Regulation and function of the human fallopian tube
Author: Wånggren, Kjell
Date: 2007-06-01
Location: Skandiasalen, Astrid Lindgrens Barnsjukhus, Karolinska Universitetssjukhuset, Solna
Time: 09.00
Department: Institutionen för kvinnors och barns hälsa / Department of Women's and Children's Health
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thesis.pdf (1.814Mb)
Abstract
The Fallopian tube is essential for human reproduction. Transport of the
spermatozoa, the egg, and later the pre-embryo is believed to be aided by
muscular contractions in the wall of the Fallopian tube and cilia in the
mucosa. An optimal environment in the Fallopian tube is of importance for
fertilization of the egg and development of the pre-embryo. Progesterone
(P) and prostaglandins (PG) are important regulators of reproductive
processes. Leukemia Inhibitory Factor (LIF) is an important cytokine
involved in embryo development and endometrialreceptivity. The function
of the Fallopian tube and its correlation to fertility is still not fully
investigated.
The aims of the studies were to investigate (i) the uptake of intra-abdominal particles into the Fallopian tube, (ii) the transport of particles from the pouch of Douglas to the cervical mucus, (iii) the effect of hormones on the muscular contractions in the Fallopian tube, (iv) the presence of receptors for PGE2 and PGF2alpha in the human Fallopian tube and how they are regulated by hormones, and (v) the presence of receptors for LIF and gp130, and their regulation by P in the human Fallopian tube and the endometrium, as well as their localization in the pre-implantation embryo.
Healthy volunteers and patients undergoing surgery for benign causes or legal sterilization were included in the studies. All subjects were of fertile age and had regular menstrual cycles. Using gamma camera imaging and autoradiography we found evidence for uptake of radio labelled particles in the Fallopian tube after intra abdominal deposition. In-vitro contractility studies of longitudinal strips of the Fallopian tube showed different effects of hormones and drugs on muscular contractions. P, mifepristone, PGE1, levonorgestrel, human chorionic gonadotrophin (hCG), and oxytocin decreased, whereas PGF2 and PGE2 increased the contractions.
Immunohistochemistry (IHC), confocal microscopy, reverse transcriptase PCR, and real time PCR were used to detect and confirm the expression of PGE and PGF2alpha receptors, and c-kit in the Fallopian tube. The PG receptors were mainly expressed in the apical part of the luminal epithelial cells, in the muscular wall, and in the vessels. Treatment with mifepristone reduced the staining. IHC showed staining of LIF receptor (LIFR) and gp130 protein in the Fallopian tube, the endometrium, and pre-implantation embryos. LIFR was mainly seen in the apical and basolateral parts of the luminal epithelial cells, in the muscular wall, and vessels. The staining for gp130 was weak. Real time PCR showed expression of mRNA for LIFR and gp130 in the Fallopian tube and the endometrium. In the pre-implantation embryo, LIFR staining was seen in all cells, at all stages. Gp130 was present in all cells up to the morula stage, but only in the inner cell mass of the blastocyst.
In conclusion: Uptake of particles in the Fallopian tube suggests a retrograde transport mechanism. Muscular contractions in the Fallopian tube are regulated by PG and P. PG receptors are expressed in the human Fallopian tube and regulated by P. LIFR and gp130 are expressed in the human Fallopian tube, the endometrium, and the pre-implantation embryo. The pattern of LIFR expression indicates that LIFR is likely to be of importance for communication between the embryo and the Fallopian tube.
The aims of the studies were to investigate (i) the uptake of intra-abdominal particles into the Fallopian tube, (ii) the transport of particles from the pouch of Douglas to the cervical mucus, (iii) the effect of hormones on the muscular contractions in the Fallopian tube, (iv) the presence of receptors for PGE2 and PGF2alpha in the human Fallopian tube and how they are regulated by hormones, and (v) the presence of receptors for LIF and gp130, and their regulation by P in the human Fallopian tube and the endometrium, as well as their localization in the pre-implantation embryo.
Healthy volunteers and patients undergoing surgery for benign causes or legal sterilization were included in the studies. All subjects were of fertile age and had regular menstrual cycles. Using gamma camera imaging and autoradiography we found evidence for uptake of radio labelled particles in the Fallopian tube after intra abdominal deposition. In-vitro contractility studies of longitudinal strips of the Fallopian tube showed different effects of hormones and drugs on muscular contractions. P, mifepristone, PGE1, levonorgestrel, human chorionic gonadotrophin (hCG), and oxytocin decreased, whereas PGF2 and PGE2 increased the contractions.
