100 Oxytocin, Arginine Vasopressin and Autism Spectrum Disorder
and postnatal day 14. To extrapolate the effects of pharmacologic and environ-
mental manipulation of the oxytocin–oxytocin receptor system in the human
newborn brain from experiments performed in mice and rats, treatments
should thus be performed in rodents around postnatal day 10, when a compa-
rable maturation of the brain and of the oxytocin receptor system has been
reached in these species. Most importantly, we show that synthetic fragrances
and many of the ingredients commonly found in many fragrances [i.e., diethyl
phthalate (DEP), tonalide (musk ketone), octinoxate, d‐limonene, eugenol,
benzyl benzoate, benzyl salicylate, (+)‐ α‐pinene] reduce the number of
oxytocin receptor positive neurons in male neuroblastoma cell lines. We will
provide detailed information below, but at this point it is suffice to mention
that if an exposed offspring is born with significantly low numbers of oxytocin
receptor expressing neurons, then delivery of a large amount of oxytocin may
not be as effective since the “synthetic chemicals” have already damaged the
corresponding receptors (see below for more detail).
Several environmental factors have been reported to affect oxytocin receptor
expressions in embryogenesis and the neonatal period, with social and
Oxytocin receptor developmental expression
First appearance ofOXR in the brain
Embryonic
day 14
Embryonic
day 18
Prenatal day 10
Prenatal day 13
Infant pattern
Caudate nucleus
Nucleus accumens Bed nucleus of thestria terminalis
Hypothalamus ventro-
medial nucleus
PN-Postnatal
Periform
cortex Lateral septum
Gestational
week 5
Gestational
week 8 Prenatal day 10Prenatal day 13
Amygdala
Anterior
Transient OXR expression
Dorsal
Olfactory
Adult pattern
Prenatal
Age day 19
Progressive appearance of OXRin discrete brain regime First transition to theadult pattern Second transition tothe adult pattern
Permanent OXR expression
(a)
(b)
Figure 4.1 Developmental trajectories of oxytocin receptor in the rat brain. (a) Schematic
time course of oxytocin receptor expression in the developing brain. (b) Oxytocin receptor
expression in the infant brain around prenatal period P10–P13. Regions in which a transient
oxytocin receptor expression is observed are colored in red. Regions in which oxytocin
receptor expression is maintained to adult life are colored in blue. OXR, oxytocin receptor.
Source: Ref. [10]. Copyright (c) 2015 Grinevich et al. (See insert for color representation of
this figure.)