Specific Natural Killer Cells Promote Fetal Growth During Pregnancy

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Highlights:

• The growth factors pleiotrophin and osteoglycin secreted by the natural killer cells in the uterine lining promote the fetal development in the early months of pregnancy
• A reduction in the natural killer cells has been associated with spontaneous abortions and fetal growth retardation
• Replacement of the cells in animal studies has been able to reverse the growth retardation

A subset of natural killer cells in the uterus secretes growth factors that nourish the fetus and promote its growth in the early stages of pregnancy. Their function is quite unlike that of the usual natural killer cells that fight against infection and tumor formation. This study was published in Immunity.

Previous studies have demonstrated that natural killer cells are noted in large numbers in the uterus during the early stages of pregnancy but decline considerably once the placenta is formed after four months into the pregnancy. Scientists now found that:

• A specific type of natural killer cells in the uterus called the CD49a+Eomes+ subset secretes growth-promoting factors called pleiotrophin and osteoglycin, which support the development of the fetus. Pleiotrophin may be involved in blood vessel proliferation and the development of the brain, bone and cartilage, while osteoglycin takes part in the development of the heart, skin and eyes. Thus, both these factors are extremely crucial for fetal growth.
• The secretion of the growth factors is induced by the HLA-G molecules on the natural killer cells. The production of growth factors was less from the fetal tissue that has undergone miscarriage.
• Pregnancies at an older age in mice was associated with reduced production of growth factors, which could explain the growth retardations and developmental delays normally associated with these pregnancies. Several mechanisms have been suggested that could contribute to a reduction in the growth factors which may include intrinsically programmed events in the natural killer cells, genetic changes that may be influenced by reactive oxygen species, a decline in the uterine microenvironment or the production of pro-inflammatory mediators.
• A reduced number of the natural killer cells in pregnant mice resulted in severe fetal growth restriction and defective development of the fetal skeletal system.
• When such cells are transferred into pregnant mice with impaired fetal growth, the impairment of fetal growth could be reversed.

These findings thus suggest that insufficient secretion of growth-promoting factors by a specific subset of natural killer cells may be responsible for restricted fetal development in humans. Restoration of these cells either through an intravenous infusion or through a vaginal pessary could be used to restore fetal growth, and ensure the birth of a normal baby.

‘Uterine natural killer cells secrete the growth factors pleiotrophin and osteoglycin that promote fetal growth and prevent retardation in the early months of pregnancy.’

The results of the study provide hope for treating conditions like fetal growth restriction, recurrent spontaneous abortion due to unknown cases and age-related fetal loss. The use of a specific type of natural killer cells instead of pluripotent cells is much less likely to induce the formation of a tumor. The natural killer cells can be produced from cells obtained from the mother's uterus or from another woman, or from the umbilical cord.

The exact mechanism through which the growth factors secreted by the natural killer cells promote fetal growth is not clear but it could be that they directly cross over from the mother to the fetus, or indirectly promote the growth of the placenta and blood vessels, thereby improving the nourishment to the fetus.

About Natural Killer Cells

Natural killer cells are a type of white blood cells that fight against viral infections and tumor formation. During pregnancy, they promote the growth of blood vessels, improve birth weight and fetal growth. They have been used in the treatment of cancer.

Reference:

1. Fu, B., Zhou, Y., and Ni, X., et al. "Natural Killer Cells Promote Fetal Development through the Secretion of Growth-Promoting Factors." Immunity DOI: http://dx.doi.org/10.1016/j.immuni.2017.11.018

Source: Medindia

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