miR-133b Reverses the Hydrosalpinx-induced Impairment of Embryo Attachment Through Down-regulation of SGK1

J Clin Endocrinol Metab. 2016 Apr;101(4):1478-89. doi: 10.1210/jc.2015-1588. Epub 2016 Feb 3.

Abstract

Context: Hydrosalpinx impairs endometrial receptivity and embryo implantation. However, the exact underlying mechanism remains elusive.

Objective: This study aimed to explore how an miR-133b-mediated mechanism controls endometrial receptivity and embryo attachment in the endometrium of women with hydrosalpinx.

Design, setting, patients, and interventions: Ishikawa cells were treated with hydrosalpinx fluid (HF) from infertile patients and cultured for in vitro analysis. The attachment rates of BeWo spheroids and mouse embryos to Ishikawa cells were assayed.

Primary outcome measure: miR-133b, serum and glucocorticoid-regulated kinase 1 (SGK1), and homeobox A10 (HOXA10) expression levels were evaluated by quantitative real-time PCR and Western blot assays.

Results: The expression of miR-133b and HOXA10 was significantly down-regulated, whereas the miR-133b target gene SGK1 was up-regulated in mid-secretory endometrial tissues of women with hydrosalpinx and in HF-treated Ishikawa cells. Moreover, hydrosalpinx inhibited miR-133b expression through the activation of nuclear factor κB/p65, and SGK1 decreased miR-133b-induced HOXA10 expression by phosphorylating cAMP responsive element binding protein in Ishikawa cells. Our results also showed that miR-133b and HOXA10 contributed to BeWo spheroid adhesiveness, whereas SGK1 inhibited BeWo spheroid attachment to Ishikawa cells. Importantly, miR-133b overexpression reversed the HF-mediated impairment of embryo attachment in vitro.

Conclusions: miR-133b directly targets SGK1 to reverse the hydrosalpinx-induced down-regulation of HOXA10 and to attenuate the impairment of embryo attachment in vitro.

MeSH terms

  • Adult
  • Blotting, Western
  • Cells, Cultured
  • Embryo Implantation / genetics*
  • Fallopian Tube Diseases / physiopathology*
  • Female
  • Homeobox A10 Proteins
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Immediate-Early Proteins / antagonists & inhibitors
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism*
  • Infertility, Female / etiology
  • Infertility, Female / pathology
  • Infertility, Female / prevention & control*
  • MicroRNAs / genetics*
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Real-Time Polymerase Chain Reaction

Substances

  • Homeobox A10 Proteins
  • Homeodomain Proteins
  • Immediate-Early Proteins
  • MIRN133 microRNA, human
  • MicroRNAs
  • HOXA10 protein, human
  • Protein Serine-Threonine Kinases
  • serum-glucocorticoid regulated kinase