title: Do alterations in follicular fluid proteases contribute to human infertility?
abstract: OBJECTIVE
  Cathepsin L and ADAMTS-1 are known to play critical roles in follicular rupture, ovulation, and fertility in mice. Similar studies in humans are limited; however, both are known to increase during the periovulatory period. No studies have examined either protease in the follicular fluid of women with unexplained infertility or infertility related to advanced maternal age (AMA). We sought to determine if alterations in cathepsin L and/or ADAMTS-1 existed in these infertile populations.
  
  
  METHODS
  Patients undergoing in vitro fertilization (IVF) for unexplained infertility or AMA-related infertility were prospectively recruited for the study; patients with tubal or male factor infertility were recruited as controls. Follicular fluid was collected to determine gene expression (via quantitative polymerase chain reaction), enzyme concentrations (via enzyme-linked immunosorbent assays), and enzymatic activities (via fluorogenic enzyme cleavage assay or Western blot analysis) of cathepsin L and ADAMTS-1.
  
  
  RESULTS
  The analysis included a total of 42 patients (14 per group). We found no statistically significant difference in gene expression, enzyme concentration, or enzymatic activity of cathepsin L or ADAMTS-1 in unexplained infertility or AMA-related infertility as compared to controls. We also found no statistically significant difference in expression or concentration with advancing age.
  
  
  CONCLUSIONS
  Cathepsin L and ADAMTS-1 are not altered in women with unexplained infertility or AMA-related infertility undergoing IVF, and they do not decline with advancing age. It is possible that differences exist in natural cycles, contributing to infertility; however, our findings do not support a role for protease alterations as a common cause of infertility.
authors: Department of Obstetrics & Gynecology, Division of Reproductive Endocrinology & Infertility, University of Iowa College of Medicine, 200 Hawkins Drive, Iowa City, IA, 52242, USA, lisa-cookingham@uiowa.edu.
authors: Lisa Marii
authors: LM
authors: Cookingham
authors: Bradley J
authors: BJ
authors: Van Voorhis
authors: Mario
authors: M
authors: Ascoli
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000071097:ADAMTS1 Protein; D000328:Adult; D000818:Animals; D015153:Blotting, Western; D016022:Case-Control Studies; D056668:Cathepsin L / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005307:Fertilization in Vitro; D015571:Follicular Fluid / Q000737:chemistry / Q000201:enzymology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007246:Infertility / Q000175:diagnosis* / Q000201:enzymology*; D008297:Male; D008423:Maternal Age; D051379:Mice; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; C534281:CTSL protein, human; D056668:Cathepsin L; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human