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Effects of adipocyte-secreted factors on decidualized endometrial cells: modulation of endometrial receptivity in vitro

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Abstract

Obesity is defined as an excessive accumulation of adipose tissue that may lead to health complications. Mounting evidence indicates that obesity has a negative impact on fertility. Yet, the link between adipose tissue biology and infertility remains unclear. We aimed to investigate the communication between the adipose tissue and the reproductive system and the importance of this cross talk for the development of a receptive endometrium. To that end, we generated an in vitro model with endometrial and adipocyte cell lines. Sexual hormones, progesterone and estradiol, were used to decidualize endometrial cells and sensitize adipocytes. Decidualization produced a simultaneous increase of adipokine receptors in endometrial cells paralleling changes in their receptivity status. Furthermore, sensitization of 3T3-L1 adipocytes increased mRNA levels of leptin and resistin and decreased the expression of adiponectin and chemerin levels. This was accompanied by increased isoproterenol-induced lipolysis and reduced insulin-stimulated glucose uptake. Lastly, conditioned culture medium of those sensitized adipocytes was used to feed endometrial cells. This treatment resulted in (i) upregulation of genes previously identified as positive regulators of endometrial receptivity, such as leukemia inhibitory factor and glutathione peroxidase 3, and (ii) downregulation of interleukin-15 and mucin1, both genes negatively related with endometrial receptivity. Our results indicate that the endocrine communication between adipose tissue and the reproductive system is bidirectional and stress the importance of the adipose tissue to modulate the reproductive fitness.

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Acknowledgments

We are grateful to Mª Pilar García-Sobreviela for her invaluable technical assistance. J.M.A-M is supported by the Miguel Servet program from the Instituto de Salud Carlos III (Spain) and by the Marie-Curie Action: 303717-APOMET from the European Commission. S.G-S. is partially supported by a predoctoral fellowship from the Diputación General de Aragón (Spain).

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Authors and Affiliations

  1. Adipocyte and Fat Biology Laboratory (AdipoFat), Unidad de Investigación Traslacional, Instituto Aragonés de Ciencias de la Salud (IACS), Hospital Universitario Miguel Servet, Zaragoza, Spain

    Silvia Gamundi-Segura, Jose A. Horcajadas & Jose M. Arbones-Mainar

  2. Instituto Valenciano de Infertilidad (IVI) Zaragoza, Zaragoza, Spain

    Jose Serna

  3. Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA, USA

    Sergio Oehninger

  4. Universidad Pablo de Olavide, Seville, Spain

    Jose A. Horcajadas

  5. CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto Salud Carlos III, Madrid, Spain

    Jose M. Arbones-Mainar

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  1. Silvia Gamundi-Segura
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  2. Jose Serna
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  4. Jose A. Horcajadas
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  5. Jose M. Arbones-Mainar
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Correspondence to Jose M. Arbones-Mainar.

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Gamundi-Segura, S., Serna, J., Oehninger, S. et al. Effects of adipocyte-secreted factors on decidualized endometrial cells: modulation of endometrial receptivity in vitro. J Physiol Biochem 71, 537–546 (2015). https://doi.org/10.1007/s13105-015-0393-0

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  • DOI: https://doi.org/10.1007/s13105-015-0393-0

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