TY - JOUR
T1 - Cyclic activity of signal transduction pathways in fimbrial epithelium of the human fallopian tube
AU - van der Ploeg, P.
AU - Uittenboogaard, A.
AU - Bucks, K.M.M.
AU - Lentjes-Beer, M.H.F.M.
AU - Bosch, S.L.
AU - van Rumste, M.M.E.
AU - Vos, M.C.
AU - van Diest, P.J.
AU - Lambrechts, S.
AU - van de Stolpe, A.
AU - Bekkers, R.L.M.
AU - Piek, J.M.J.
N1 - Funding Information:
Phyllis van der Ploeg is an employee of the Catharina Hospital, where her research work is funded by the Catharina Research fund and Molecular Pathway. Dx, Philips. Anja van de Stolpe is an employee of Molecular Pathway Dx, Philips. The other authors declare no conflict of interest.
Funding Information:
This study was partly funded by the Catharina Research fund and Molecular Pathway Dx, Philips. The Catharina Research fund had no role in the study design, data collection, analysis and interpretation or writing of the manuscript. Molecular Pathway Dx, Philips was involved in the study design, analysis and interpretation of data and reviewing of the manuscript.
Publisher Copyright:
© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).
PY - 2022/2
Y1 - 2022/2
N2 - Introduction The local environment of the fallopian tube represents the optimal conditions for reproductive processes. To maintain tissue homeostasis, signal transduction pathways are thought to play a pivotal role. Enhancing our understanding of functional signal transduction pathway activity is important to be able to clarify the role of aberrant signal transduction pathway activity leading to female subfertility and other tubal diseases. Therefore, in this study we investigate the influence of the hormonal cycle on the activity of key signal transduction pathways in the fimbrial epithelium of morphologically normal fallopian tubes. Material and methods We included healthy pre- (n = 17) and postmenopausal (n = 8) patients who had surgical interventions for benign gynecologic conditions. Histologic sections of the fallopian tubes were reviewed by two pathologists and, for the premenopausal patients, hormone serum levels and sections of the endometrium were examined to determine the hormonal phase (early follicular [n = 4], late follicular [n = 3], early luteal [n = 5], late luteal [n = 5]). After laser capture microdissection, total mRNA was extracted from the fimbrial epithelium and real-time quantitative reverse transcription-PCR was performed to determine functional signal transduction pathway activity of the androgen receptor (AR), estrogen receptor (ER), phosphoinositide-3-kinase (PI3K), Hedgehog (HH), transforming growth factor-beta (TGF-beta) and canonical wingless-type MMTV integration site (Wnt) pathways. Results The early luteal phase demonstrated high AR and ER pathway activity in comparison with the late luteal phase (p = 0.016 and p = 0.032, respectively) and low PI3K activity compared with the late follicular phase (p = 0.036), whereas the late luteal phase showed low activity of HH and Wnt compared with the early follicular phase (both p = 0.016). Signal transduction pathway activity in fimbrial epithelium from postmenopausal patients was most similar to the early follicular and/or late luteal phase with regard to the AR, ER and PI3K pathways. Wnt pathway activity in postmenopausal patients was comparable to the late follicular and early luteal phase. We observed no differences in HH and TGF-beta pathway activity between pre- and postmenopausal samples. The cyclic changes in signal transduction pathway activity suggest a stage-specific function which may affect the morphology and physiology of the human fallopian tube. Conclusions We demonstrated cyclic changes in activity of the AR, ER, PI3K, HH and Wnt pathways throughout the hormonal cycle.
AB - Introduction The local environment of the fallopian tube represents the optimal conditions for reproductive processes. To maintain tissue homeostasis, signal transduction pathways are thought to play a pivotal role. Enhancing our understanding of functional signal transduction pathway activity is important to be able to clarify the role of aberrant signal transduction pathway activity leading to female subfertility and other tubal diseases. Therefore, in this study we investigate the influence of the hormonal cycle on the activity of key signal transduction pathways in the fimbrial epithelium of morphologically normal fallopian tubes. Material and methods We included healthy pre- (n = 17) and postmenopausal (n = 8) patients who had surgical interventions for benign gynecologic conditions. Histologic sections of the fallopian tubes were reviewed by two pathologists and, for the premenopausal patients, hormone serum levels and sections of the endometrium were examined to determine the hormonal phase (early follicular [n = 4], late follicular [n = 3], early luteal [n = 5], late luteal [n = 5]). After laser capture microdissection, total mRNA was extracted from the fimbrial epithelium and real-time quantitative reverse transcription-PCR was performed to determine functional signal transduction pathway activity of the androgen receptor (AR), estrogen receptor (ER), phosphoinositide-3-kinase (PI3K), Hedgehog (HH), transforming growth factor-beta (TGF-beta) and canonical wingless-type MMTV integration site (Wnt) pathways. Results The early luteal phase demonstrated high AR and ER pathway activity in comparison with the late luteal phase (p = 0.016 and p = 0.032, respectively) and low PI3K activity compared with the late follicular phase (p = 0.036), whereas the late luteal phase showed low activity of HH and Wnt compared with the early follicular phase (both p = 0.016). Signal transduction pathway activity in fimbrial epithelium from postmenopausal patients was most similar to the early follicular and/or late luteal phase with regard to the AR, ER and PI3K pathways. Wnt pathway activity in postmenopausal patients was comparable to the late follicular and early luteal phase. We observed no differences in HH and TGF-beta pathway activity between pre- and postmenopausal samples. The cyclic changes in signal transduction pathway activity suggest a stage-specific function which may affect the morphology and physiology of the human fallopian tube. Conclusions We demonstrated cyclic changes in activity of the AR, ER, PI3K, HH and Wnt pathways throughout the hormonal cycle.
KW - computational models
KW - fimbriae
KW - hormonal cycle
KW - human fallopian tube
KW - signal transduction pathways
KW - CELL HEIGHT
KW - EXPRESSION
KW - CILIATION
KW - ESTROGEN
KW - OVIDUCT
U2 - 10.1111/aogs.14306
DO - 10.1111/aogs.14306
M3 - Article
C2 - 34927235
SN - 0001-6349
VL - 101
SP - 256
EP - 264
JO - Acta Obstetricia et Gynecologica Scandinavica
JF - Acta Obstetricia et Gynecologica Scandinavica
IS - 2
ER -