Evidence of prokineticin dysregulation in fallopian tube from women with ectopic pregnancy.
OBJECTIVE
To demonstrate expression and regulation of prokineticins (PROKs) and their receptors (PROKRs) in fallopian tube (FT) from women who are not pregnant and women with ectopic pregnancy (EP).


METHODS
Tissue analysis.


METHODS
Large United Kingdom teaching hospital.


METHODS
Women undergoing hysterectomy for benign gynecological conditions (n = 15) and surgery for EP (n = 16).


METHODS
Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry were used to determine FT PROK/PROKR messenger RNA (mRNA) expression and protein localization, respectively. The PROK/PROKR levels were measured in tubal explant cultures stimulated with estrogen (E) and progestogen.


METHODS
Differential expression of PROK and PROKR.


RESULTS
The FT PROK2 and PROKR1 mRNA levels were up-regulated during the P-dominant midluteal phase of the menstrual cycle. Increased PROKR1 expression was observed in tubal explant cultures treated with medroxy-progesterone acetate (MPA). The PROK and PROKR proteins were localized to the epithelium and smooth muscle layers of the FT. The PROKR1 and PROKR2 mRNA levels were lower in FT from women with EP compared with nonpregnant FT from the midluteal phase.


CONCLUSIONS
These data suggest a potential role for PROKs in FT function. The PROKs are known to affect smooth muscle contraction in the gut. Dysregulated PROK expression in FT could affect FT smooth muscle contractility and embryo-tubal transport, providing a potential cause for EP.
Shaw
Julie L V
JL
Centre for Reproductive Biology, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
Denison
Fiona C
FC
Evans
Jemma
J
Durno
Kimberley
K
Williams
Alistair R
AR
Entrican
Gary
G
Critchley
Hilary O D
HO
Jabbour
Henry N
HN
Horne
Andrew W
AW
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D003271:Contraceptive Agents, Female / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism; D005187:Fallopian Tubes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D008875:Middle Aged; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D011247:Pregnancy; D011271:Pregnancy, Ectopic / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / Q000378:metabolism*; D055815:Young Adult
D003271:Contraceptive Agents, Female; D005768:Gastrointestinal Hormones; D009479:Neuropeptides; C467610:PROK1 protein, human; C423608:PROK2 protein, human; C470837:PROKR1 protein, human; C470838:PROKR2 protein, human; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived; D017258:Medroxyprogesterone Acetate