Skip to main content
Erschienen in: Journal of Assisted Reproduction and Genetics 5/2013

01.05.2013 | Gonadal Physiology and Disease

The role of genetic and autoimmune factors in premature ovarian failure

verfasst von: Nigyar N. Shamilova, Larisa A. Marchenko, Nataliya V. Dolgushina, Dmitry V. Zaletaev, Gennady T. Sukhikh

Erschienen in: Journal of Assisted Reproduction and Genetics | Ausgabe 5/2013

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To identify the role of both genetic (number of CGG repeats in the FMR1 gene) and autoimmune factors (anti-ovarian antibodies) in premature ovarian failure (POF).

Methods

In cross-sectional study, 78 women with POF were divided into 3 groups by the number of CGG repeats (less than 28, 28–36, more than 36) in any of the FMR1 gene alleles. We performed the detection of skewed X-chromosome inactivation, CGG repeats in the FMR1 gene, anti-ovarian antibodies (AOA) and sex hormones tests.

Results

Compared to a higher or lower number of CGG repeats the 28–36 triple CGG counts are strongly associated with the AOA detection (RR = 19.23, 95 % CI = 2.63–100.0). The women with autoimmune-driven POF have significantly higher anti-Mullerian hormone levels in comparison to women with non-autoimmune-driven POF.

