Embryonic mortality and intrauterine growth retardation (IUGR) associated with placental alterations in pregnant rats treated with methyl methanesulfonate (MMS) at the peri-implantation stage

Abstract

-Embryonic mortality and intrauterine growth retardation (IUGR) are induced by exposure of rodents to xenobiotic agents during the pregastrulation period of development. We examined the time course of the effects of methyl methanesulfonate (MMS), an alkylating agent, on conceptus development in order to clarify the relative roles of the embryo and the placenta in their induction. Pregnant rats were treated orally with a single dose of MMS (200 mg/kg) in the morning of gestation day (GD) 6 (peri-implantation stage). Embryonic mortality was increased on GD12 and thereafter by MMS treatment, with newly dead embryos showing placental hypoplasia at GD12. Embryo or fetal weight was also smaller for MMS-treated dams than for control dams from GD14 to GD20. The labyrinth zone and junctional zone (JZ) of the placenta were thinner in MMS-treated rats from GD12 to GD17 and from GD12 to GD20 (except for GD17), respectively. Furthermore, MMS-treated dams showed a smaller number of glycogen cells in the JZ on GD14. In contrast, the placental glycogen concentration was higher and the expression of glucose transporter 1 in the JZ remained at GD20. These results indicate that exposure of pregnant rats to MMS at the peri-implantation stage of embryogenesis affects placental development and growth. The placental impairment induced by MMS was likely responsible for the embryonic death observed 6 days after exposure of dams to this agent as well as for the IUGR of surviving embryos or fetuses throughout the gestation period.

Effects of restricted feeding on fetal and placental development in pregnant rabbits

“…In the histological examination of the placenta, the labyrinth zone was signifi cantly thinner and the basal zone was signifi cantly thicker in the RF group than in the NT group. An abnormally thin labyrinth zone is a common fi nding of intrauterine growth retardation in rats (Yokoi et al, 2008) and rabbits (Zhang et al, 1995), and a decreased placental surface area with decreased numbers of end villi is said to be related to decreased transport of nutrition to the fetus, resulting in fetal growth inhibition (Constância et al, 2002, Zygmunt et al, 2003Olausson et al, 2003). It is known that in the placenta of rabbits, PAS-positive glycogen-containing cells in the basal zone almost disappear during the late gestational period.…”

Histomorphological comparison of rat placentas by different timing of chlorpromazine-administration

“…A strong relationship has been observed between placental weight and fetal weight in human . It has been reported that some toxicants induce small placenta and IUGR with embryonic/fetal death or malformations in rodents, such as busulfan (Furukawa et al, 2007), 5-azacytidine (Vlahović et al, 1999), methyl methanesulfonate (Yokoi et al, 2008), ethylnitrosourea (Katayama et al, 2002), 1-␤-d-arabinofuranosylcytosine (Yamauchi et al, 2003), etc. Although impairment in the developmental of placental vessels leads to impaired fetal growth, the placenta can withstand functional inactivation (Sankaran and Kyle, 2009).…”