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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)

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

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 serum PIBF. Neither a synthetic progestin (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.

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Acknowledgments

Actavis (Parsippany, NJ) Pharmaceutical Company provided some funds that were used to purchase reagents for some of the studies. The authors are not on the payroll of any pharmaceutical companies or have any connection with any manufacturer of laboratory tests. None of the authors have filed a patent for the production of the PIBF assay.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA

    Rachael A. Cohen

  2. Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Cooper Medical School of Rowan University, Camden, NJ, USA

    Jerome H. Check

  3. Department of Obstetrics, Gynecology and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA

    Michael P. Dougherty

  4. 7447 Old York Road, Melrose Park, PA, 19027, USA

    Jerome H. Check

Authors
  1. Rachael A. Cohen
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  2. Jerome H. Check
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  3. Michael P. Dougherty
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Corresponding author

Correspondence to Jerome H. Check.

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Statement of human rights

The study has been approved by a Western IRB (protocol number 20121249, CIR 110). The studies have been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Additional information

Capsule

A rise in serum progesterone independent of a conception seems to be the main stimulus for causing a significant rise in the immunomodulatory protein, the progesterone induced blocking factor.

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Cohen, R.A., Check, J.H. & Dougherty, M.P. 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). J Assist Reprod Genet 33, 221–229 (2016). https://doi.org/10.1007/s10815-015-0619-7

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  • DOI: https://doi.org/10.1007/s10815-015-0619-7

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