Systemic hormonal modulation induces sperm nucleosomal imbalance in rat spermatozoa.

Sperm chromatin packaging is a very complex and highly regulated phenomenon. While most of the sperm chromatin is replaced by protamines, some are retained in nucleosomes. It is recently being recognised that these nucleosomes are intentionally retained and could be contributing to the expression of genes in the very early stages of embryogenesis.

Endocrine control of epigenetic mechanisms in male reproduction.

Endocrine control of reproduction is very well known and has been echoed by many research groups. However, recent developments point to the ability of toxic endocrine disrupting chemicals (EDC) to alter epigenetic information of the gametes which gets transferred to the developing embryo and affects the immediate reproductive outcome or even persists transgenerationally. These epigenetic aberrations contribute to the ensuing pathophysiology of reproductive disorders.

Aberrant methylation of multiple imprinted genes in embryos of tamoxifen-treated male rats.

Genomic imprinting is an epigenetic phenomenon known to regulate fetal growth and development. Studies from our laboratory have demonstrated that treatment of adult male rats with tamoxifen increased postimplantation loss around mid gestation. Further studies demonstrated the aberrant expression of transcripts of several imprinted genes in the resorbing embryos at days 11 and 13 of gestation including IGF2.

Methylation status of imprinted genes DLK1-GTL2, MEST (PEG1), ZAC (PLAGL1), and LINE-1 elements in spermatozoa of normozoospermic men, unlike H19 imprinting control regions, is not associated with idiopathic recurrent spontaneous miscarriages.

Objective: To study methylation aberrations in spermatozoa at developmentally important imprinted regions to ascertain their role in early embryo loss in idiopathic recurrent spontaneous miscarriages (RSM).

Design: Case-control study.

Setting: Academic research setting at National Institute for Research in Reproductive Health, Parel, Mumbai.

Methylation analysis of idiopathic recurrent spontaneous miscarriage cases reveals aberrant imprinting at H19 ICR in normozoospermic individuals.

Objective: To study H19 ICR methylation levels in association with sperm parameters routinely analyzed in idiopathic recurrent spontaneous miscarriage cases.

Design: Case-control study.

Setting: Academic research setting.

Potential role of estrogen in regulation of the insulin-like growth factor2-H19 locus in the rat testis.

The selective estrogen receptor modulator, tamoxifen, has been shown to reduce DNA methylation at Insulin-like growth factor 2/H19 differentially methylated region (Igf2/H19 DMR) in the spermatozoa of the Holtzman rats. Since imprint at this locus is acquired during spermatogenesis in the male germ-line, we hypothesized role for estrogen signaling in the methylation dynamics in the testis. The present study was designed to identify putative estrogen response elements (ERE) at Igf2/H19 DMR and their interaction with DNA methylation pathway.