Obstet Gynecol Sci.  2019 Jul;62(4):212-223. 10.5468/ogs.2019.62.4.212.

Pathogenetic factors involved in recurrent pregnancy loss from multiple aspects

• Pei CZ
• Kim YJ
• Baek KH

• KMID: 2451650
• DOI: http://doi.org/10.5468/ogs.2019.62.4.212

Abstract

Recurrent pregnancy loss (RPL) is a common complication in obstetrics, affecting about 5% of women of childbearing age. An increase in the number of abortions results in escalation in the risk of miscarriage. Although concentrated research has identified numerous causes for RPL, about 50% of them remain unexplained. Pregnancy is a complex process, comprising fertilization, implantation, organ and tissue differentiation, and fetal growth, which is effectively controlled by a number of both maternal and fetal factors. An example is the immune response, in which T cells and natural killer cells participate, and inflammation mediated by tumor necrosis factor or colony-stimulating factor, which hinders embryo implantation. Furthermore, vitamin D affects glucose metabolism and inhibits embryonic development, whereas microRNA has a negative effect on the gene expression of embryo implantation and development. This review examines the causes of RPL from multiple perspectives, and focuses on the numerous factors that may result in RPL.

Keyword

Proteomics; Recurrent miscarriage; Vitamin D

MeSH Terms

Abortion, Habitual
Abortion, Spontaneous
Colony-Stimulating Factors
Embryo Implantation
Embryonic Development
Female
Fertilization
Fetal Development
Gene Expression
Glucose
Humans
Inflammation
Killer Cells, Natural
Metabolism
MicroRNAs
Obstetrics
Pregnancy*
Proteomics
T-Lymphocytes
Tumor Necrosis Factor-alpha
Vitamin D
Colony-Stimulating Factors
Glucose
MicroRNAs
Tumor Necrosis Factor-alpha
Vitamin D

Figure

• 

  Fig. 1 Role of natural killer (NK) cells in creating a supporting environment for embryo implantation. T cell immunoglobulin (type I membrane protein) and mucin-containing protein 3+ uterine NK cells combine with ligand galectin-9 (Gal-9) to secrete interleukin (IL)-4, transforming growth factor (TGF)-β, IL-10, with decreased production of tumor necrosis factor (TNF)-α, thereby inducing immune suppression and tolerance, and creating an environment conducive to embryo implantation.

• 

  Fig. 2 Effect of activated vitamin D on immune cells. Activated vitamin D stimulates T helper (Th)2 cells to secrete anti-inflammatory factors, promotes T-reg cell differentiation and proliferation, and increases the number of CD8+ cells. Activated vitamin D stimulates Th1 cells and Th17 cells to secrete pro-inflammatory factors, and increase the function/number of CD4+ cells. TNF, tumor necrosis factor; IFN, interferon; IL, interleukin.

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