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Prenatal exposure to maternal

depression, neonatal methylation


of human glucocorticoid receptor
gene (NR3C1) and infant cortisol
stress responses

University of British Columbia; Vancouver


Epigenetics
Impact factor: 4,77
NO COMPARABLES
Modelo animal

Diferencia en la rta Mas atencin


Mala atencin
al estrs en materna Vs Menos
materna
descendencia atencin materna

Expresin de GR en
McComick: Exn 1-7
hipocampo:
Weaver: Metilacin
Rotacin serotonina
en NGFI-A
central
Estudio
La exposicin prenatal al estado de animo
depresivo/ansioso de la madre se asocia con
METILACION de 1F-NR3C1?

Se metila su homologo en ratas NGFI-A?


Caractersticas de las madres
MEDIDAS

- HAM-A 26 Semanas, 33 semanas, 3 meses

- HAM-D 26 Semanas, 33 semanas, 3 meses

- EPDS 26 Semanas, 33 semanas, 3 meses

- PSI-SF Medida de estrs parental


Caractersticas de los nios
.
Metodologa
TOMA DE MUESTRA

Materna- Mediados de tercer semestre


Neonatal- Venosa
Sangre del cordn.
Saliva
Metodologa
TECNICAS PARA DETERMINAR ESTADO DE METILACIN.

- LINE- 1: Metilacin global PyroMark LINE-1


- Regiones ricas en CpG del NR3C1 incluido el exn 1F-
Bisulfite pyrosequencing

CONVERSIN POR BISULFITO- EpiTect (Qiagen)

Amplificacin por PCR -3492 a -3082

REACCION DE PCR- HotStar (Qiagen)

SECUENCIACIN: PyroMark
13 sitios CpG
CpG 3 y 4, potencial
sitio de unin NGFI-A
Homologa a la regin 1-
7 de la rata
Figure 2. Methylation levels (%) at each of the 13
CpG sites analyzed in exon 1F of NR3C1 in maternal
(Fig. 2A) and newborns (Fig. 2B) (expo- sure group
means SEM). Prenatal exposure to SRIs did not
influence the methylation status of NR3C1 CpG sites
(all differences between groups ps > 0.05). (C)
Neonatal LINE-1 methylation (% SEM) status and
prenatal exposure. LINE-1 methylation levels did not
vary between SRI exposed and non-exposed infants
(p > 0.05) even when accounting for prenatal maternal
mood (Fig. 2C). LINE-1 methylation levels in newborns
were not associated with basal or stress cortisol levels
in infants at three months (p > 0.05).
Figure 3. Associations between exposure to
prenatal maternal mood as assessed during the
second and third trimesters and newborn NR3C1
methylation status. Increased second trimester
EPDS symptom scores, controlling for SRI
exposure, were associated with increased
neonatal methylation levels at CpG2 ( = 0.286; t
= 2.216; p = 0.031, 2 = 0.075) (A). At midthird
trimester, again controlling for SRI use, HAM-A
and HAM-D scores were positively associated with
methylation status at CpG1 ( =.312, t=2.614, p =
0.011, 2 = 0.081 and =.317, t = 2.602, p =
0.011, 2 = 0.081, respectively) (B). Similarly,
EPDS, HAM-D and HAM-A scores (third trimester)
were positively associated with increased levels of
CpG2 methylation ( = 0.305, t = 2.651; p = 0.010;
2 = 0.084; = 0.371, t = 3.082, p = 0.003; 2 =
0.110; and = 0.363, t = 3.080, p = 0.003; 2 =
0.110, respectively) (Fig. 3C). Increased third
trimester EPDS and HAM-D scores were also
associated with increased neonatal methylation
levels at CpG3 ( = 0.244; t = 2.105, p = 0.039, 2
= 0.054 and = 0.284, t = 2.314, p = 0.023, 2 =
0.065, respectively) (D).
Figure 4. (A) Cortisol stress change score at
three months and neonatal methylation status
at CpG3 site. (B) Direction of cortisol change
with stress at three months and CpG3
neonatal methylation levels. Increased
cortisol change with the stress/challenge was
associated with significantly greater NR3C1
methylation at CpG3 in newborns ( = 0.390,
t = 2.466, p = 0.018, 2 = 0.110), controlling
for third trimester maternal mood (EPDS
scores) and parental stress report at three
months (PSI) (A). Infants who responded with
increased cortisol levels had significantly
higher NR3C1 CpG3 meth- ylation status
compared with infants whose cortisol levels
declined in response to the three-month
stress [F(1,50) = 7.115; p = 0.010] (B).
Conclusiones
SRI: No asociado con metilacin
Estado de animo en el tercer semestre
CpG2 en segundo y tercer trimestre: Sensible
CpG3: Relacin metilacin y sntomas

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