PlGF Immunological Impact during Pregnancy

Abstract

During pregnancy, the mother’s immune system has to tolerate the persistence of paternal alloantigens without affecting the anti-infectious immune response. Consequently, several mechanisms aimed at preventing allograft rejection, occur during a pregnancy. In fact, the early stages of pregnancy are characterized by the correct balance between inflammation and immune tolerance, in which proinflammatory cytokines contribute to both the remodeling of tissues and to neo-angiogenesis, thus, favoring the correct embryo implantation. In addition to the creation of a microenvironment able to support both immunological privilege and angiogenesis, the trophoblast invades normal tissues by sharing the same behavior of invasive tumors. Next, the activation of an immunosuppressive phase, characterized by an increase in the number of regulatory T (Treg) cells prevents excessive inflammation and avoids fetal immuno-mediated rejection. When these changes do not occur or occur incompletely, early pregnancy failure follows. All these events are characterized by an increase in different growth factors and cytokines, among which one of the most important is the angiogenic growth factor, namely placental growth factor (PlGF). PlGF is initially isolated from the human placenta. It is upregulated during both pregnancy and inflammation. In this review, we summarize current knowledge on the immunomodulatory effects of PlGF during pregnancy, warranting that both innate and adaptive immune cells properly support the early events of implantation and placental development. Furthermore, we highlight how an alteration of the immune response, associated with PlGF imbalance, can induce a hypertensive state and lead to the pre-eclampsia (PE).

Biomolecular Markers of Recurrent Implantation Failure—A Review

“…Th1/Th2 imbalance elevated number and activity of peripheral and uterine NK cells elevated activity of Th1 cells and elevated levels of cytokines produced by Th1 cells (TNF-α)-inflammatory promoting, trophoblastic growth suppression, thrombotic responses in maternal uterine blood vessels, embryo rejection [9,41,80] Infection chronic endometritis-Escherichia coli, Enterococcus faecalis, group B Streptococcus, Mycoplasma, Chlamydia [18,19,77,105] Inherited thrombophilia carrying of factor V Leiden mutation, deficiency of MTHFR, PTM and ATIII [27,[84][85][86] Molecules expression LIF-decreased level leads to influence the reproductive capacity VEGF-reduced expression in peri-implantation period in RIF PlGF-decreasing concentration in RIF [46,50,70,74,76] Genetics factors microRNAs-function modulators, control the expression of genes involved in peri-implantation period [28,83] factor V Leiden mutation, MTHFR mutation-the role in IVF-embryo transfer and implantation failure [27,84] p53-genetic polymorphisms modulate the biological activity of protein p53, leading to lower rate of implantation success [14,30,[87][88][89][90][91][92]119] HLA-G-genetic polymorphisms modulate immune system influencing fertilization process [14,31] VEGF-genetic polymorphisms involved in angiogenesis process, support the successful implantation [29,92] ESR1-genetic polymorphisms associated with the implantation process [67] ATIII, antithrombin III; BMI, body mass index; ESR1, estrogen receptor 1; HLA-G, human leukocyte antigen G; LIF, leukemia inhibitor factor; MTHFR, methylene tetr...…”

“…PlGF is reported to be associated with pathological angiogenesis, which occurs in inflammatory processes and tumor angiogenesis [ 79 ]. The decreasing concentration of PlGF in preeclamptic women suggests that this molecule could predict occurrence of the disease [ 80 , 81 ]. It was suggested that PlGF could play an important role in uterine NK cell proliferation, as well as in differentiation.…”

Immunoendocrine Dysregulation during Gestational Diabetes Mellitus: The Central Role of the Placenta

“…Other important pro-angiogenic factors produced by placenta are the PlGF, which can also activate VEGFR1, neuropilin-1 (NRP-1), angiopoietins, fibroblast growth factor 2, platelet derived growth factor, and the insulin/IGF axis [ 225 , 226 , 227 , 228 ]. As mentioned before, HIF-1α is a major driver of VEGF transcription, however in vitro studies demonstrated PlGF is not regulated by this factor in the human placenta [ 229 ]. In trophoblast cells, PlGF expression decreases in low oxygen tension conditions, whereas normoxic conditions increase PlGF contrary to what occurs in other cell types [ 230 ].…”

Peran Imunitas Seluler Pada Ibu Hamil

“…15 Akan tetapi peningkatan dari sel T CD8+ bisa juga merugikan janin, karena aktifitas sitotoksik yang berlebihan akan membuat janin terdampak dan bisa sampai keguguran. 20 Sel T CD4+ yang akan berdiferensiasi menjadi sel T helper juga memiliki peran penting dalam proses sel imun pada saat hamil. Sel T helper melakukan signaling pada sel T CD8+ untuk melakukan proses sitotoksik.…”

“…17 Akan tetapi keadaan imunosupresif ini juga bisa berakibat buruk dikarenakan ibu dan janin menjadi rentan terhadap agen infeksi seperti virus. 19,20 Keadaan khusus dijumpai pada beberapa laporan penelitian. Penyakit dari virus corona seperti MERS, SARS dan COVID-19 pada masa kehamilan membuat respon imun seluler menjadi kacau.…”