54 or KPs induces hypogonadotropic hypogonadism .…”

Section: Discussionmentioning

confidence: 99%

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Potent Vasoconstrictor Kisspeptin‐10 Induces Atherosclerotic Plaque Progression and Instability: Reversal by its Receptor GPR54 Antagonist

Sato

Shirai

Hontani

et al. 2017

JAHA

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BackgroundKisspeptin‐10 (KP‐10), a potent vasoconstrictor and inhibitor of angiogenesis, and its receptor, GPR54, have currently received much attention in relation to pre‐eclampsia. However, it still remains unknown whether KP‐10 could affect atherogenesis.Methods and ResultsWe evaluated the effects of KP‐10 on human umbilical vein endothelial cells, human monocyte‐derived macrophages, human aortic smooth muscle cells in vitro, and atherosclerotic lesions in apolipoprotein E–deficient (ApoE−/−) mice in vivo. KP‐10 significantly increased the adhesion of human monocytes to human umbilical vein endothelial cells, which was significantly inhibited by pretreatment with P234, a GPR54 antagonist. KP‐10 stimulated mRNA expression of tumor necrosis factor‐α, interleukin‐6, monocyte chemotactic protein‐1, intercellular adhesion molecule‐1, vascular adhesion molecule‐1, and E‐selectin in human umbilical vein endothelial cells. KP‐10 significantly enhanced oxidized low‐density lipoprotein–induced foam cell formation associated with upregulation of CD36 and acyl‐CoA:cholesterol acyltransferase‐1 in human monocyte‐derived macrophages. In human aortic smooth muscle cells, KP‐10 significantly suppressed angiotensin II–induced migration and proliferation, but enhanced apoptosis and activities of matrix metalloproteinase (MMP)‐2 and MMP‐9 by upregulation of extracellular signal‐regulated kinase 1 and 2, p38, Bcl‐2‐associated X protein, and caspase‐3. Four‐week‐infusion of KP‐10 into ApoE−/− mice significantly accelerated the development of aortic atherosclerotic lesions with increased monocyte/macrophage infiltration and vascular inflammation as well as decreased intraplaque vascular smooth muscle cells contents. Proatherosclerotic effects of endogenous and exogenous KP‐10 were completely canceled by P234 infusion in ApoE−/− mice.ConclusionsOur results suggest that KP‐10 may contribute to accelerate the progression and instability of atheromatous plaques, leading to plaque rupture. The GPR54 antagonist may be useful for prevention and treatment of atherosclerosis. Thus, the KP‐10/GPR54 system may serve as a novel therapeutic target for atherosclerotic diseases.

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Section: Discussionmentioning

confidence: 99%

“…Ovarian kiss1 and kiss1r expressions are increased in aged mice compared to reproductiveage mice. 27 Loss of function of GPR54 or KPs induces hypogonadotropic hypogonadism. 26,28,29 Bowe et al have shown that KPs stimulate the release of insulin from the pancreas.…”

Section: Discussionmentioning

confidence: 99%

Potent Vasoconstrictor Kisspeptin‐10 Induces Atherosclerotic Plaque Progression and Instability: Reversal by its Receptor GPR54 Antagonist

Sato

Shirai

Hontani

et al. 2017

JAHA

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“…Along the same lines, a very recent study confirmed our results demonstrating that ovarian mRNA levels of Kiss1 and its receptor Kiss1R increase in aged mice compared to that in younger mice. Although the authors failed to measure ovarian kisspeptin mRNA in women GCs, they found that ovarian Kiss1R mRNA levels increase according to age (Merhi et al 2016). Interestingly, ovarian KP has a positive correlation with ovarian NE release during the subfertile period in the rat (Fernandois et al 2016).…”

Section: Role Of Ovarian Kisspeptin In Ovarian Ageing and Its Relatiomentioning

confidence: 99%

Ovarian function and reproductive senescence in the rat: role of ovarian sympathetic innervation

2017

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Successful reproduction is the result of a myriad interactions in which the ovary and the ovarian follicular reserve play a fundamental role. At present, women who delay maternity until after 30 years of age have a decreased fertility rate due to various causes, including damaged follicles and a reduction in the reserve pool of follicles. Therefore, the period just prior to menopause, also known as the subfertile period, is important. The possibility of modulating the follicular pool and the health of follicles during this period to improve fertility is worth exploring. We have developed an animal model to study the ovarian ageing process during this subfertile period to understand the mechanisms responsible for reproductive senescence. In the rat model, we have shown that the sympathetic nervous system participates in regulating the follicular development during ovarian ageing. This article reviews the existing evidence on the presence and functional role of sympathetic nerve activity in regulating the follicular development during ovarian ageing, with a focus on the subfertile period. Free Spanish abstract: A Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/153/2/ R59/suppl/DC1. Reproduction (2017) 153 R59-R68

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“…Kisspeptin has been shown to affect ovarian follicular development and ovarian reserve. We have demonstrated that older mice had significantly higher Kiss1 and Kiss1r levels in their ovaries compared with younger mice (39). The sensitivity of kisspeptin may be altered by age-related upregulation of Kiss1r (39).…”

Section: Discussionmentioning

confidence: 73%

Role of adiponectin in ovarian follicular development and ovarian reserve

et al. 2019

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Adiponectin levels are associated with anti-Müllerian hormone (AMH) and kisspeptin levels in non-ovarian tissues. The objective of the present study was to investigate the association between adiponectin and the genes important for ovarian follicular development and ovarian reserve, specifically AMH and kisspeptin, and their corresponding receptors. In the first experiment, the mRNA levels of anti-Müllerian hormone (amh) and its receptor (Amhr2), as well as those of kisspeptin (Kiss1) and its receptor (Kiss1r), were quantified by reverse transcription-polymerase chain reaction analysis in the ovaries of two groups of mice [adiponectin-knockout (KO) vs. control] that underwent oophorectomy. The second experiment measured follicular phase serum AMH and follicular fluid adiponectin levels in 25 women who underwent controlled ovarian hyperstimulation for in vitro fertilization. Compared with the control mice, adiponectin-KO mice had 6.5 times lower Kiss1 mRNA levels (P= 0.009) and a tendency for lower ovarian Kiss1r mRNA expression levels (P= 0.06). However, adiponectin-KO mice had significantly higher Amhr2 mRNA levels (P=0.01). In all women participants, there was a positive correlation between serum AMH and follicular fluid adiponectin concentrations (r=0.54, P=0.006). The findings of the present study indicate that adiponectin may play a role in ovarian physiology through its impact on genes crucial for ovarian follicular development and ovarian reserve, such as kisspeptin and AMH. Understanding the role of adiponectin in ovarian function may improve our knowledge of the pathophysiology underlying ovulatory dysfunction in obese women, who usually have low adiponectin levels, and overcome reproductive barriers.

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Ovarian kisspeptin expression is related to age and to monocyte chemoattractant protein-1

Cited by 34 publications

References 51 publications

Potent Vasoconstrictor Kisspeptin‐10 Induces Atherosclerotic Plaque Progression and Instability: Reversal by its Receptor GPR54 Antagonist

Potent Vasoconstrictor Kisspeptin‐10 Induces Atherosclerotic Plaque Progression and Instability: Reversal by its Receptor GPR54 Antagonist

Ovarian function and reproductive senescence in the rat: role of ovarian sympathetic innervation

Role of adiponectin in ovarian follicular development and ovarian reserve

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