Genome-wide assessment of DNA methylation alterations induced by superovulation, sexual immaturity and in vitro follicle growth in mouse blastocysts

In their attempt to fulfill the wish of having children, women who suffer from fertility issues often undergo assisted reproductive technologies (ART) such as ovarian stimulation, which has been associated with adverse health outcomes and imprinting disorders in children. However, given the crucial role of exogenous hormone stimulation in improving human infertility treatments, a more comprehensive analysis of the potential impacts on DNA methylation in embryos following ovarian stimulation is needed. Here, we provide genome-wide DNA methylation profiles of blastocysts generated after superovulation of prepubertal or adult mice, compared with blastocysts derived from non-stimulated adult mice. Additionally, we assessed the impact of the in vitro growth and maturation of oocytes on methylation in blastocysts. Overall design: Mouse blastocysts (F1xF1; C57BL/6JxCBACa) derived from oocytes obtained after superovulation of adult (SOa; 8-10 week) and prepubertal (SOp; 23 days) mice compared with blastocysts produced with naturally ovulated oocytes (NO) from adult mice. All zygotes were subject to the same in vitro culture conditions. Hatched blastocysts were collected on day 5 of in vitro culture. Additionally, in a separete group of blastocysts the oocytes were collected at primordial or early pre-antral stages and subjected to in vitro follicule culture maturation process. All samples were processed for library generation to assess whole-genome DNA methylation profile.