Age-related expression of TGF beta family receptors in human cumulus oophorus cells

J Assist Reprod Genet. 2017 Sep;34(9):1121-1129. doi: 10.1007/s10815-017-0930-6. Epub 2017 May 2.


Purpose: During ovarian follicle growth, local cellular interactions are essential for oocyte quality acquisition and successful fertilization. While cumulus cells (CCs) nurture oocytes, they also deliver oocyte-secreted factors (OSFs) that activate receptors on CCs. We hypothesized that disturbance of those interactions contributes to age-related lower reproductive success in women submitted to assisted reproductive technology treatments.

Methods: Women aged 27-48, without recognized personal reproductive disorder, were enrolled in the study and divided in <35- and ≥35-year-old groups. CCs collected upon follicle aspiration were processed for immunocytochemistry and RNA extraction. The expression patterns of OSF receptors BMPR2, ALK 4, ALK5, and activin receptor-like kinase (ALK6) were studied.

Results: Independently of age, receptors were found mostly in the cell periphery. The quantitative assay revealed that in older women, BMPR2, ALK 4, and ALK6 were all significantly decreased, whereas ALK5 was slightly increased.

Conclusions: Female age imparts an effect on the expression of OSF receptors in CCs. The findings indicate that reproductive aging affects the local regulation of signaling pathways mediated by BMPR2, ALK6, and ALK4 receptor activation, suggesting their joint involvement.

Keywords: Aging; Cumulus cells; Female infertility; Gene expression; Growth factors.

MeSH terms

  • Adult
  • Anaplastic Lymphoma Kinase
  • Bone Morphogenetic Protein Receptors, Type I / genetics
  • Bone Morphogenetic Protein Receptors, Type II / genetics
  • Cumulus Cells / metabolism*
  • Female
  • Fertilization in Vitro / methods
  • Gene Expression Regulation, Developmental / genetics
  • Humans
  • Middle Aged
  • Oocytes / growth & development
  • Oocytes / metabolism*
  • Ovarian Follicle / growth & development
  • Ovarian Follicle / metabolism*
  • Protein-Serine-Threonine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta / genetics
  • Reproductive Techniques, Assisted*


  • Receptors, Transforming Growth Factor beta
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases
  • BMPR2 protein, human
  • Bone Morphogenetic Protein Receptors, Type I
  • Bone Morphogenetic Protein Receptors, Type II
  • Receptor, Transforming Growth Factor-beta Type I
  • TGFBR1 protein, human