Progesterone-mediated effects on gene expression and oocyte-cumulus complex transport in the mouse fallopian tube.

Anna Bylander,Lina Gunnarsson,Ruijin Shao,Dg Joakim Larsson,Håkan Billig

doi:10.1186/s12958-015-0038-8

Anna Bylander, Lina Gunnarsson + Show 3 more

Open Access

https://doi.org/10.1186/s12958-015-0038-8

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Abstract

BackgroundThe fallopian tube transports the gametes to the fertilization site and delivers the embryo to the uterus at the optimal time for implantation. Progesterone and the classical progesterone receptor are involved in regulating both tubal ciliary beating and muscular contractions, likely via both genomic and non-genomic actions.MethodsTo provide more details of the underlying mechanisms, we investigated the effect of progesterone on gene expression in mice fallopian tubes in vitro at 20 min, 2 h and 8 h post progesterone treatment using microarray and/or quantitative PCR. In parallel, oocyte cumulus complex transport was investigated in ovulating mice that were injected with one of the progesterone receptor antagonists, Org 31710 or CDB2194.ResultsMicroarray analyses did not reveal any apparently regulated genes 20 min after progesterone treatment, consistent with the proposed non-genomic action of progesterone controlling ciliary beating. After 2 h, 11 genes were identified as up-regulated. Analyses using quantitative PCR at 2 h and 8 h showed a consistent up-regulation of endothelin1 and a down-regulation of its receptor Endothelin receptor A by progesterone. We also confirmed that treatment with progesterone receptor antagonists before ovulation accelerates the transport of the oocyte cumulus complex.ConclusionsThis is the first study showing that progesterone regulates the expression of endothelin1 and endothelin receptor A in the fallopian tube. Together with previous studies of the effects of endothelin on muscular contractions in the fallopian tube, the results from this study suggest that endothelin is a mediator of the progesterone-controlled effects on muscular contraction and eventually gamete transport in the fallopian tube.Electronic supplementary materialThe online version of this article (doi:10.1186/s12958-015-0038-8) contains supplementary material, which is available to authorized users.

Highlights

The fallopian tube transports the gametes to the fertilization site and delivers the embryo to the uterus at the optimal time for implantation
For mice treated with CDB2194, a similar significant decrease in the ratio of mice with oocyte cumulus complex (OCC) present was found at 27 h (p = 0.007) and 30 h (p = 0.0008) after human chorionic gonadotropin (hCG) injection
To identify possible progesterone-dependent genes involved in gamete transport and in rapid reduction of ciliary beat frequency (CBF), we performed a microarray analysis on fallopian tubes isolated from mice and exposed in vitro to 100 nmol/L progesterone for 20 min and 2 h

Summary

Introduction

The fallopian tube transports the gametes to the fertilization site and delivers the embryo to the uterus at the optimal time for implantation. Prostaglandins seem to have a dual effect on contractility where the E-series (PGE) relaxes muscle activity and the F-series (PGF) induces muscle activity This response appears to be influenced by ovarian steroids, as progesterone increases the response to PGE1 and decreases the response to PGF2alpha [16]. One in vitro study by Wanggren et al demonstrated the effects of 100 nM progesterone on muscle contractions in the fallopian tube within 20 min [9]. Such a rapid time course supports the hypothesis that progesterone regulates muscular activity through both transcriptional and non-transcriptional pathways. Progesterone and RU486 was administered at the same time and at equal concentrations, which may not be sufficient for efficient blockage [18, 19]

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