Evidence that exposure to progesterone alone is a sufficient stimulus to cause a precipitous rise in the immunomodulatory protein the progesterone induced blocking factor (PIBF)

Abstract

Purpose To determine if exposure to progesterone alone is sufficient to increase the production of the immunomodulatory protein known as the progesterone induced blocking factor (PIBF). Also to determine what method of progesterone delivery or form of P best stimulates PIBF secretion. Methods Serum samples from patients with infertility and paid volunteers were evaluated for both PIBF and progesterone at various times during the follicular phase and the luteal phase in both natural cycles and cycles involving embryo transfer after endogenous and exogenous progesterone exposure and after various synthetic progestins. PIBF was measured by a non-commercial research ELISA assay. Comparisons were made of serum PIBF before and after exposure to progesterone, 17-hydroxyprogesterone, and oral contraceptives. PIBF was also measured before and after transfer of embryos.Results Progesterone alone without exposure to the fetal allogeneic stimulus was able to produce a marked increase in s e r u m P I B F. N e i t h e r a s y n t h e t i c p r o g e s t i n (19-nortestosterone derivative) nor 17-hydroxyprogesterone caused an increase in PIBF. Some PIBF is generally detected even in the follicular phase. Conclusions A previous concept considered that an allogeneic stimulus, e.g., from the fetal semi-allograft, was necessary to induce de novo progesterone receptors in gamma delta T cells, which, in turn, when exposed to a high concentration of progesterone, would secrete high levels of PIBF. These data show that exposure to an allogeneic stimulus is not needed to cause a marked rise in PIBF, merely progesterone alone is sufficient.

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

“…This dose dependent relationship between progesterone and PIBF is evidenced by the significant positive correlation between the two biomarkers seen in this study. The correlation is consistent with other studies that demonstrate increases in PIBF caused by progesterone 37 .…”

Changes in T Cell and Dendritic Cell Phenotype from Mid to Late Pregnancy Are Indicative of a Shift from Immune Tolerance to Immune Activation

“…Progesterone is important for the establishment and maintenance of pregnancy and exerts immune-modulatory effects mediated by the lymphocyte-derived protein progesterone-induced blocking factor (PIBF) ( 31 , 32 ). Effector functions modulated by PIBF include cytokine synthesis, cytotoxic cell activity, and arachidonic acid synthesis ( 6 , 31 , 33 ).…”

NLRP3 inflammasome as the potential target mechanism and therapy in recurrent spontaneous abortions

“…The exact mechanism of RSA is remains unclear. Certain studies have suggested that the onset of RSA has been associated with maternal immune system attack on the fetus by allo-rejection (27)(28)(29). A previous study observed that Th2-anti-inflammatory predominance facilitated the survival of the fetus in the maternal uterus (30).…”