Granulysin Produced by Uterine Natural Killer Cells Induces Apoptosis of Extravillous Trophoblasts in Spontaneous Abortion

Nakashima, Akitoshi; Shiozaki, Arihiro; Myojo, Subaru; Ito, Mika; Tatematsu, Mikiko; Sakai, Masatoshi; Takamori, Yasushi; Ogawa, Kazuyuki; Nagata, Kazuhiro; Saito, Shigeru

doi:10.2353/ajpath.2008.071169

Cited by 85 publications

(81 citation statements)

References 32 publications

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“…Yamada et al ( 2005 ) reported an increased proportion of perforin-positive uNK cells in decidua associated with sporadic miscarriage compared with controls. In contrast, Nakashima et al ( 2008 ) reported no difference in the proportion of uNK cells expressing perforin and granzyme B in sporadic miscarriage compared with controls, although the proportion of granulysin-positive uNK cells in decidua was increased and this was linked to an increase in EVT apoptosis.…”

Section: Miscarriagementioning

confidence: 73%

The Role of Uterine NK Cells in Normal Reproduction and Reproductive Disorders

Bulmer

Lash

2015

Advances in Experimental Medicine and Biology

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The human endometrium contains a substantial population of leucocytes which vary in distribution during the menstrual cycle and pregnancy. An unusual population of natural killer (NK) cells, termed uterine NK (uNK) cells, are the most abundant of these cells in early pregnancy. The increase in number of uNK cells in the mid-secretory phase of the cycle with further increases in early pregnancy has focused attention on the role of uNK cells in early pregnancy. Despite many studies, the in vivo role of these cells is uncertain. This chapter reviews current information regarding the role of uNK cells in healthy human pregnancy and evidence indicating their importance in various reproductive and pregnancy problems. Studies in humans are limited by the availability of suitable tissues and the limitations of extrapolation from animal models.

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Section: Miscarriagementioning

confidence: 73%

The Role of Uterine NK Cells in Normal Reproduction and Reproductive Disorders

Bulmer

Lash

2015

Advances in Experimental Medicine and Biology

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“…However, the question of whether cultured human dNK cells, which possess cytolytic machinery, are capable killers remains controversial. Some reports indicate that dNK cells kill cell targets [13,14], whereas others indicate that dNK cells fail to polarize granules to the target cell and, thus, are ineffective killers [15]. Currently, it is unknown whether human dNK cells are capable of inducing CTB apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Maternal Decidual Macrophages Inhibit NK Cell Killing of Invasive Cytotrophoblasts During Human Pregnancy

Gormley

Kapidzic

et al. 2013

Biology of Reproduction

114

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“…A recent study showed that accumulation of CD56 bright , granulysin-positive uNK cells in the decidua basalis was linked to pregnancy loss in humans [Nakashima et al 2008]. Interestingly, the numbers of CD56 bright , perforin-positive or granzyme B-positive uNK cells did not differ between spontaneously aborted and normal control samples, suggesting that constituents within uNK granules may be a better prognosticator for recurrent pregnancy loss than the magnitude of uNK cell numbers at the implantation site or the level of NK activity in the peripheral blood.…”

Section: Uterine Natural Killer Cellsmentioning

confidence: 99%

Embryonic Resorption and Polycyclic Aromatic Hydrocarbons: Putative Immune-mediated Mechanisms

Detmar

Jurisicova

2010

Systems Biology in Reproductive Medicine

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Polycyclic aromatic hydrocarbons (PAHs) are released into the environment as a result of incomplete fossil fuel combustion from industrial furnaces, woodburning stoves, and automobile exhaust fumes; however, the primary source of human exposure to these compounds is cigarette smoke. Embryonic and fetal loss after treatment with high doses of PAHs have been well documented in animal studies; however, few studies have addressed the reproductive consequences of long-term, low-level exposure to these chemicals. We previously reported that low doses of PAHs administered to ICR mice over a period of 9 weeks prior to conception resulted in early embryonic resorptions, whereby treated dams lost approximately 50% of their litter. During the course of these studies, we observed greater numbers of infiltrating uterine natural killer (uNK) cells into the placenta of PAH-exposed conceptuses. While exposure to high levels of PAHs has been shown to be immunosuppressive, increasing evidence suggests that chronic, low-dose exposure to PAHs may stimulate immune cells. Thus, we hypothesized that low-dose, chronic PAH exposure in our mouse model is mediating embryonic resorption by hyperstimulating maternal immune cells. In this review of the literature, we outline the rationale of our argument and present preliminary data, focussing upon PAH-mediated alterations in uNK cell dynamics and how these changes may be linked to early embryonic resorptions.

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Granulysin Produced by Uterine Natural Killer Cells Induces Apoptosis of Extravillous Trophoblasts in Spontaneous Abortion

Cited by 85 publications

References 32 publications

The Role of Uterine NK Cells in Normal Reproduction and Reproductive Disorders

The Role of Uterine NK Cells in Normal Reproduction and Reproductive Disorders

Maternal Decidual Macrophages Inhibit NK Cell Killing of Invasive Cytotrophoblasts During Human Pregnancy

Embryonic Resorption and Polycyclic Aromatic Hydrocarbons: Putative Immune-mediated Mechanisms

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