Skip to main content
Erschienen in: Journal of Assisted Reproduction and Genetics 5/2015

01.05.2015 | Reproductive Physiology and Disease

Do alterations in follicular fluid proteases contribute to human infertility?

verfasst von: Lisa Marii Cookingham, Bradley J. Van Voorhis, Mario Ascoli

Erschienen in: Journal of Assisted Reproduction and Genetics | Ausgabe 5/2015

Einloggen, um Zugang zu erhalten

Abstract

Purpose

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.
Literatur
1.
Zurück zum Zitat Schochet SS. A suggestion as to the process of ovulation and ovarian cyst formation. A preliminary report. Anat Rec. 1916;10:447–57.CrossRef Schochet SS. A suggestion as to the process of ovulation and ovarian cyst formation. A preliminary report. Anat Rec. 1916;10:447–57.CrossRef
2.
Zurück zum Zitat Robker RL, Russell DL, Espey LL, Lydon JP, O’Malley BW, Richards JS. Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases. Proc Natl Acad Sci U S A. 2000;97:4689–94.CrossRefPubMedCentralPubMed Robker RL, Russell DL, Espey LL, Lydon JP, O’Malley BW, Richards JS. Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases. Proc Natl Acad Sci U S A. 2000;97:4689–94.CrossRefPubMedCentralPubMed
3.
Zurück zum Zitat Brown HM, Dunning KR, Robker RL, Boerboom D, Pritchard M, Lane M, et al. ADAMTS1 cleavage of Versican mediates essential structural remodeling of the ovarian follicle and cumulus-oocyte matrix during ovulation in mice. Biol Reprod. 2010;83:549–57.CrossRefPubMed Brown HM, Dunning KR, Robker RL, Boerboom D, Pritchard M, Lane M, et al. ADAMTS1 cleavage of Versican mediates essential structural remodeling of the ovarian follicle and cumulus-oocyte matrix during ovulation in mice. Biol Reprod. 2010;83:549–57.CrossRefPubMed
5.
Zurück zum Zitat García V, Kohen P, Maldonado C, Sierralta W, Muñoz A, Villarroel C, et al. Transient expression of progesterone receptor and cathepsin-l in human granulosa cells during the periovulatory period. Fertil Steril. 2012;97:707–13.CrossRefPubMed García V, Kohen P, Maldonado C, Sierralta W, Muñoz A, Villarroel C, et al. Transient expression of progesterone receptor and cathepsin-l in human granulosa cells during the periovulatory period. Fertil Steril. 2012;97:707–13.CrossRefPubMed
6.
Zurück zum Zitat Yung Y, Maman E, Konopnicki S, Cohen B, Brengauz M, Lojkin I, et al. ADAMTS-1: a new human ovulatory gene and a cumulus marker for fertilization capacity. Mol Cell Endocrinol. 2010;328:104–8.CrossRefPubMed Yung Y, Maman E, Konopnicki S, Cohen B, Brengauz M, Lojkin I, et al. ADAMTS-1: a new human ovulatory gene and a cumulus marker for fertilization capacity. Mol Cell Endocrinol. 2010;328:104–8.CrossRefPubMed
7.
Zurück zum Zitat Freimann S, Ben-Ami I, Dantes A, Armon L, Ben Ya’cov-Klein A, Ron-El R, et al. Differential expression of genes coding for EGF-like factors and ADAMTS1 following gonadotropin stimulation in normal and transformed human granulosa cells. Biochem Biophys Res Commun. 2005;333:935–43.CrossRefPubMed Freimann S, Ben-Ami I, Dantes A, Armon L, Ben Ya’cov-Klein A, Ron-El R, et al. Differential expression of genes coding for EGF-like factors and ADAMTS1 following gonadotropin stimulation in normal and transformed human granulosa cells. Biochem Biophys Res Commun. 2005;333:935–43.CrossRefPubMed
8.
Zurück zum Zitat Xiao S, Yubin L, Li T, Chen M, Xu Y, Wen Y, et al. Evidence for decreased expression of ADAMTS-1 associated with impaired oocyte quality in PCOS patients. JCEM. 2014;99:E1015–21.PubMed Xiao S, Yubin L, Li T, Chen M, Xu Y, Wen Y, et al. Evidence for decreased expression of ADAMTS-1 associated with impaired oocyte quality in PCOS patients. JCEM. 2014;99:E1015–21.PubMed
9.
Zurück zum Zitat Practice Committee of the American Society for Reproductive Medicine. Effectiveness and treatment for unexplained infertility. Fertil Steril. 2006;86:S111–4. Practice Committee of the American Society for Reproductive Medicine. Effectiveness and treatment for unexplained infertility. Fertil Steril. 2006;86:S111–4.
