Induction of developmental anomalies in mice by maternal stress

Abstract

The short-time restraint of pregnant mice on day 8 of gestation led to a significant increase of the anomaly rate in fetuses. This effect may be due to stress factors of endocrine origin.

Effects of restraint stress in gestation: Implications for rodent developmental toxicology studies

“…In addition to standard tube, taping, and wire mesh restraints, confinement in an apparatus used to deliver radiation dosing to pregnant mice has been studied (Michel and Fritz‐Niggli, 1978). Following up on previous observations made during radiation experiments, the investigators used durations of 1.8, 10, 20, and 36 min on gd 8 and looked at abnormal fetuses (intrauterine growth retardation and external malformations) on gd 13.…”

“…However, the details of this early experiment were not well described. The shortest effective restraint periods reported were <40 min (Michel and Fritz‐Niggli, 1978). The restraint method in the experiment was unique, a radiation exposure chamber described as allowing “no free movements.” Another difference from more standard restraint experiments was an examination of the fetuses on gd 13 rather than at term.…”

“…The more recent studies of restraint during organogenesis measured and reported birth/fetal weights, but did not find effects of restraint (Rojo et al, 1985,1986; Beyer and Chernoff, 1986; Chernoff et al, 1988; Gutierrez et al, 1989; Tyl et al, 1994; Colomina et al, 1995,1997,1998,1999a,1999b,2001; Miller and Chernoff, 1995; Albina et al, 2002; Torrente et al, 2002). Individual studies reported an increased incidence of growth retardation in gd13 fetuses (Michel and Fritz‐Niggli, 1978), lower intrauterine as well as postnatal growth in male offspring of rat dams restrained on gd 18–20 (Barlow et al, 1978), and decreased mean newborn weight per litter after plastic tube restraint of rats before and during gestation (Glöckner and Karge, 1991). Using late gestation restraint+light paradigm (see Endpoints Affected by Restraint: Postnatal Survival, Growth, and Sex Differentiation), reduced birth weights were found in some studies (Williams et al, 1998; Stohr et al, 1998), but not others (Holson et al, 1995).…”

“…Notably, restraint periods used in late gestation, when restricted food intake during the restraint would be more likely to impact rapid fetal growth, are typically shorter than those used during organogenesis. Other characteristics of the studies that may be relevant are the embryonic, rather than fetal, evaluation of growth retardation (Michel and Fritz‐Niggli, 1978), the longer restraint including preconception period (Glöckner and Karge, 1991), and the induction of altered gestation length by the restraint (Barlow et al, 1978), as well as details of the restraint procedures.…”

Effect of Maternal Restraint Stress on Fetal Development of ICR Mice

“…It has been reported that maternal stress causes growth retardation, cleft palate or resorption of fetuses in rodents [3,20,32]. Increased production of glucocorticoids during maternal stress mediating embryo-fetal toxicities including cleft palate and skeletal malformations has been proposed as a possible mechanism [4][5][6]21], and has been demonstrated that excess exposure to glucocorticoids retards fetal growth in animals and humans [22,25,30,34].…”