4.5 Article

Effect of theIDOGene on Pregnancy in Mice with Recurrent Pregnancy Loss

Journal

REPRODUCTIVE SCIENCES
Volume 28, Issue 1, Pages 52-59

Publisher

SPRINGER HEIDELBERG
DOI: 10.1007/s43032-020-00264-w

Keywords

Mice; Recurrent spontaneous abortion; Maternal-fetal interface; Indoleamine 2; 3-dioxygenase; Regulatory T cells

Funding

  1. Guizhou Provincial Natural Science Foundation [(2015)7436]
  2. National Natural Science Foundation of China [81460242]

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The study showed that the IDO gene can reduce embryo absorption rate and improve pregnancy outcome in an RPL mouse model by upregulating Tregs and reducing inflammatory response.
The aim of this study is to investigate the effect of theIDO(indoleamine 2,3-dioxygenase) gene on pregnancy outcome in mice with recurrent pregnancy loss (RPL) and its mechanism of action in the maternal-fetal interface. An RPL model was established via natural mating of female CBA/J mice with male DBA/2 mice; thereafter, the female mice were randomly divided into groups treated with LV-EGFP (enhanced green fluorescent protein)-IDO (lentivirus vector carrying IDO-EGFP gene), LV-EGFP (negative control lentivirus vector), or phosphate-buffered saline (control). The mice were sacrificed at 13.5 days of pregnancy, and the embryo absorption rate was determined. Peripheral blood regulatory T cells (Tregs) from the pregnant mice were detected using flow cytometry. Placental and decidual tissue IDO expression was detected using immunofluorescence and Western blotting. Inflammatory cell infiltration of the placental and decidual tissue was observed using hematoxylin-eosin (HE) staining. The LV-EGFP-IDO group had a significantly lower embryo absorption rate than the LV-EGFP and control groups (P = 0.0006 andP = 0.0049, respectively) and significantly more Tregs than the LV-EGFP and control groups (P = 0.0151 andP = 0.0392, respectively). Placental and decidual IDO protein levels correlated positively with peripheral blood Treg expression levels. The LV-EGFP-IDO group had significantly higher placental and decidual IDO protein levels than the LV-EGFP and control groups (P< 0.005), and it had significantly less inflammatory cell infiltration than the LV-EGFP and control groups. TheIDOgene may reduce the embryo absorption rate in an RPL mouse model, possibly improving pregnancy outcome by upregulating Tregs and reducing the inflammatory response.

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