10.
Zurück zum Zitat Qublan H, Amarin Z, Nawasreh M, Diab F, Malkawi S, Al-Ahmad N, et al. Luteinized unruptured follicle syndrome: incidence and recurrence rate in infertility women with unexplained infertility undergoing intrauterine insemination. Hum Reprod. 2006;21:2110–3.CrossRefPubMed Qublan H, Amarin Z, Nawasreh M, Diab F, Malkawi S, Al-Ahmad N, et al. Luteinized unruptured follicle syndrome: incidence and recurrence rate in infertility women with unexplained infertility undergoing intrauterine insemination. Hum Reprod. 2006;21:2110–3.CrossRefPubMed
11.
Zurück zum Zitat Vollman RF. The menstrual cycle. In: Friedman E, editor. Major Problems in Obstetrics and Gynecology. Philadelphia: W.B. Saunders; 1977. p. 1–193. Vollman RF. The menstrual cycle. In: Friedman E, editor. Major Problems in Obstetrics and Gynecology. Philadelphia: W.B. Saunders; 1977. p. 1–193.
12.
Zurück zum Zitat Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3:1101–8.CrossRefPubMed Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3:1101–8.CrossRefPubMed
13.
Zurück zum Zitat Russell DL, Doyle KM, Ochsner SA, Sandy JD, Richards JS. Processing and localization of ADAMTS-1 and proteolytic cleavage of versican during cumulus matrix expansion and ovulation. J Biol Chem. 2003;278:42330–9.CrossRefPubMed Russell DL, Doyle KM, Ochsner SA, Sandy JD, Richards JS. Processing and localization of ADAMTS-1 and proteolytic cleavage of versican during cumulus matrix expansion and ovulation. J Biol Chem. 2003;278:42330–9.CrossRefPubMed
14.
Zurück zum Zitat Sriraman V, Richards JS. Cathepsin L gene expression and promoter activation in rodent granulosa cells. Endocrinology. 2004;145:582–91.CrossRefPubMed Sriraman V, Richards JS. Cathepsin L gene expression and promoter activation in rodent granulosa cells. Endocrinology. 2004;145:582–91.CrossRefPubMed
15.
Zurück zum Zitat Jansen E, Laven JS, Dommerholt HB, Polman J, van Rijt C, van den Hurk C, et al. Abnormal gene expression profiles in human ovaries from polycystic ovary syndrome patients. Mol Endocrinol. 2004;18:3050–63.CrossRefPubMed Jansen E, Laven JS, Dommerholt HB, Polman J, van Rijt C, van den Hurk C, et al. Abnormal gene expression profiles in human ovaries from polycystic ovary syndrome patients. Mol Endocrinol. 2004;18:3050–63.CrossRefPubMed
Metadaten
Titel
Do alterations in follicular fluid proteases contribute to human infertility?
verfasst von
Lisa Marii Cookingham
Bradley J. Van Voorhis
Mario Ascoli
Publikationsdatum
01.05.2015
Verlag
Springer US
Erschienen in
Journal of Assisted Reproduction and Genetics / Ausgabe 5/2015
Print ISSN: 1058-0468
Elektronische ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-015-0447-9

Weitere Artikel der Ausgabe 5/2015

Journal of Assisted Reproduction and Genetics 5/2015 Zur Ausgabe

Hirsutismus bei PCOS: Laser- und Lichttherapien helfen

26.04.2024 Hirsutismus Nachrichten

Laser- und Lichtbehandlungen können bei Frauen mit polyzystischem Ovarialsyndrom (PCOS) den übermäßigen Haarwuchs verringern und das Wohlbefinden verbessern – bei alleiniger Anwendung oder in Kombination mit Medikamenten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Weniger postpartale Depressionen nach Esketamin-Einmalgabe

Bislang gibt es kein Medikament zur Prävention von Wochenbettdepressionen. Das Injektionsanästhetikum Esketamin könnte womöglich diese Lücke füllen.

Bei RSV-Impfung vor 60. Lebensjahr über Off-Label-Gebrauch aufklären!

22.04.2024 DGIM 2024 Kongressbericht

Durch die Häufung nach der COVID-19-Pandemie sind Infektionen mit dem Respiratorischen Synzytial-Virus (RSV) in den Fokus gerückt. Fachgesellschaften empfehlen eine Impfung inzwischen nicht nur für Säuglinge und Kleinkinder.

Update Gynäkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.