1.
Immune responses in the human female reproductive tract.
Monin, L, Whettlock, EM, Male, V
Immunology. 2020;(2):106-115
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Abstract
Mucosal surfaces are key interfaces between the host and its environment, but also constitute ports of entry for numerous pathogens. The gut and lung mucosae act as points of nutrient and gas exchange, respectively, but the physiological purpose of the female reproductive tract (FRT) is to allow implantation and development of the fetus. Our understanding of immune responses in the FRT has traditionally lagged behind our grasp of the situation at other mucosal sites, but recently reproductive immunologists have begun to make rapid progress in this challenging area. Here, we review current knowledge of immune responses in the human FRT and their heterogeneity within and between compartments. In the commensal-rich vagina, the immune system must allow the growth of beneficial microbes, whereas the key challenge in the uterus is allowing the growth of the semi-allogeneic fetus. In both compartments, these objectives must be balanced with the need to eliminate pathogens. Our developing understanding of immune responses in the FRT will help us develop interventions to prevent the spread of sexually transmitted diseases and to improve outcomes of pregnancy for mothers and babies.
2.
Understanding vitamin D metabolism in pregnancy: From physiology to pathophysiology and clinical outcomes.
Karras, SN, Wagner, CL, Castracane, VD
Metabolism: clinical and experimental. 2018;:112-123
Abstract
This critical time frame of intrauterine life development is considered of major importance on the metabolic imprinting of overall health of the offspring, in later life. This requires a delicate immune balance that nurtures the allogeneic fetus, while maintaining reactivity against pathogens. Dysregulation of these tightly controlled biophenomena at a systemic and placental level, have been considered as a potential mechanism mediating pathogenesis of preeclampsia and spontaneous birth. In this context, vitamin D has been considered as a significant regulator of both innate and adaptive immunity by regulating cell proliferation, differentiation and apoptosis. Vitamin D metabolism during pregnancy manifests striking differences as compared to the non-pregnant state. Calcitriol is increasing >2-3 fold in the first weeks of pregnancy whereas maternal 25-hydroxyvitamin D crosses the placental barrier and represents the main pool of vitamin D in the fetus. Moreover, during pregnancy, vitamin D receptor and regulatory metabolic enzymes are expressed in the placenta and decidua, indicating a potential critical point in the immunomodulation at the maternal-fetal interface. Considering these effects, maternal hypovitaminosis D during pregnancy has been associated with pregnancy related disorders. This review focuses on the mechanistic basis of these adaptive changes, as a background for the development of pregnancy related disorders, with a discourse on the pathophysiology relating hypovitaminosis D and clinical outcomes.
3.
Vitamin D, autoimmunity and recurrent pregnancy loss: More than an association.
Sharif, K, Sharif, Y, Watad, A, Yavne, Y, Lichtbroun, B, Bragazzi, NL, Amital, H, Shoenfeld, Y
American journal of reproductive immunology (New York, N.Y. : 1989). 2018;(3):e12991
Abstract
Recurrent pregnancy loss (RPL) affects close to 1% of couples; however, the etiology is known in only about 50% of the cases. Recent studies show that autoimmune dysregulation is a probable cause of RPL, which in some cases may be overlooked. In order for a pregnancy to proceed to term, early modulation of immunologic response is required to induce tolerance to the semi-allogenic fetus. Certain subsets of both the innate and adaptive immune responses play a role in the induction of fetomaternal tolerance. A relatively predominant T-cell helper (Th) 2 and T regulatory (Treg) cell population seem to favor a better pregnancy outcome, whereas Th1 and Th17 cell populations appear to have an opposite effect. Lately, the role of vitamin D in the modulation of immune response was established. Vitamin D has been shown to promote a more favorable environment for pregnancy through various mechanisms, such as enhancement of the shift toward Th2 cells and regulation of immune cell differentiation and cytokine secretion. Therefore, it seems that vitamin D deficiency sways the balance toward a worse outcome and may play a part in recurrent pregnancy loss. This review sheds light on the immunologic changes, which occur in early pregnancy and the regulatory role vitamin D has in the maintenance of this delicate balance.
4.
The Pregnancy Microbiome.
Neuman, H, Koren, O
Nestle Nutrition Institute workshop series. 2017;:1-9
Abstract
In recent years, microbiome research has revealed multiple essential roles of the microorganisms residing within the human body in host metabolism, immunity, and overall health. Numerous physiological and pathological states, including obesity and the metabolic syndrome, have been correlated with microbial changes, termed dysbiosis. Our microbiomes change in response to our environment, diet, weight, hormones, and other factors. It is, therefore, not surprising that there are also significant changes in the microbiome during pregnancy when dramatic weight gain and metabolic and immunological changes occur. In this review, we summarize the known changes in microbial composition throughout pregnancy at a variety of body sites, including the gut, vagina, oral cavity, and placenta, and we describe several studies that have linked pregnancy complications with microbial changes. Unlike the case of certain disease states, such as obesity, where dysbiosis is considered to have negative effects, we believe that the microbial alterations observed during pregnancy are vital for a healthy pregnancy. While more research in this field is required to reveal specific mechanisms and pathways regulating these alterations, the microbial changes during pregnancy are likely coordinated with the immune, endocrine, and metabolic states.