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Am J Transl Res 2012;4(3):269-278
Review Article
The role of estrogen in the pathophysiology of tubal ectopic pregnancy
Ruijin Shao, Yi Feng, Shien Zou, Birgitta Weijdegård, Gencheng Wu, Mats Brännström, Håkan Billig
Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy,
University of Gothenburg, Gothenburg 40530, Sweden; Department of Integrative Medicine and Neurobiology,
State Key Lab of Medical Neurobiology, Shanghai Medical College and Institute of Acupuncture Research (WHO
Collaborating Center for Traditional Medicine), Institute of Brain Science, Fudan University, Shanghai 200032,
China; Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011,
China; Department of Obstetrics and Gynecology, The Sahlgrenska Academy, University of Gothenburg,
Gothenburg 41345, Sweden
Received June 3, 2012; accepted June 25, 2012; Epub July 20, 2012; Published August 15, 2012
Abstract: 17β-estradiol, acting through estrogen receptors α and β, plays a fundamental role in the regulation of
Fallopian tube cell homeostasis and in the modulation of normal tubal physiological processes. Fluctuations in
E2 levels also play crucial roles in the initiation or progression of numerous human diseases. Fallopian tube
malfunction often results in tubal ectopic pregnancy, which is one cause of maternal morbidity and mortality in
women. Several factors have been proposed to be associated with increased risk of tubal ectopic pregnancy, but
whether these factors are the cause of, or are merely symptoms of, such pregnancies remains unresolved due to
the lack of knowledge in regards to the mechanisms by which embryos inadvertently implant in the Fallopian
tube. This review summarizes recent findings, including data from our own laboratory, on E2 metabolism and
estrogen receptor (ER) subtype expression within the Fallopian tube in humans and rodents. This review also
outlines several important, unresolved questions in the field that, once addressed, could offer important clues
into how E2/ER signaling contributes to the pathology of tubal function. A better understanding of the specific
functions of estrogen receptor subtypes in vivo, as well as of the mechanism and consequences of receptor
subtype interactions is critical to understanding their respective roles in Fallopian tube physiology and in the
pathophysiology and etiology of tubal ectopic pregnancy. (AJTR1206002).
Keywords: 17β-estradiol, estrogen receptor subtypes, human, infertility, tubal ectopic pregnancy
Address all correspondence to:
Dr. Ruijin Shao
Department of Physiology/Endocrinology
Institute of Neuroscience and Physiology
The Sahlgrenska Academy
University of Gothenburg, Gothenburg 40530, Sweden.
Tel: +46 31 7863408; Fax: +46 31 7863512
E-mail: ruijin.shao@fysiologi.gu.se
Review Article
The role of estrogen in the pathophysiology of tubal ectopic pregnancy
Ruijin Shao, Yi Feng, Shien Zou, Birgitta Weijdegård, Gencheng Wu, Mats Brännström, Håkan Billig
Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy,
University of Gothenburg, Gothenburg 40530, Sweden; Department of Integrative Medicine and Neurobiology,
State Key Lab of Medical Neurobiology, Shanghai Medical College and Institute of Acupuncture Research (WHO
Collaborating Center for Traditional Medicine), Institute of Brain Science, Fudan University, Shanghai 200032,
China; Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011,
China; Department of Obstetrics and Gynecology, The Sahlgrenska Academy, University of Gothenburg,
Gothenburg 41345, Sweden
Received June 3, 2012; accepted June 25, 2012; Epub July 20, 2012; Published August 15, 2012
Abstract: 17β-estradiol, acting through estrogen receptors α and β, plays a fundamental role in the regulation of
Fallopian tube cell homeostasis and in the modulation of normal tubal physiological processes. Fluctuations in
E2 levels also play crucial roles in the initiation or progression of numerous human diseases. Fallopian tube
malfunction often results in tubal ectopic pregnancy, which is one cause of maternal morbidity and mortality in
women. Several factors have been proposed to be associated with increased risk of tubal ectopic pregnancy, but
whether these factors are the cause of, or are merely symptoms of, such pregnancies remains unresolved due to
the lack of knowledge in regards to the mechanisms by which embryos inadvertently implant in the Fallopian
tube. This review summarizes recent findings, including data from our own laboratory, on E2 metabolism and
estrogen receptor (ER) subtype expression within the Fallopian tube in humans and rodents. This review also
outlines several important, unresolved questions in the field that, once addressed, could offer important clues
into how E2/ER signaling contributes to the pathology of tubal function. A better understanding of the specific
functions of estrogen receptor subtypes in vivo, as well as of the mechanism and consequences of receptor
subtype interactions is critical to understanding their respective roles in Fallopian tube physiology and in the
pathophysiology and etiology of tubal ectopic pregnancy. (AJTR1206002).
Keywords: 17β-estradiol, estrogen receptor subtypes, human, infertility, tubal ectopic pregnancy
Address all correspondence to:
Dr. Ruijin Shao
Department of Physiology/Endocrinology
Institute of Neuroscience and Physiology
The Sahlgrenska Academy
University of Gothenburg, Gothenburg 40530, Sweden.
Tel: +46 31 7863408; Fax: +46 31 7863512
E-mail: ruijin.shao@fysiologi.gu.se
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