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  

Oleh:

Pathak, Shilpa ; Kedia-Mokashi, Neelam ; Saxena, Madhurima ; D'Souza, Ryan

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Fertility and Sterility (keterangan: ada di ClinicalKey) vol. 91 no. 5 Sup (May 2009), page 2253-2263.
Topik: Tamoxifen; estrogen; DNA methylation; genomic imprinting; imprinting control region; embryo development

Ketersediaan

Perpustakaan FK Nomor Panggil: F02.K.2009.02 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

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.

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