Progesterone-Mediated Immunomodulation in Pregnancy: its Relevance to Leukocyte Immunotherapy of Recurrent Miscarriage

Szekeres-Barthó, Júlia

doi:10.2217/imt.09.54

Cited by 46 publications

(27 citation statements)

References 111 publications

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“…Increasing data indicate that the local environment drives them into functionally different subsets. [76][77][78] Chemokine may be the key to regulation of DIC function.…”

Section: Chemokine Instruction To Decidual Immune Cellsmentioning

confidence: 99%

The integrative roles of chemokines at the maternal–fetal interface in early pregnancy

2014

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Embryos express paternal antigens that are foreign to the mother, but the mother provides a special immune milieu at the fetal-maternal interface to permit rather than reject the embryo growth in the uterus until parturition by establishing precise crosstalk between the mother and the fetus. There are unanswered questions in the maintenance of pregnancy, including the poorly understood phenomenon of maternal tolerance to the allogeneic conceptus, and the remarkable biological roles of placental trophoblasts that invade the uterine wall. Chemokines are multifunctional molecules initially described as having a role in leukocyte trafficking and later found to participate in developmental processes such as differentiation and directed migration. It is increasingly evident that the gestational uterine microenvironment is characterized, at least in part, by the differential expression and secretion of chemokines that induce selective trafficking of leukocyte subsets to the maternal-fetal interface and regulate multiple events that are closely associated with normal pregnancy. Here, we review the expression and function of chemokines and their receptors at the maternal-fetal interface, with a special focus on chemokine as a key component in trophoblast invasiveness and placental angiogenesis, recruitment and instruction of immune cells so as to form a fetus-supporting milieu during pregnancy. The chemokine network is also involved in pregnancy complications.

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“…Increasing data indicate that the local environment drives them into functionally different subsets. [76][77][78] Chemokine may be the key to regulation of DIC function.…”

Section: Chemokine Instruction To Decidual Immune Cellsmentioning

confidence: 99%

The integrative roles of chemokines at the maternal–fetal interface in early pregnancy

2014

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“…On the basis of this mechanism, the prevention of recurrent miscarriage relies on finding ways to downregulate pro-inflammatory cytokines and/or to upregulate anti-inflammatory cytokines [11]. Progestogens such as progesterone and dydrogesterone are among the most promising agents for this, with progesterone-induced blocking factor (a molecule produced by a progesterone-induced gene in lymphocytes) implicated in modulating the inhibitory effects of progesterone on cell-mediated immune responses [11][12][13]. The presence of progesterone, and its interaction with progesterone receptors at the decidua level, appears to play a major role in the maternal defense strategy [14].…”

Section: Immunological Factors and Implantationmentioning

confidence: 99%

The role of progesterone in maternal and fetal medicine

Renzo

Giardina

Clerici

et al. 2012

Gynecological Endocrinology

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Progesterone is an essential hormone in the process of reproduction. It has been extensively studied in the treatment of different gynecological pathologies, as a contraceptive and in assisted reproductive technologies. However, the use of progesterone in the pathophysiology of pregnancy remains controversial. Progesterone, and its synthetic form 17 α-hydroxyprogesterone caproate (17 OHP-C), offer an effective intervention when the continuation of pregnancy is at risk from immunological factors, luteinic and neuroendocrine deficiencies, and myometrial hypercontractility. Progesterone has been successfully used as prophylaxis in the prevention of spontaneous miscarriage, with treatment beginning from the first trimester of pregnancy. There is substantial evidence, too, to indicate that women with idiopathic recurrent miscarriage may benefit from the immunomodulatory properties of progesterone in early pregnancy. The use of progesterone and 17 OHP-C has been extensively studied in the prevention of preterm birth in a variety of settings. Transvaginal ultrasound measurement of cervical length in singleton pregnancies between 19 and 24 weeks' gestation has been deemed the best way to identify women (approximately 2% of the pregnant population) who would benefit from prophylactic progesterone treatment for the prevention of spontaneous preterm birth. This paper reviews the evidence for the safety and efficacy of the use of progesterone in each of these indications.

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“…In such conditions, ovarian hyperstimulation as well as a strong supplementation with progesterone (for its immunosuppressive properties) in the mid luteal phase may be useful (Szekeres-Bartho, 2009;Szekeres-Bartho et al, 2009). The place of corticosteroids in such strategies is not clear, with conflicting data on actions in uNK cells.…”

Section: Patients With Excessive Recruitment Of Activated Unk Cellsmentioning

confidence: 99%

New pre-conception immune biomarkers for clinical practice: interleukin-18, interleukin-15 and TWEAK on the endometrial side, G-CSF on the follicular side

Lédée

Petitbarat

Rahmati

et al. 2011

Journal of Reproductive Immunology

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a b s t r a c tIdentification of biomarkers of optimal uterine receptivity to the implanting embryo as well as biomarkers of oocyte competence would undoubtedly improve the efficiency of assisted reproductive technology (ART). Expression of IL-15 and IL-18 has been shown to be different in patients with failed implantation after IVF/ICSI compared with fertile controls and both correlate with local uNK (CD56+) recruitment and angiogenesis. Tumor necrosis factor weak inducer of apoptosis (TWEAK) has been described in mice as a potent early immune regulator able to protect the conceptus. The results of our studies in human suggest that TWEAK modulates the IL-18 related cytotoxicity of uNK cells. Quantification of IL-18, TWEAK and IL-15 mRNA expression by real-time PCR in endometrial tissue collected in midluteal phase of non-conception cycles allowed documentation of physiological events that occur at the time of uterine receptivity. Such information may be useful for the physician especially in patients where embryos fail to implant. Cytokine quantification may assist in understanding the mechanisms leading to repeated IVF/ICSI failure: either depletion of cytokines necessary for the apposition-adhesion, or an excess of cytokines leading to local cytotoxicity, may impair the implantation of the embryo. Other new data suggest that a pre-conception dialogue mediated by the oocyte and the follicular fluid and the oocyte may contribute to later implantation success. Follicular concentration of G-CSF appears as a useful biomarker of oocyte competence before fertilization. Moreover both in human and animal models, evidence of a role of the endometrium as a biosensor of the embryo is emerging.

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Progesterone-Mediated Immunomodulation in Pregnancy: its Relevance to Leukocyte Immunotherapy of Recurrent Miscarriage

Cited by 46 publications

References 111 publications

The integrative roles of chemokines at the maternal–fetal interface in early pregnancy

The integrative roles of chemokines at the maternal–fetal interface in early pregnancy

The role of progesterone in maternal and fetal medicine

New pre-conception immune biomarkers for clinical practice: interleukin-18, interleukin-15 and TWEAK on the endometrial side, G-CSF on the follicular side

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