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The Role of Progesterone in the Feto-Maternal Immunological Relationship
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The Role of Progesterone in the Feto-Maternal Immunological Relationship

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 43264

Special Issue Editors

Prof. Dr. Julia Szekeres-Bartho

E-Mail Website
Guest Editor
National Laboratory for Human Reproduction, University of Pécs, 7624 Pécs, Hungary
Interests: blocking factor; habitual abortion; progesterone; trophoblasts; decidua; natural killer cells
Special Issues, Collections and Topics in MDPI journals
Dr. Nandor Gabor Than

E-Mail Website
Guest Editor
Systems Biology of Reproduction Research Group, Institute of Enzymology, Research Center for Natural Sciences, Budapest, Hungary
Interests: pregnancy complications; miscarriage; preeclampsia; gestational trophoblastic disease; placenta; placental protein; galectin; perinatology; reproductive biology and immunology; systems biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pregnancy represents a unique immunological situation. Though paternal antigens expressed by the conceptus are recognized by the immune system of the mother, the resulting immune response does not harm the fetus. Progesterone and a progesterone-induced protein, PIBF, play important roles in the readjustment of the functioning of the maternal immune system during pregnancy.

Progesterone is indispensable to the initiation as well as the maintenance of pregnancy. This hormone is required for decidual transformation of the endometrial stroma and uterine quiescence in myometrial smooth muscle cells. It supports the physiological functions of the uterine cervix, controls the invasiveness of the embryonic trophoblast and malignant tumors, and has a profound effect on the maternal anti-fetal immune response.

Our increasing knowledge of the diverse actions of progesterone can be translated into clinical treatments for various pregnancy disorders, e.g., recurrent implantation failure, recurrent miscarriage, preterm labor syndrome, and preeclampsia.

This Special Issue will cover the role of progesterone in the feto-maternal immunological interaction as well as its possible clinical implications.

Prof. Dr. Julia Szekeres-Bartho
Dr. Nandor Gabor Than
Guest Editors

Manuscript Submission Information

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Keywords

  • progesterone
  • progesterone receptor
  • cytokine
  • NK cell
  • recurrent implantation failure
  • recurrent miscarriage
  • preterm labor syndrome
  • preeclampsia

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Published Papers (4 papers)

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Research

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18 pages, 1893 KiB  
Article
Early-Pregnancy Dydrogesterone Supplementation Mimicking Luteal-Phase Support in ART Patients Did Not Provoke Major Reproductive Disorders in Pregnant Mice and Their Progeny
by Laura Jeschke, Clarisa Guillermina Santamaria, Nicole Meyer, Ana Claudia Zenclussen, Julia Bartley and Anne Schumacher
Int. J. Mol. Sci. 2021, 22(10), 5403; https://doi.org/10.3390/ijms22105403 - 20 May 2021
Cited by 5 | Viewed by 4758
Abstract
Progestogens are frequently administered during early pregnancy to patients undergoing assisted reproductive techniques (ART) to overcome progesterone deficits following ART procedures. Orally administered dydrogesterone (DG) shows equal efficacy to other progestogens with a higher level of patient compliance. However, potential harmful effects of [...] Read more.
Progestogens are frequently administered during early pregnancy to patients undergoing assisted reproductive techniques (ART) to overcome progesterone deficits following ART procedures. Orally administered dydrogesterone (DG) shows equal efficacy to other progestogens with a higher level of patient compliance. However, potential harmful effects of DG on critical pregnancy processes and on the health of the progeny are not yet completely ruled out. We treated pregnant mice with DG in the mode, duration, and doses comparable to ART patients. Subsequently, we studied DG effects on embryo implantation, placental and fetal growth, fetal-maternal circulation, fetal survival, and the uterine immune status. After birth of in utero DG-exposed progeny, we assessed their sex ratios, weight gain, and reproductive performance. Early-pregnancy DG administration did not interfere with placental and fetal development, fetal-maternal circulation, or fetal survival, and provoked only minor changes in the uterine immune compartment. DG-exposed offspring grew normally, were fertile, and showed no reproductive abnormalities with the exception of an altered spermiogram in male progeny. Notably, DG shifted the sex ratio in favor of female progeny. Even though our data may be reassuring for the use of DG in ART patients, the detrimental effects on spermatogenesis in mice warrants further investigations and may be a reason for caution for routine DG supplementation in early pregnancy. Full article
(This article belongs to the Special Issue The Role of Progesterone in the Feto-Maternal Immunological Relationship)
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Review

