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Fertil Steril. 2009 May;91(5 Suppl):2253-63. doi: 10.1016/j.fertnstert.2008.07.1709. Epub 2008 Sep 7.

Effect of tamoxifen treatment on global and insulin-like growth factor 2-H19 locus-specific DNA methylation in rat spermatozoa and its association with embryo loss.

Author information

1
National Institute for Research in Reproductive Health, Indian Council for Medical Research, Mumbai, India.

Abstract

OBJECTIVE:

To determine the effect of tamoxifen treatment on global and insulin-like growth factor 2-H19 imprinting control region (Igf2-H19 ICR)-specific DNA methylation in rat spermatozoa and analyze its association with postimplantation loss.

DESIGN:

Experimental prospective study.

SETTING:

Animal research and academic research facility.

SUBJECT(S):

Male and female 75-day-old Holtzman rats.

INTERVENTION(S):

Global and Igf2-H19 ICR-specific DNA methylation was analyzed in an epididymal sperm sample in control and tamoxifen-treated rats at a dose of 0.4 mg tamoxifen/kg/day. DNA methylation status was correlated to postimplantation loss in females mated with tamoxifen-treated males.

MAIN OUTCOME MEASURE(S):

Global sperm DNA methylation level, methylation status of Igf2-H19 ICR in sperm, postimplantation loss.

RESULT(S):

Tamoxifen treatment significantly reduced methylation at Igf2-H19 ICR in epididymal sperm. However, the global methylation level was not altered. A mating experiment confirmed a significant increase in postimplantation loss upon tamoxifen treatment and showed significant correlation with methylation at Igf2-H19 ICR.

CONCLUSION(S):

Reduced DNA methylation at Igf2-H19 ICR in rat spermatozoa upon tamoxifen treatment indicated a role of estrogen-associated signaling in the acquisition of paternal-specific imprints during spermatogenesis. In addition, association between DNA methylation and postimplantation loss suggests that errors in paternal imprints at Igf2-H19 ICR could affect embryo development.

[Indexed for MEDLINE]

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