Immunological Changes in Pregnancy and Prospects of Therapeutic Pla-Xosomes in Adverse Pregnancy Outcomes

Abstract

Stringent balance of the immune system is a key regulatory factor in defining successful implantation, fetal development, and timely parturition. Interference in these primary regulatory mechanisms, either at adolescence or prenatal state led to adverse pregnancy outcomes. Fertility restoration with the help of injectable gonadotrophins/progesterone, ovulation-inducing drugs, immunomodulatory drugs (corticosteroids), and reproductive surgeries provides inadequate responses, which manifest its own side effects. The development of a potential diagnostic biomarker and an effectual treatment for adverse pregnancy outcomes is a prerequisite to maternal and child health. Parent cell originated bi-layered-intraluminal nano-vesicles (30–150 nm) also known as exosomes are detected in all types of bodily fluids like blood, saliva, breast milk, urine, etc. Exosomes being the most biological residual structures with the least cytotoxicity are loaded with cargo in the form of RNAs (miRNAs), proteins (cytokines), hormones (estrogen, progesterone, etc.), cDNAs, and metabolites making them chief molecules of cell-cell communication. Their keen involvement in the regulation of biological processes has portrayed them as the power shots of cues to understand the disease’s pathophysiology and progression. Recent studies have demonstrated the role of immunexosomes (immunomodulating exosomes) in maintaining unwavering immune homeostasis between the mother and developing fetus for a healthy pregnancy. Moreover, the concentration and size of the exosomes are extensively studied in adverse pregnancies like preeclampsia, gestational diabetes mellitus (GDM), and preterm premature rupture of membrane (pPROMs) as an early diagnostic marker, thus giving in-depth information about their pathophysiology. Exosomes have also been engineered physically as well as genetically to enhance their encapsulation efficiency and specificity in therapy for cancer and adverse pregnancies. Successful bench to bedside discoveries and interventions in cancer has motivated developmental biologists to investigate the role of immunexosomes and their active components. Our review summarizes the pre-clinical studies for the use of these power-shots as therapeutic agents. We envisage that these studies will pave the path for the use of immunexosomes in clinical settings for reproductive problems that arise due to immune perturbance in homeostasis either at adolescence or prenatal state.

Human amniotic fluid derived extracellular vesicles attenuate T cell immune response

“…During pregnancy the maternal immune system is altered to suppress the immune response to develop tolerance to proliferating cells from the fetus ( 39 , 40 ), and some of these immunological changes can be observed within T cell populations. For example, there is a decrease in the overall CD3+ T cell population, CD4+ T cells, and CD8+ T cells during late pregnancy compared to before pregnancy ( 41 , 42 ). There is also a reduction of PHA induced T cell proliferation in pregnant women compared to non-pregnant controls ( 43 ).…”

“…There is also a reduction of PHA induced T cell proliferation in pregnant women compared to non-pregnant controls ( 43 ). Many of these immunological changes during pregnancy are mediated through EV signaling within the placenta ( 41 ). Therefore, it is not surprising that EVs derived from perinatal tissue or AF would promote immunosuppression under certain environmental conditions.…”

Inflammation in recurrent miscarriage — a comprehensive perspective from uterine microenvironment and immune cell imbalance to therapeutic strategies

“…Furthermore, the increased number of NK cells in the uterus of women with recurrent miscarriage may lead to an imbalance of the immune response, which in turn affects the implantation and growth of the embryo [77]. This imbalance may be due to the womb NK cells and other immune cells, such as T cells and macrophages, the interaction between is broken [78,79]. Study also found that the NK cells in peripheral blood of pregnant women during pregnancy can absorb microRNAs associated with placenta, these microRNAs play A key role in regulating gene expression [80].…”

Maternal and Neonatal Outcomes in Pregnancies Positive for SARS-CoV-2

“…A decline in the acute immune response to inflammation occurs as a protective mechanism against fetal rejection. These alterations in the body's cardiopulmonary immune system make pregnant mothers more prone to viruses (5). Additionally, both mechanical and biochemical factors influence gas exchange and pulmonary function throughout pregnancy, such as the decrease in residual volume.…”