Abnormal Development at Early Postimplantation Stage in Mouse Embryos After Preimplantation Genetic Diagnosis

Abstract

Preimplantation genetic diagnosis (PGD) is an established procedure for the genetic analysis of embryos. To assess the effect of the procedure on early embryonic development, we generated a murine experimental system, including mice implanted with biopsied in vitro cultured embryos, control mice implanted with in vitro cultured embryos without biopsy, and mice with naturally conceived embryos. Embryos at the 7.5-dpc stage were isolated from all three groups and the embryo implantation rate, the survival rate of implanted embryos, and the developmental stage of surviving embryos were carefully assessed and compared among all three groups. We found the implantation rate was similar between biopsied and control group embryos (67.92% vs. 66.67%). However, the survival rate of implanted embryos in the biopsied group (49.31%) was significantly lower than that of the control (60.91%) and normal groups (96.24%) at 7.5 dpc. In addition, the survival rate of control group embryos was significant lower than that of normal group embryos. Classification of the precise developmental stages of randomly selected live implanted embryos at 7.5 dpc revealed no differences among the three groups. Our results indicate that blastomere biopsy does not adversely affect embryo implantation. The PGD procedure, in particular blastomere biopsy, increases the rate of embryo death at 4.5-7.5 dpc, but does not affect the development of surviving 7.5 dpc embryos.

Embryo biopsy and development: the known and the unknown

“…A gross morphological evaluation of developing mouse fetuses obtained following BB did not show delayed development in early pregnancy (7.5 dpc, Yang et al 2012), while reduced fetal, but not placental, weight was observed starting from 12.5 dpc (Sato et al 2014, Yao et al 2016. Of relevance, a low fetal/placental weight ratio was observed in BB conceptuses, suggesting increased risk of cardiovascular diseases later in life (Thornburg et al 2010).…”

“…Though the majority of studies did not show an increased incidence of pregnancy complications following embryo biopsy, some reported that BB is associated with reduced implantation rates, increased risks of low birth weight or preterm birth (Banerjee et al 2008, Thomaidis et al 2012, Cimadomo et al 2016 and, in early childhood, with impaired cognitive and/or motor development (Banerjee et al 2008, Middelburg et al 2011, Thomaidis et al 2012, Cimadomo et al 2016, while no indication on TB pregnancy/babies are available. Research on mouse model has shown that BB is not only associated with increased pregnancy loss and reduced/delayed fetal development, but also with impaired placental functions and epigenetic defects in both fetuses and placentae (Sugawara et al 2012, Yang et al 2012, Sato et al 2014, Wu et al 2014, Yao et al 2016. Regarding TB, research on mouse model is very limited so far.…”

“…Studies to assess epigenetic, behavioral, reproductive and/or metabolic health in the pre-or postnatal life following TB have not been published so far, while few research groups have performed studies to assess BB risk(s) and safety (Yu et al 2009, 2013, Sugawara et al 2012, Yang et al 2012, Zeng et al 2013, Sampino et al 2014, Sato et al 2014, Wu et al 2014. Thus, in the following sections, we will focus our attention on BB, rather than TB.…”