Vaspin, a novel adipokine in woman granulosa cells physiology and PCOS pathogenesis?

in Journal of Endocrinology
Authors:
Alice Bongrani UMR 85 Physiology of Reproduction and Behaviour, National Research Institute for Agriculture, Food and Environment (INRAE) Centre Val de Loire, Nouzilly, France

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Namya Mellouk UMR 85 Physiology of Reproduction and Behaviour, National Research Institute for Agriculture, Food and Environment (INRAE) Centre Val de Loire, Nouzilly, France

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Christelle Ramé UMR 85 Physiology of Reproduction and Behaviour, National Research Institute for Agriculture, Food and Environment (INRAE) Centre Val de Loire, Nouzilly, France

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Marion Cornuau Department of Reproductive Medicine and Biology, University Hospital of Tours, Tours, France

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Fabrice Guerif UMR 85 Physiology of Reproduction and Behaviour, National Research Institute for Agriculture, Food and Environment (INRAE) Centre Val de Loire, Nouzilly, France
Department of Reproductive Medicine and Biology, University Hospital of Tours, Tours, France

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Pascal Froment UMR 85 Physiology of Reproduction and Behaviour, National Research Institute for Agriculture, Food and Environment (INRAE) Centre Val de Loire, Nouzilly, France

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Joëlle Dupont UMR 85 Physiology of Reproduction and Behaviour, National Research Institute for Agriculture, Food and Environment (INRAE) Centre Val de Loire, Nouzilly, France

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Correspondence should be addressed to J Dupont: joelle.dupont@inra.fr
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Vaspin is a novel adipokine mainly expressed in visceral adipose tissue and closely related to obesity and insulin-resistance. Currently, data about its ovarian expression are limited to animal models and its role in human reproduction is largely unexplored. Our study’s aims were then to characterise vaspin expression in the human ovary and to study in vitro its effects on granulosa cells physiology. Secondly, we assessed vaspin and its receptor GRP78 variations in granulosa cells and follicular fluid of a cohort of 112 infertile women undergoing an in vitro fertilisation procedure and allocated to three groups, each including normal-weight and obese subjects: 34 PCOS patients, 33 women with isolated polycystic ovary morphology (ECHO group) and 45 controls. Vaspin and GRP78 expression in the ovary was assessed by immunohistochemistry, RT-qPCR and Western blot. Granulosa cells and follicular fluid were analysed by RT-qPCR and ELISA, respectively. In vitro, granulosa cells metabolism was studied after stimulation with recombinant human vaspin, with and without a siRNA directed against GRP78. Vaspin was highly expressed in the human ovary and concentration-dependently enhanced granulosa cells steroidogenesis, proliferation and viability through GRP78 (P < 0.0001). Vaspin levels in both granulosa cells and follicular fluid were significantly higher in obese women (P < 0.0001) and in the normal-weight ECHO group (P < 0.001), which also had the highest expression rates of GRP78 (P < 0.05). Although further investigation is needed, vaspin appears as a novel modulator of human granulosa cells physiology and possibly plays a role in PCOS pathogenesis, notably protecting from insulin-resistance induced complications.

Supplementary Materials

    • Supplementary Table 1 Simple regression analysis of vaspin follicular fluid (FF) concentration and mRNA levels in human luteinised granulosa cells (hlGC) with clinical/biological data and in vitro fertilisation procedure outcomes of study women
    • Supplementary Table 2 Simple linear regression analysis between GRP78 mRNA levels in granulosa cells (GC) and clinical/biological data and in vitro fertilisation procedure outcomes of study women
    • Supplementary Figure 1

 

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