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16 pages, 595 KiB  
Review
Progesterone: A Unique Hormone with Immunomodulatory Roles in Pregnancy
by Raj Raghupathy and Julia Szekeres-Bartho
Int. J. Mol. Sci. 2022, 23(3), 1333; https://doi.org/10.3390/ijms23031333 - 25 Jan 2022
Cited by 54 | Viewed by 12130
Abstract
Progesterone is well known for its numerous endocrinologic roles in pregnancy but is also endowed with fascinating immunomodulatory capabilities. It can downregulate the induction of inflammatory reactions, the activation of immune cells and the production of cytokines, which are critical mediators of immune [...] Read more.
Progesterone is well known for its numerous endocrinologic roles in pregnancy but is also endowed with fascinating immunomodulatory capabilities. It can downregulate the induction of inflammatory reactions, the activation of immune cells and the production of cytokines, which are critical mediators of immune responses. These features appear to be critical to the success of pregnancy, given the ability of maternal immune reactivity to interfere with pregnancy and to contribute to several pregnancy complications. This review summarizes the contribution of maternal immune effectors in general, and cytokines in particular, to pregnancy complications such as recurrent miscarriage, pre-eclampsia and preterm labor; it describes the promise offered by supplementation with progesterone and the oral progestogen dydrogesterone, as well as the progesterone-induced blocking factor in the prevention and/or treatment of these serious complications. Full article
(This article belongs to the Special Issue The Role of Progesterone in the Feto-Maternal Immunological Relationship)
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18 pages, 3302 KiB  
Review
A Hypothetical Model Suggesting Some Possible Ways That the Progesterone Receptor May Be Involved in Cancer Proliferation
by Jerome H. Check and Diane L. Check
Int. J. Mol. Sci. 2021, 22(22), 12351; https://doi.org/10.3390/ijms222212351 - 16 Nov 2021
Cited by 5 | Viewed by 2545
Abstract
Cancer and the fetal-placental semi-allograft share certain characteristics, e.g., rapid proliferation, the capacity to invade normal tissue, and, related to the presence of antigens foreign to the host, the need to evade immune surveillance. Many present-day methods to treat cancer use drugs that [...] Read more.
Cancer and the fetal-placental semi-allograft share certain characteristics, e.g., rapid proliferation, the capacity to invade normal tissue, and, related to the presence of antigens foreign to the host, the need to evade immune surveillance. Many present-day methods to treat cancer use drugs that can block a key molecule that is important for one or more of these characteristics and thus reduce side effects. The ideal molecule would be one that is essential for both the survival of the fetus and malignant tumor, but not needed for normal cells. There is a potential suitable candidate, the progesterone induced blocking factor (PIBF). The parent 90 kilodalton (kDa) form seems to be required for cell-cycle regulation, required by both the fetal-placental unit and malignant tumors. The parent form may be converted to splice variants that help both the fetus and tumors escape immune surveillance, especially in the fetal and tumor microenvironment. Evidence suggests that membrane progesterone receptors are involved in PIBF production, and indeed there has been anecdotal evidence that progesterone receptor antagonists, e.g., mifepristone, can significantly improve longevity and quality of life, with few side effects. Full article
(This article belongs to the Special Issue The Role of Progesterone in the Feto-Maternal Immunological Relationship)
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14 pages, 1361 KiB  
Review
Key to Life: Physiological Role and Clinical Implications of Progesterone
by Bernadett Nagy, Júlia Szekeres-Barthó, Gábor L. Kovács, Endre Sulyok, Bálint Farkas, Ákos Várnagy, Viola Vértes, Kálmán Kovács and József Bódis
Int. J. Mol. Sci. 2021, 22(20), 11039; https://doi.org/10.3390/ijms222011039 - 13 Oct 2021
Cited by 49 | Viewed by 22465
Abstract
The most recent studies of progesterone research provide remarkable insights into the physiological role and clinical importance of this hormone. Although the name progesterone itself means “promoting gestation”, this steroid hormone is far more than a gestational agent. Progesterone is recognized as a [...] Read more.
The most recent studies of progesterone research provide remarkable insights into the physiological role and clinical importance of this hormone. Although the name progesterone itself means “promoting gestation”, this steroid hormone is far more than a gestational agent. Progesterone is recognized as a key physiological component of not only the menstrual cycle and pregnancy but also as an essential steroidogenic precursor of other gonadal and non-gonadal hormones such as aldosterone, cortisol, estradiol, and testosterone. Based on current findings, progesterone and novel progesterone-based drugs have many important functions, including contraception, treatment of dysfunctional uterine bleeding, immune response, and prevention of cancer. Considering the above, reproduction and life are not possible without progesterone; thus, a better understanding of this essential molecule could enable safe and effective use of this hormone in many clinical conditions. Full article
(This article belongs to the Special Issue The Role of Progesterone in the Feto-Maternal Immunological Relationship)
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