Estrogen-induced abnormally high cystic fibrosis transmembrane conductance regulator expression results in ovarian hyperstimulation syndrome.
Ovarian hyperstimulation syndrome (OHSS) remains one of the most life-threatening and potentially fatal complications of assisted reproduction treatments, arising from excessive stimulation of the ovaries by exogenous gonadotropins administrated during in vitro fertilization procedures, which is characterized by massive fluid shift and accumulation in the peritoneal cavity and other organs, including the lungs and the reproductive tract. The pathogenesis of OHSS remains obscure, and no definitive treatments are currently available. Using RT-PCR, Western blot, and electrophysiological techniques we show that cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel expressed in many epithelia, is involved in the pathogenesis of OHSS. Upon ovarian hyperstimulation, rats develop OHSS symptoms, with up-regulated CFTR expression and enhanced CFTR channel activity, which can also be mimicked by administration of estrogen, but not progesterone, alone in ovariectomized rats. Administration of progesterone that suppresses CFTR expression or antiserum against CFTR to OHSS animals results in alleviation of the symptoms. Furthermore, ovarian hyperstimulation does not induce detectable OHSS symptoms in CFTR mutant mice. These findings confirm a critical role of CFTR in the pathogenesis of OHSS and may provide grounds for better assisted reproduction treatment strategy to reduce the risk of OHSS and improve in vitro fertilization outcome.
Ajonuma
Louis Chukwuemeka
LC
Epithelial Cell Biology Research Center, Department of Physiology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, New Territory, Hong Kong.
Tsang
Lai Ling
LL
Zhang
Gui Hong
GH
Wong
Connie Hau Yan
CH
Lau
Miu Ching
MC
Ho
Lok Sze
LS
Rowlands
Dewi Kenneth
DK
Zhou
Chen Xi
CX
Ng
Chuen Pei
CP
Chen
Jie
J
Xu
Peng Hui
PH
Zhu
Jin Xia
JX
Chung
Yiu Wa
YW
Chan
Hsiao Chang
HC
D000818:Animals; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism* / Q000633:toxicity; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007106:Immune Sera / Q000494:pharmacology; D051379:Mice; D008817:Mice, Mutant Strains; D016471:Ovarian Hyperstimulation Syndrome / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000235:genetics
D004967:Estrogens; D007106:Immune Sera; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D011374:Progesterone