Conclusion

The presence of AOA above 10 IU/mL is associated with the normal number of CGG repeats in regard to ovarian reserve and a better preservation of follicular primordial pool in the women with POF.
Literatur
1.
Zurück zum Zitat Allen RC, Zoghbi HY, Moseley AB, Rosenblatt HM, Belmont JW. Methylation of Hpa II and Hha I sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X-chromosome inactivation. Am J Hum Genet. 1992;51:1229–39.PubMed Allen RC, Zoghbi HY, Moseley AB, Rosenblatt HM, Belmont JW. Methylation of Hpa II and Hha I sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X-chromosome inactivation. Am J Hum Genet. 1992;51:1229–39.PubMed
2.
Zurück zum Zitat Allen EG, Sullivan AK, Marcus M, Small C, Dominguez C, Epstein MP, et al. Examination of reproductive aging milestones among women who carry the FMR1 premutation. Hum Reprod. 2007;22(8):2142–52.PubMedCrossRef Allen EG, Sullivan AK, Marcus M, Small C, Dominguez C, Epstein MP, et al. Examination of reproductive aging milestones among women who carry the FMR1 premutation. Hum Reprod. 2007;22(8):2142–52.PubMedCrossRef
3.
Zurück zum Zitat Ashrafi M, Fallahian M, Eshrati M, Yazdi RS. The Presence of Anti Thyroid and Anti Ovarian Auto-Antibodies in Familial Premature Ovarian Failure. Int J Fertil Steril. 2008;1(4):171–4. Ashrafi M, Fallahian M, Eshrati M, Yazdi RS. The Presence of Anti Thyroid and Anti Ovarian Auto-Antibodies in Familial Premature Ovarian Failure. Int J Fertil Steril. 2008;1(4):171–4.
4.
Zurück zum Zitat Chen LS, Tassone F, Sahota P, Hagerman PJ. The CGG repeat element within the 5′ untranslated region of the FMR1 message provides both positive and negative effects on in vivo translation of a downstream reporter. Hum Mol Genet. 2003;12(23):3067–74.PubMedCrossRef Chen LS, Tassone F, Sahota P, Hagerman PJ. The CGG repeat element within the 5′ untranslated region of the FMR1 message provides both positive and negative effects on in vivo translation of a downstream reporter. Hum Mol Genet. 2003;12(23):3067–74.PubMedCrossRef
5.
Zurück zum Zitat Conway GS, Katlas G, Patel A, Davies MS, Jacobs HS. Characterization of idiopathic premature ovarian failure. Fertil Steril. 1996;65(2):337–41.PubMed Conway GS, Katlas G, Patel A, Davies MS, Jacobs HS. Characterization of idiopathic premature ovarian failure. Fertil Steril. 1996;65(2):337–41.PubMed
6.
Zurück zum Zitat Conway GS, Payne NN, Webb J, Murray A, Jacobs PA. Fragile X premutation screening in women with premature ovarian failure. Hum Reprod. 1998;13(5):1184–7.PubMedCrossRef Conway GS, Payne NN, Webb J, Murray A, Jacobs PA. Fragile X premutation screening in women with premature ovarian failure. Hum Reprod. 1998;13(5):1184–7.PubMedCrossRef
7.
Zurück zum Zitat Coulam CB, Ryan RJ. Premature menopause.I. Etiology. Am J Obstet Gynecol. 1979;133(6):639–43.PubMed Coulam CB, Ryan RJ. Premature menopause.I. Etiology. Am J Obstet Gynecol. 1979;133(6):639–43.PubMed
8.
Zurück zum Zitat Fenishel P, Sosset C, Barbarino-Monnier P, Gobert B, Hieronimus S, Bene MC, et al. Prevalence, specificity and significance of antiovarian antibodies during spontaneous premature ovarian failure. Hum Reproad. 1997;12(12):2623–8.CrossRef Fenishel P, Sosset C, Barbarino-Monnier P, Gobert B, Hieronimus S, Bene MC, et al. Prevalence, specificity and significance of antiovarian antibodies during spontaneous premature ovarian failure. Hum Reproad. 1997;12(12):2623–8.CrossRef
9.
Zurück zum Zitat Fu YH, Kuhl DP, Pizzuti A, Pieretti M, Sutcliffe JS, Richards S, et al. Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell. 1991;67(6):1047–58.PubMedCrossRef Fu YH, Kuhl DP, Pizzuti A, Pieretti M, Sutcliffe JS, Richards S, et al. Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell. 1991;67(6):1047–58.PubMedCrossRef
10.
Zurück zum Zitat Gleicher N, Weghofer A, Barad D. Defining ovarian reserve to better understand ovarian aging. Reprod Biol Endocrinol. 2011;9:23.PubMedCrossRef Gleicher N, Weghofer A, Barad D. Defining ovarian reserve to better understand ovarian aging. Reprod Biol Endocrinol. 2011;9:23.PubMedCrossRef
11.
Zurück zum Zitat Gleicher N, Weghofer A, Barad DH. Ovarian reserve determinations suggest new function of FMR1 (fragile X gene) in regulating ovarian ageing. Reprod Biomed Online. 2010;20(6):768–75.PubMedCrossRef Gleicher N, Weghofer A, Barad DH. Ovarian reserve determinations suggest new function of FMR1 (fragile X gene) in regulating ovarian ageing. Reprod Biomed Online. 2010;20(6):768–75.PubMedCrossRef
12.
Zurück zum Zitat Gleicher N, Weghofer A, Oktay K, Barad D. Relevance of triple CGG repeats in the FMR1 gene to ovarian reserve. Reprod Biomed Online. 2009;19(3):385–90.PubMedCrossRef Gleicher N, Weghofer A, Oktay K, Barad D. Relevance of triple CGG repeats in the FMR1 gene to ovarian reserve. Reprod Biomed Online. 2009;19(3):385–90.PubMedCrossRef
13.
Zurück zum Zitat Gleicher N, Weghofer A, Oktay K, Barad DH. Is the immunological noise of abnormal autoimmunity an independent risk factor for premature ovarian aging? Menopause. 2009;16(4):760–4.PubMedCrossRef Gleicher N, Weghofer A, Oktay K, Barad DH. Is the immunological noise of abnormal autoimmunity an independent risk factor for premature ovarian aging? Menopause. 2009;16(4):760–4.PubMedCrossRef
14.
Zurück zum Zitat La Marka A, Marzotti S, Bronzetti A, Stabile G, Artenisio AC, Bini V, et al. Primary ovarian insufficiency due to steroidogenic cell autoimmunity is associated with a preserved pool of functioning follicles. J Clin Endocrinol Metab. 2009;94(10):3816–23.CrossRef La Marka A, Marzotti S, Bronzetti A, Stabile G, Artenisio AC, Bini V, et al. Primary ovarian insufficiency due to steroidogenic cell autoimmunity is associated with a preserved pool of functioning follicles. J Clin Endocrinol Metab. 2009;94(10):3816–23.CrossRef
15.
Zurück zum Zitat Sato K, Uehara S, Hashiyada M, Nabeshima H, Sugawara J, Terada Y, et al. Genetic significance of skewed X-chromosome inactivation in premature ovarian failure. Am J Med Genet. 2004;130A(3):240–4.PubMedCrossRef Sato K, Uehara S, Hashiyada M, Nabeshima H, Sugawara J, Terada Y, et al. Genetic significance of skewed X-chromosome inactivation in premature ovarian failure. Am J Med Genet. 2004;130A(3):240–4.PubMedCrossRef
16.
Zurück zum Zitat Shamilova NN, Marchenko LA, Shamilova NN, Marchenko LA. The FMR1 gene: new possibilities of assessing the ovarian reserve. Akusherstvo & Gynecologiya. 2011;2:58–64. article in Russian. Shamilova NN, Marchenko LA, Shamilova NN, Marchenko LA. The FMR1 gene: new possibilities of assessing the ovarian reserve. Akusherstvo & Gynecologiya. 2011;2:58–64. article in Russian.
17.
Zurück zum Zitat Sugawa F, Wada Y, Maruyama T, Uchida H, Ishizuka B, Ogata T. Premature ovarian failure and androgen receptor gene CAG repeat lengths weighted by X chromosome inactivation patterns. Fertil Steril. 2009;91(2):649–52.PubMedCrossRef Sugawa F, Wada Y, Maruyama T, Uchida H, Ishizuka B, Ogata T. Premature ovarian failure and androgen receptor gene CAG repeat lengths weighted by X chromosome inactivation patterns. Fertil Steril. 2009;91(2):649–52.PubMedCrossRef
18.
Zurück zum Zitat Sullivan AK, Marcus M, Epstein MP, Allen EG, Anido AE, Paquin JJ, et al. Association of FMR1 repeat size with ovarian dysfunction. Hum Reprod. 2005;20(2):402–12.PubMedCrossRef Sullivan AK, Marcus M, Epstein MP, Allen EG, Anido AE, Paquin JJ, et al. Association of FMR1 repeat size with ovarian dysfunction. Hum Reprod. 2005;20(2):402–12.PubMedCrossRef
19.
Zurück zum Zitat Tsigkou A, Marzotti S, Borges L, Brozzetti A, Reis F, Candeloro P, et al. High serum inhibin concentration discriminates autoimmune oophoritis from other forms of primary ovarian insufficiency. J Clin Endocrinol Metab. 2008;93(4):1263–9.PubMedCrossRef Tsigkou A, Marzotti S, Borges L, Brozzetti A, Reis F, Candeloro P, et al. High serum inhibin concentration discriminates autoimmune oophoritis from other forms of primary ovarian insufficiency. J Clin Endocrinol Metab. 2008;93(4):1263–9.PubMedCrossRef
20.
Zurück zum Zitat Welt CK. Primary ovarian insufficiency: a more accurate term for premature ovarian failure. Clin Endocrinol (Oxf). 2008;68(4):499–509.CrossRef Welt CK. Primary ovarian insufficiency: a more accurate term for premature ovarian failure. Clin Endocrinol (Oxf). 2008;68(4):499–509.CrossRef
21.
Zurück zum Zitat Wheatcroft NJ, Salt C, Milford-Ward A, Cooke ID, Weetman AP. Identification of ovarian antibodies by immunofluorescence, enzyme-linked immunosorbent assay or immunoblotting in premature ovarian failure. Hum Reprod. 1997;12(12):2617–22.PubMedCrossRef Wheatcroft NJ, Salt C, Milford-Ward A, Cooke ID, Weetman AP. Identification of ovarian antibodies by immunofluorescence, enzyme-linked immunosorbent assay or immunoblotting in premature ovarian failure. Hum Reprod. 1997;12(12):2617–22.PubMedCrossRef
22.
Zurück zum Zitat Wittenberger MD, Hagerman RJ, Sherman SL, McConkie-Rosell A, Welt CK, Rebar RW, et al. The FMR1 premutation and reproduction. Fertil Steril. 2007;87(3):456–65.PubMedCrossRef Wittenberger MD, Hagerman RJ, Sherman SL, McConkie-Rosell A, Welt CK, Rebar RW, et al. The FMR1 premutation and reproduction. Fertil Steril. 2007;87(3):456–65.PubMedCrossRef
Metadaten
Titel
The role of genetic and autoimmune factors in premature ovarian failure
verfasst von
Nigyar N. Shamilova
Larisa A. Marchenko
Nataliya V. Dolgushina
Dmitry V. Zaletaev
Gennady T. Sukhikh
Publikationsdatum
01.05.2013
Verlag
Springer US
Erschienen in
Journal of Assisted Reproduction and Genetics / Ausgabe 5/2013
Print ISSN: 1058-0468
Elektronische ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-013-9974-4

