Front Matter

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.)