The classical progesterone receptor mediates the rapid reduction of fallopian tube ciliary beat frequency by progesterone

Abstract

BackgroundThe transport of gametes as well as the zygote is facilitated by motile cilia lining the inside of the fallopian tube. Progesterone reduces the ciliary beat frequency within 30 minutes in both cows and mice. This rapid reduction suggest the involvement of a non-genomic signaling mechanism, although it is not known which receptors that are involved. Here we investigated the possible involvement of the classical progesterone receptor in this process.MethodThe ciliary beat frequency of mice fallopian tube was measured ex vivo using an inverted bright field microscope and a high speed camera. The effects of the agonists progesterone and promegestone and an antagonist, mifeprestone, were investigated in wildtype mice. The effect of progesterone was also investigated in mice lacking the classical progesterone receptor.ResultsProgesterone, as well as the more specific PR agonist promegestone, significantly reduced the CBF at concentrations of 10–100 nanomolar within 10–30 minutes. In the absence of progesterone, the PR antagonist mifeprestone had no effect on the ciliary beat frequency at a concentration of 1 micromolar. When ciliated cells were pre-incubated with 1 micromolar mifeprestone, addition of progesterone did not reduce the ciliary beat frequency. Accordingly, in ciliated cells from mice not expressing the classical progesterone receptor, exposure to 100 nanomolar progesterone did not reduce the ciliary beat frequency.ConclusionsThis is the first study to provide comprehensive evidence that the classical progesterone receptor mediates the rapid reduction of the tubal ciliary beat frequency by progesterone.

Motile cilia harbor serum response factor as a mechanism of environment sensing and injury response in the airway

“…Additionally, progesterone receptors have been found on the motile cilia of oviduct epithelium and play a role in quickly responding to progesterone in the milieu (8,43). In fact, it has recently been found that in sea urchins the hedgehog signaling receptor Smoothened is located on motile cilia during development and motile cilia are required for hedgehog signaling (42), although no connection has been made to motile cilia in modulating signal transduction via transcription factor regulation at the cilia.…”

“…However, recent studies have revealed a surprising compilation of unexpected receptors on motile cilia, as well as evidence that motile cilia do indeed act as sensory organelles by harboring mechanoreceptive and chemoreceptive capacities, as reviewed by Bloodgood in 2010 (6). These sensory functions include the localization of bitter receptors on ciliated airway epithelium that regulate sensing and expelling of noxious substances in the milieu, and the expression of progesterone receptors on cilia in oviduct epithelium that assist in sensing and modulating cilia beat frequency (CBF) during the estrous cycle (8,36,40,43). Furthermore, the Smoothened, FGFR1, and VANGL2 membrane protein receptors have been found to be localized to motile cilia and play roles in development in various different model systems (16,31,42).…”

Tubal transport of gametes and embryos: a review of physiology and pathophysiology

“…Both classic (cytoplasmic) progesterone receptors [50], as well as membrane-bound progesterone receptor gamma [51] have been implicated to be involved in signal transduction to ciliated cells.…”

Oviduct: roles in fertilization and early embryo development

“…A non-classical PGR is expressed in the lower part of the cilia stalk in mouse oviducts (Teilmann et al 2006). Recent studies in mice indicated that low dosage of P 4 and short activation time (within 30 min) are sufficient to reduce oviductal CBF (Bylander et al 2010(Bylander et al , 2013. Therefore, extra-nuclear signaling of CBF through nongenomic actions of P 4 without involving a long-delayed genomic regulation may be the cause of direct CBF regulation.…”