Immunohistochemistry (IHC), confocal microscopy, reverse transcriptase PCR, and real time PCR were used to detect and confirm the expression of PGE and PGF2alpha receptors, and c-kit in the Fallopian tube. The PG receptors were mainly expressed in the apical part of the luminal epithelial cells, in the muscular wall, and in the vessels. Treatment with mifepristone reduced the staining. IHC showed staining of LIF receptor (LIFR) and gp130 protein in the Fallopian tube, the endometrium, and pre-implantation embryos. LIFR was mainly seen in the apical and basolateral parts of the luminal epithelial cells, in the muscular wall, and vessels. The staining for gp130 was weak. Real time PCR showed expression of mRNA for LIFR and gp130 in the Fallopian tube and the endometrium. In the pre-implantation embryo, LIFR staining was seen in all cells, at all stages. Gp130 was present in all cells up to the morula stage, but only in the inner cell mass of the blastocyst.
In conclusion: Uptake of particles in the Fallopian tube suggests a retrograde transport mechanism. Muscular contractions in the Fallopian tube are regulated by PG and P. PG receptors are expressed in the human Fallopian tube and regulated by P. LIFR and gp130 are expressed in the human Fallopian tube, the endometrium, and the pre-implantation embryo. The pattern of LIFR expression indicates that LIFR is likely to be of importance for communication between the embryo and the Fallopian tube.
List of papers:
I. Lundberg S, Wanggren K, Almstrom H, Lundberg HJ, Asard PE, Wramsby H (2005). "Detection of Tc-99m labelled albumin particles in the Fallopian tubes after intraperitoneal deposition." Eur J Obstet Gynecol Reprod Biol 119(2): 210-4
Pubmed
II. Wanggren K, Lundberg S, Lundberg HJ, Asard PE, Wramsby H (2003). "Radioactivity in cervical mucus after intraperitoneal deposition of Tc-99m labelled albumin particles before and after sterilisation." Eur J Obstet Gynecol Reprod Biol 108(2): 203-8
Pubmed
III. Wanggren K, Stavreus-Evers A, Andersson E , Gemzell-Danielsson K (2007). "Regulation of muscular contractions in the human Fallopian tube through Prostaglandins and Progestins." (Manuscript)
IV. Wanggren K, Lalitkumar PG, Stavreus-Evers A, Stabi B, Gemzell-Danielsson K (2006). "Prostaglandin E2 and F2alpha receptors in the human Fallopian tube before and after mifepristone treatment." Mol Hum Reprod 12(9): 577-85. Epub 2006 Jul 4
Pubmed
V. Wanggren K, Lalitkumar PG, Hambiliki F, Stabi B, Gemzell-Danielsson K, Stavreus-Evers A (2007). "Leukaemia inhibitory factor receptor and gp130 in the human Fallopian tube and endometrium before and after mifepristone treatment and in the human preimplantation embryo." Mol Hum Reprod Apr 12: Epub ahead of print
Pubmed
I. Lundberg S, Wanggren K, Almstrom H, Lundberg HJ, Asard PE, Wramsby H (2005). "Detection of Tc-99m labelled albumin particles in the Fallopian tubes after intraperitoneal deposition." Eur J Obstet Gynecol Reprod Biol 119(2): 210-4
Pubmed
II. Wanggren K, Lundberg S, Lundberg HJ, Asard PE, Wramsby H (2003). "Radioactivity in cervical mucus after intraperitoneal deposition of Tc-99m labelled albumin particles before and after sterilisation." Eur J Obstet Gynecol Reprod Biol 108(2): 203-8
Pubmed
III. Wanggren K, Stavreus-Evers A, Andersson E , Gemzell-Danielsson K (2007). "Regulation of muscular contractions in the human Fallopian tube through Prostaglandins and Progestins." (Manuscript)
IV. Wanggren K, Lalitkumar PG, Stavreus-Evers A, Stabi B, Gemzell-Danielsson K (2006). "Prostaglandin E2 and F2alpha receptors in the human Fallopian tube before and after mifepristone treatment." Mol Hum Reprod 12(9): 577-85. Epub 2006 Jul 4
Pubmed
V. Wanggren K, Lalitkumar PG, Hambiliki F, Stabi B, Gemzell-Danielsson K, Stavreus-Evers A (2007). "Leukaemia inhibitory factor receptor and gp130 in the human Fallopian tube and endometrium before and after mifepristone treatment and in the human preimplantation embryo." Mol Hum Reprod Apr 12: Epub ahead of print
Pubmed
Issue date: 2007-05-11
Rights:
Publication year: 2007
ISBN: 978-91-7357-159-3
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