Rapid effects of progesterone on ciliary beat frequency in the mouse fallopian tube

Abstract

BackgroundThe physiological regulation of ciliary beat frequency (CBF) within the fallopian tube is important for controlling the transport of gametes and the fertilized ovum. Progesterone influences gamete transport in the fallopian tube of several mammalian species. In fallopian tubes isolated from cows, treatment with 20 micromolar progesterone caused a rapid reduction of the tubal CBF. The aims of this study were to establish methodology for studying fallopian tube CBF in the mouse, as it is an important model species, and to investigate if progesterone rapidly affects the CBF of mice at nM concentrations.MethodsA method to assess tubal CBF of mice was developed. Fallopian tubes were dissected and the tissue was cut in small pieces. Tissue samples with moving cilia were located under an inverted bright field microscope and held still against the bottom of a petri dish by a motorized needle system. Images were acquired over 90 minutes at 35 degrees C with a high-speed camera and used for assessing changes in the CBF in response to the addition of hormone.ResultsThe baseline CBF of the mouse fallopian tube was 23.3 +/- 3.8 Hz. The CBF was stable over at least 90 minutes allowing establishment of a baseline frequency, addition of hormone and subsequent recordings. Progesterone at concentrations of 20 micromolar and 100 nM significantly reduced the CBF by 10% and 15% respectively after 30 minutes compared with controls.ConclusionsThe present study demonstrates that the mouse, despite its small size, is a useful model for studying the fallopian tube CBF ex vivo. The rapid reduction in CBF by 100 nM progesterone suggests that gamete transport in the fallopian tube could be mediated by progesterone via a non-genomic receptor mechanism.

Sex Hormone–Dependent Regulation of Cilia Beat Frequency in Airway Epithelium

“…In the oviduct, CBF was depressed by approximately 50% in the presence of P4 concentrations similar to those that we used (15,25,26). In contrast to a rapid, nongenomic mechanism described in oviduct epithelium, where specific interactions of sperm and ovum are required (36,38), we found that the inhibition in the airway epithelium and reversal was slow (24 h), suggesting that P4 transcriptionally reprograms the cell to regulate CBF. This was supported by the ability of actinomycin D to completely block the effect of P4 without diminishing PR expression, although further studies will be required to confirm transcriptional mechanisms.…”

“…Temporal features of P4-mediated inhibition of CBF in mouse and human fallopian tube suggest that both nongenomic and genomic mechanisms are at play (36). However, in airway epithelia, the relatively slow onset of inhibition of CBF and delayed reversal of the P4 effect (24 h) supports a genomic response.…”

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

“…Considering that the effect of progesterone on ciliated cells is very rapid, it has been suggested that these effects are part of the non-genomic actions of progesterone [49].…”

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.…”

“…P 4 and E 2 are the key players in regulating ciliary beat frequency (CBF). P 4 reduces CBF through classical progesterone receptors (PGRs) expressed on the ciliated epithelial cells in a dosage-dependent manner in humans and mice (Mahmood et al 1998, Bylander et al 2010, 2013. A non-classical PGR is expressed in the lower part of the cilia stalk in mouse oviducts (Teilmann et al 2006).…”