Weitere Artikel der Ausgabe 5/2013

Journal of Assisted Reproduction and Genetics 5/2013 Zur Ausgabe

Ambulantisierung: Erste Erfahrungen mit dem Hybrid-DRG

02.05.2024 DCK 2024 Kongressbericht

Die Hybrid-DRG-Verordnung soll dazu führen, dass mehr chirurgische Eingriffe ambulant durchgeführt werden, wie es in anderen Ländern schon länger üblich ist. Die gleiche Vergütung im ambulanten und stationären Sektor hatten Niedergelassene schon lange gefordert. Aber die Umsetzung bereitet ihnen doch Kopfzerbrechen.

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

Harninkontinenz: Netz-Op. erfordert über lange Zeit intensive Nachsorge

30.04.2024 Harninkontinenz Nachrichten

Frauen mit Belastungsinkontinenz oder Organprolaps sind nach einer Netz-Operation keineswegs beschwerdefrei. Vielmehr scheint die Krankheitslast weiterhin hoch zu sein, sogar höher als von harninkontinenten Frauen, die sich nicht haben operieren lassen.

Welche Übungen helfen gegen Diastase recti abdominis?

30.04.2024 Schwangerenvorsorge Nachrichten

Die Autorinnen und Autoren einer aktuellen Studie aus Griechenland sind sich einig, dass Bewegungstherapie, einschließlich Übungen zur Stärkung der Bauchmuskulatur und zur Stabilisierung des Rumpfes, eine Diastase recti abdominis postpartum wirksam reduzieren kann. Doch vieles ist noch nicht eindeutig belegt.

Update Gynäkologie

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