Characterisation of serum progesterone and progesterone-induced blocking factor (PIBF) levels across trimesters in healthy pregnant women

Lim, Mark Kit; Ku, Chee Wai; Tan, Thiam Chye; Lee, Yin Hao Justin; Allen, John C.; Tan, Nguan Soon

doi:10.1038/s41598-020-59452-y

Cited by 24 publications

(27 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The authors concluded that these effects on blood pressure and inflammation were brought about by PIBF normalizing the levels of Th2 cells. Serum concentrations of PIBF in normal human pregnancy increase with gestational age; lower than normal concentrations are associated with spontaneous termination of pregnancy [134]; failure to detect PIBF at 3 to 5 weeks of gestation has been shown to be associated with a higher rate of miscarriage [135]. In fact, the decidual expression of PIBF and serum levels of PIBF in women with unexplained miscarriages are significantly lower than those in healthy pregnant women, pointing to important beneficial roles of PIBF [136].…”

Section: Progesterone-induced Blocking Factor (Pibf)mentioning

confidence: 99%

Progesterone: A Unique Hormone with Immunomodulatory Roles in Pregnancy

Raghupathy

Szekeres-Barthó

2022

IJMS

View full text Add to dashboard Cite

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.

show abstract

Section: Progesterone-induced Blocking Factor (Pibf)mentioning

confidence: 99%

Progesterone: A Unique Hormone with Immunomodulatory Roles in Pregnancy

Raghupathy

Szekeres-Barthó

2022

IJMS

View full text Add to dashboard Cite

show abstract

“…In IVF patients PIBF is detectable in the serum 14 days after embryo transfer (36). During normal human pregnancy, the serum concentrations of PIBF increase with gestational age; lower than normal concentrations predict spontaneous pregnancy termination (37,38). In women with unexplained miscarriages decidual PR and PIBF expression, as well as serum PIBF concentrations are significantly lower than in healthy pregnant women and all of these parameters show a positive correlation with the number of peripheral g d T cells (39).…”

Section: Progesterone-dependent Immunoregulationmentioning

confidence: 99%

Cytokines, Hormones and Cellular Regulatory Mechanisms Favoring Successful Reproduction

et al. 2021

View full text Add to dashboard Cite

Its semi-allogeneic nature renders the conceptus vulnerable to attack by the maternal immune system. Several protective mechanisms operate during gestation to correct the harmful effects of anti-fetal immunity and to support a healthy pregnancy outcome. Pregnancy is characterized by gross alterations in endocrine functions. Progesterone is indispensable for pregnancy and humans, and it affects immune functions both directly and via mediators. The progesterone-induced mediator - PIBF - acts in favor of Th2-type immunity, by increasing Th2 type cytokines production. Except for implantation and parturition, pregnancy is characterized by a Th2-dominant cytokine pattern. Progesterone and the orally-administered progestogen dydrogesterone upregulate the production of Th2-type cytokines and suppress the production of Th1 and Th17 cytokine production in vitro. This is particularly relevant to the fact that the Th1-type cytokines TNF-α and IFN-γ and the Th17 cytokine IL-17 have embryotoxic and anti-trophoblast activities. These cytokine-modulating effects and the PIBF-inducing capabilities of dydrogesterone may contribute to the demonstrated beneficial effects of dydrogesterone in recurrent spontaneous miscarriage and threatened miscarriage. IL-17 and IL-22 produced by T helper cells are involved in allograft rejection, and therefore could account for the rejection of paternal HLA-C-expressing trophoblast. Th17 cells (producing IL-17 and IL-22) and Th22 cells (producing IL-22) exhibit plasticity and could produce IL-22 and IL-17 in association with Th2-type cytokines or with Th1-type cytokines. IL-17 and IL-22 producing Th cells are not harmful for the conceptus, if they also produce IL-4. Another important protective mechanism is connected with the expansion and action of regulatory T cells, which play a major role in the induction of tolerance both in pregnant women and in tumour-bearing patients. Clonally-expanded Treg cells increase at the feto-maternal interface and in tumour-infiltrating regions. While in cancer patients, clonally-expanded Treg cells are present in peripheral blood, they are scarce in pregnancy blood, suggesting that fetal antigen-specific tolerance is restricted to the foeto-maternal interface. The significance of Treg cells in maintaining a normal materno-foetal interaction is underlined by the fact that miscarriage is characterized by a decreased number of total effector Treg cells, and the number of clonally-expanded effector Treg cells is markedly reduced in preeclampsia. In this review we present an overview of the above mechanisms, attempt to show how they are connected, how they operate during normal gestation and how their failure might lead to pregnancy pathologies.

show abstract

“…PIBF is present in the urine and the sera of pregnant women. In serum samples of in vitro fertilization (IVF) patients PIBF was detected 14 days after embryo transfer [67], and later the serum concentrations increased by gestational age in uneventful pregnancies [68]. Lower than normal concentrations predict spontaneous pregnancy termination [69,70] as shown by the finding that not only decidual PR and PIBF expression, but also the serum concentrations of PIBF are characteristically low in women with unexplained miscarriages in [71].…”

Section: Pibf In Pregnancymentioning

confidence: 99%

Progesterone induced blocking factor in health and disease

Szekeres-Barthó

2021

Explor Immunol

View full text Add to dashboard Cite

The foetus expressing paternal antigens ought to be “rejected” by the maternal immune system. However, the immunological relationship of the mother and the foetus does not follow the rules of transplantation immunology. Maternal immune functions are re-adjusted during pregnancy, to create a tolerant environment for the developing foetus. Progesterone and its downstream mediator; the progesterone induced blocking factor (PIBF) are important in this process. The mRNA transcribed from the PIBF1 gene contains 18 exons, and codes for a 90 kDa protein. The 90 kDa form is associated with the centrosome and plays a role in cell cycle regulation, while smaller isoforms produced by alternative spicing are secreted, and bind to the glycosylphosphatidylinositol (GPI) anchored PIBF receptor. Upon ligation, the former forms a heterodimer with the alpha chain of the interleukin-4 (IL-4) receptor and activates the Janus kinase/signal transducers and activators of transcription (Jak/STAT) pathway, via which, PIBF induces increased production of T helper2 (Th2) cytokines. PIBF regulates natural killer (NK) cytotoxicity, by inhibiting perforin release from the cytoplasmic granules of NK cells. During normal human pregnancy, the serum concentrations of PIBF increase with gestational age, and lower than normal serum levels predict spontaneous pregnancy termination. Depletion of PIBF during the peri-implantation period in mice, results in lower implantation and increased resorption rates, together with increased decidual and peripheral NK activity, downregulation of the genes implicated in T cell activation in CD4+ cells, and Th1 differentiation of the T cells. PIBF is expressed in rapidly proliferating immature cells as well as several tumours, and regulates invasion. The PIBF gene has been identified in the chromosomal region 13q21-q22—which is a common site for somatic deletions in a variety of malignant tumours. These data suggest that PIBF might be involved in tumorigenesis.

show abstract

Characterisation of serum progesterone and progesterone-induced blocking factor (PIBF) levels across trimesters in healthy pregnant women

Cited by 24 publications

References 51 publications

Progesterone: A Unique Hormone with Immunomodulatory Roles in Pregnancy

Progesterone: A Unique Hormone with Immunomodulatory Roles in Pregnancy

Cytokines, Hormones and Cellular Regulatory Mechanisms Favoring Successful Reproduction

Progesterone induced blocking factor in health and disease

Contact Info

Product

Resources

About