Uterine natural killer (uNK) cells and their missions during pregnancy: A review

Acar, Nuray; Üstünel, İ̇smail; Demir, Ramazan

doi:10.1016/j.acthis.2009.12.001

Cited by 40 publications

(30 citation statements)

References 152 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Decidual stromal cells produce many products that inhibit the activity of invasive fetal proteins (30,31), and they produce molecules that signal to uNK cells, which are known to regulate placental invasion in humans among other functions (9)(10)(11)(12). Prolactin is one such product of decidual cells: it has been shown to increase proliferation of uNK cells and increase their cytotoxicity in vitro (6)(7)(8).…”

Section: Discussionmentioning

confidence: 99%

“…The precise functions of decidual prolactin remain unclear, but in vitro it is known to cause the proliferation of and enhance the cytotoxicity of uterine natural killer (uNK) cells (6)(7)(8), immune cells that regulate fetal invasion into maternal tissues (9)(10)(11)(12). Prolactin protein concentrations from human decidua are much higher than those from rhesus monkeys, and human decidual tissue from early in pregnancy has a much higher capacity to release prolactin in vitro (13,14).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Transformation of a transposon into a derived prolactin promoter with function during human pregnancy

Emera

Wagner

2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Transposable elements (TEs) are known to provide DNA for host regulatory functions, but the mechanisms underlying the transformation of TEs into cis-regulatory elements are unclear. In humans two TEs-MER20 and MER39-contribute the enhancer/ promoter for decidual prolactin (dPRL), which is dramatically induced during pregnancy. We show that evolution of the strong human dPRL promoter was a multistep process that took millions of years. First, MER39 inserted near MER20 in the primate/rodent ancestor, and then there were two phases of activity enhancement in primates. Through the mapping of causal nucleotide substitutions, we demonstrate that strong promoter activity in apes involves epistasis between transcription factor binding sites (TFBSs) ancestral to MER39 and derived sites. We propose a mode of molecular evolution that describes the process by which MER20/MER39 was transformed into a strong promoter, called "epistatic capture." Epistatic capture is the stabilization of a TFBS that is ancestral but variable in outgroup lineages, and is fixed in the ingroup because of epistatic interactions with derived TFBSs. Finally, we note that evolution of human promoter activity coincides with the emergence of a unique reproductive character in apes, highly invasive placentation. Because prolactin communicates with immune cells during pregnancy, which regulate fetal invasion into maternal tissues, we speculate that ape dPRL promoter activity evolved in response to increased invasiveness of ape fetal tissue.cis-regulatory evolution | human evolution | human pregnancy I n the pursuit to understand mechanisms underlying the evolution of gene regulation, it has become increasingly clear that transposable elements play a critical role in regulatory evolution by providing novel genetic elements, including new introns, promoters, enhancers, and insulators (1). In addition to individual examples showing that transposable elements (TEs) are associated with host regulatory function, computational work shows that TEs intersect with many promoter regions (2) and are overrepresented in predicted regulatory regions [(3, 4); see review by Feschotte (1)]. Many questions remain unanswered. How frequently are TEs actually co-opted for regulatory function? What is the adaptive significance of these events? Are TEs used by the host genome immediately upon insertion or do they require extensive sequence evolution before acquiring a biological role? What are the molecular changes that transform a transposable element into a cisregulatory element?In this paper we address the latter two questions posed above by investigating evolution of the decidual prolactin promoter in primates. In a recent paper we showed that the prolactin gene was independently recruited into uterine expression in primates, mice, and elephants by the co-option of different transposable elements, highlighting the frequency at which TEs can be recruited and their importance in gene regulatory innovation (5). Here we trace the evolutionary history and function of transposabl...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Transformation of a transposon into a derived prolactin promoter with function during human pregnancy

Emera

Wagner

2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…These functional attributes enable NK cells to survey the body in search of pathogen-infected or malignant cells and to help protect the host by directly killing such cells as well as by augmenting and recruiting other immune cells. NK cells are known to be important in a variety of clinical settings including viral infection, solid organ and stem cell transplantation (SCT), and pregnancy, among others [2–5]. Given the above as well as recent compelling evidence that NK cells are also capable of immunological memory, there is great interest and rationale in deciphering the process of NK cell development in the hopes of manipulating NK cell numbers and/or functions for therapeutic benefit.…”

Section: What Are Nk Cells?mentioning

confidence: 99%

Location and cellular stages of natural killer cell development

Freud

Caligiuri

2013

Trends in Immunology

299

314

View full text Add to dashboard Cite

The identification of distinct tissue-specific natural killer (NK) cell populations that apparently mature from local precursor populations has brought new insight into the diversity and developmental regulation of this important lymphoid subset. NK cells provide a necessary link between the early (innate) and late (adaptive) immune responses to infection. Gaining a better understanding of the processes that govern NK cell development should allow us to better harness NK cell functions in multiple clinical settings as well as to gain further insight into how these cells undergo malignant transformation. In this review, we summarize recent advances in understanding sites and cellular stages of NK cell development in humans and mice.

show abstract

“…Uterine natural killer (uNK) cells are a subset of NK cells residing in the uterus and play important roles in pregnancy and the development of the placenta [37]. Uterine NK cells have been linked to spiral artery remodeling and produce pro-inflammatory cytokines such as GM-CSF, CSF-1, TNF-α, IFN-γ, TGF-β, LIF and IL-2 and these cytokines have been associated with invasion of trophoblasts into the uterine wall [38, 39].…”

Section: Inflammation Immune Dysfunction and Infertilitymentioning

confidence: 99%

Implications of immune dysfunction on endometriosis associated infertility

et al. 2016

View full text Add to dashboard Cite

Endometriosis is a complex, inflammatory disease that affects 6-10% of reproductive-aged women. Almost half of the women with endometriosis experience infertility. Despite the excessive prevalence, the pathogenesis of endometriosis and its associated infertility is unknown and a cure is not available. While many theories have been suggested to link endometriosis and infertility, a consensus among investigators has not emerged. In this extensive review of the literature as well as research from our laboratory, we provide potential insights into the role of immune dysfunction in endometriosis associated infertility. We discuss the implication of the peritoneal inflammatory microenvironment on various factors that contribute to infertility such as hormonal imbalance, oxidative stress and how these could further lead to poor oocyte, sperm and embryo quality, impaired receptivity of the endometrium and implantation failure.

show abstract

Uterine natural killer (uNK) cells and their missions during pregnancy: A review

Cited by 40 publications

References 152 publications

Transformation of a transposon into a derived prolactin promoter with function during human pregnancy

Transformation of a transposon into a derived prolactin promoter with function during human pregnancy

Location and cellular stages of natural killer cell development

Implications of immune dysfunction on endometriosis associated infertility

Contact Info

Product

Resources

About