Functional expression of the free fatty acids receptor-1 and -4 (FFA1/GPR40 and FFA4/GPR120) in bovine endometrial cells

  • Pamela Valenzuela
  • Stefanie Teuber
  • Carolina Manosalva
  • Pablo Alarcón
  • Carlos D. Figueroa
  • Marcelo Ratto
  • Rafael A. Burgos
  • Maria A. HidalgoEmail author
Original Article


Endometrial epithelial cells play a key defensive role as part of the innate immune response of cow uterus. An association between risk of acquiring infectious diseases and increased levels of free fatty acids postpartum has been suggested, and the use of omega-3 fatty acids such as docosahexaenoic acid (DHA) has been proposed as a beneficial strategy to improve immunity and fertility. The goal of our study was to demonstrate the presence of free fatty acid (FFA)-1 and 4 receptors in endometrial cells and to investigate their role on DHA interference in lipopolysaccharide (LPS)-induced inflammatory endometrial activation. We demonstrated that the bovine endometrial (BEND) cells line and bovine endometrium express both FFA1 and FFA4 receptors. FFA1 and FFA4 receptors were localized in the epithelium lining the endometrial cavity and in endometrial glands whereas in BEND cells a characteristic cell membrane localization of both receptors was observed. DHA, a FFA4 natural agonist, increased intracellular calcium mobilization in BEND cells, but the FFA1 agonists oleic and linoleic acids did not increase this response. DHA-induced intracellular calcium mobilization was inhibited by the FFA4 and FFA1 antagonists AH7614 and GW1100, respectively. DHA significantly reduced LPS-induced prostaglandin E2 (PGE2) production, but none of the antagonists reduced the effect produced by DHA. On the contrary, linoleic acid increased LPS-induced PGE2 production. In conclusion, endometrial cells express FFA4 and FFA1 receptors, and DHA induces intracellular calcium release via FFA4 and FFA1 receptors. DHA reduces PGE2, but this response was not mediated by FFA4 or FFA1 receptors.


Fatty acids receptor BEND cells DHA Prostaglandin E2 Cows 


Author’s contribution

P. Valenzuela, S. Teuber and C. Manosalva performed the experiments; P. Alarcon, C. D. Figueroa and M. A. Hidalgo analyzed the results; M. Ratto, R. A. Burgos and M. A. Hidalgo designed the research; C. D. Figueroa, R. A. Burgos and M. A. Hidalgo wrote the paper.


This study was funded by Grants Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT) 1151047 and DID-UACh 2014–23. PV was supported by a Scholarship (21140149) funded by Comisión Nacional de Investigación Científica y Tecnológica (CONICYT).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with animals performed by any of the authors.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Laboratory of Molecular Pharmacology, Institute of Pharmacology, Faculty of Veterinary ScienceUniversidad Austral de ChileValdiviaChile
  2. 2.Institute of Pharmacy, Faculty of SciencesUniversidad Austral de ChileValdiviaChile
  3. 3.Institute of Anatomy, Histology and Pathology, Faculty of MedicineUniversidad Austral de ChileValdiviaChile
  4. 4.Institute of Animal Science, Faculty of Veterinary ScienceUniversidad Austral de ChileValdiviaChile

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