title: Small-conductance, calcium-activated potassium channel 3 (SK3) is a modulator of endometrial remodeling during endometrial growth.
abstract: BACKGROUND
  Small-conductance, Ca(2+)-activated K(+) channel 3 (SK3) has been shown to be expressed in porcine endometrium. However, the roles of SK3 in human endometrium during the menstrual cycle and early pregnancy are unknown.
  
  
  OBJECTIVE
  The objective of the study was to investigate the expression and function of SK3 in human endometrium and the mechanism involved.
  
  
  METHODS
  We determined the expression of SK3 in human endometrium by RT-PCR, Western blotting, and immunofluorescence. Using electrophysiological and fluorescent imaging techniques, we investigated the effects of SK3 on the membrane potential and the concentrations of cytosolic calcium, respectively. The effects of SK3 on endometrial thickness and pregnancy outcome were also investigated. Knockdown of endometrial SK3 was used to examine the effects of SK3 on cell migration, cytoskeleton formation, and calcium concentration in the cytosol.
  
  
  RESULTS
  SK3 channels are present in human endometrium. In vivo experimental and clinical data demonstrated that the reduced expression of SK3 was associated with a thin endometrium and unsuccessful pregnancy outcomes. Knockdown of human endometrial SK3 attenuated the rise in cytosolic calcium and membrane hyperpolarization induced by thapsigargin, a Ca(2+)-ATPase inhibitor, cell migration, and F-actin assembly. Knockdown of endometrial SK3 in mice also resulted in a thin endometrium and unsuccessful pregnancy outcome.
  
  
  CONCLUSIONS
  These observations demonstrate that SK3 channels are expressed in human endometrial cells. Reduced SK3 expression attenuates endometrial cell migration and is associated with unsuccessful pregnancy outcomes.
authors: The Key Laboratory of Reproductive Genetics (Y.-C.L., J.Y., G.-L.D., S.S., D.Z., L.J., J.-X.P., X.-H.L., Y.-M.Z., J.-Z.S., H.-F.H.), Ministry of Education (Zhejiang University), Department of Reproductive Endocrinology (Y.-C.L., J.Y., G.-L.D., D.Z., L.J., J.-X.P., X.-H.L., Y.-M.Z., H.-F.H.), Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China; Department of Pathology and Pathophysiology (S.S., J.-Z.S.), School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China; and International Peace Maternity and Child Health Hospital (H.-F.H.), Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
authors: Yong-Chao
authors: YC
authors: Lu
authors: Jing
authors: J
authors: Yang
authors: Guo-Lian
authors: GL
authors: Ding
authors: Shuai
authors: S
authors: Shi
authors: Dan
authors: D
authors: Zhang
authors: Li
authors: L
authors: Jin
authors: Jie-Xue
authors: JX
authors: Pan
authors: Xian-Hua
authors: XH
authors: Lin
authors: Yi-Min
authors: YM
authors: Zhu
authors: Jian-Zhong
authors: JZ
authors: Sheng
authors: He-Feng
authors: HF
authors: Huang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D004717:Endometrium / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro; D055785:Gene Knockdown Techniques; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D008597:Menstrual Cycle / Q000235:genetics / Q000378:metabolism*; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011256:Pregnancy Outcome; D061251:Primary Cell Culture; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*; D020554:Sperm Injections, Intracytoplasmic
chemical_list: C496894:KCNN1 protein, human; C496897:KCNN2 protein, human; C406328:KCNN3 protein, human; C496895:Kcnn1 protein, mouse; C496898:Kcnn2 protein, mouse; C496900:Kcnn3 protein, mouse; D051640:Small-Conductance Calcium-Activated Potassium Channels; D002118:Calcium