# PROSTAGLANDINS & PAF IN ZYGOTE DEVELOPMENT & ATTACHMENT

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 1994 · $117,960

## Abstract

Platelet-activating factor (PAF) is a pro-inflammatory lipid which is a
potent inducer of vascular permeability that has been implicated as an
essential component of pre-implantation stages of pregnancy.  Both embryo-
derived and uterine PAF have been suggested as key regulators for
establishment of pregnancy.  However, these claims are controversial.  In
some instances, published claims have been unable to be confirmed.  We have
established that PAF levels in rabbit endometrium change during early
pregnancy and pseudopregnancy, and that rabbit endometrial membranes have
high affinity binding sites for PAF.  Furthermore, human endometrial
stromal cells in culture make PAF, and their cellular content of PAF can be
elevated by progesterone, and further amplified by prostaglandin E2 (PGE2).
Conversely, in endometrial epithelial cells, PGE2 secretion is increased
and PGF2alpha secretion inhibited by addition of PAF, suggesting the
presence of a paracrine control mechanism between epithelial and stromal
cells.  Isolated rabbit endometrial cells also produce PAF in response to
A23187 treatment, and there appears to be a difference in responsiveness
between cells derived from day-6 of pregnancy and pseudopregnancy.  We have
further shown that a PAF antagonist CV3988 can inhibit implantation in
rabbits, probably by an endometrial action, and that day-6 blastocysts
respond to PAF in vitro by phospholipid turnover and increased
intracellular calcium levels.

The present research will determine the significance of PAG in the
implantation process in rabbits.  Various PAF antagonists, that compete or
do not compete, with endometrial PAF receptors will be tested for ability
to interfere with implantation when given at various times during pre-
implantation pregnancy.  Reversal of any such inhibition will be attempted
by concomitant administration of a non-metabolizable PAF analog.  These
experiments will determine the specificity of this inhibitory action and at
what stage of early pregnancy these antagonists are most effective.  To
define further the influence of these antagonists on the two components -
embryo and endometrium - embryo transfer experiments of treated embryos to
untreated pseudopregnant recipients and vice versa are proposed.  To
examine in more detail the physiological action of PAF on rabbit embryos,
other experiments to study phospholipid turnover, second messenger
generation and changes in intracellular calcium in response to PAF in
embryos of various stages of development are proposed.

Taken together, these experiments will define the role of PAF in the
implantation process in rabbits and elucidate whether it is actions on the
embryo or endometrium or both that are important for successful
implantation.  This information will be of importance for treatment of
infertility due to failure of blastocyst growth and development and
implantation, and for improving the success rate in patients requiring
treatment with assisted reproductive techn...

## Key facts

- **NIH application ID:** 2197062
- **Project number:** 5R01HD014048-14
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **SAM.gov UEI:** FXKMA43NTV21
- **Principal Investigator:** MICHAEL J. K. HARPER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $117,960
- **Award type:** 5
- **Project period:** 1980-04-01 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197062

## Citation

> US National Institutes of Health, RePORTER application 2197062, PROSTAGLANDINS & PAF IN ZYGOTE DEVELOPMENT & ATTACHMENT (5R01HD014048-14). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197062. Licensed CC0.

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