Transcript Growth hormone - Life Sciences Outreach at Harvard University

“A gentle immunological balance thus
has to be maintained in the decidua,
where immunological activity
operates to eliminate a pathogen
without damaging the fetus”
Markel et al. (2002)
Journal of Clinical Investigation 110: 943
“The border zone … is not a sharp line, for it
is in truth the fighting line where the conflict
between the maternal cells and the invading
trophoderm takes place, and it is strewn with
such of the dead on both sides as have not
already been carried off the field or otherwise
disposed of.”
Johnstone (May 1914)
Journal of Obstetrics and Gynaecology of the British Empire 25: 231
Maternal provisioning of a
fetus is associated with an
opportunity cost
The opportunity cost
translates into lower
expected fitness through
other offspring
If extra resources are
transferred to an embryo
the embryo’s expected
fitness increases
the mother’s expected
fitness from other
offspring decreases
benefit
maternal investment in fetus
cost to siblings
benefit to fetus
cost
benefit
X
X minimizes cost to siblings
cost to siblings
benefit to fetus
cost
benefit
X
Z
Z maximizes benefit to fetus
cost to siblings
benefit to fetus
cost
benefit
X
Y
Z
Y maximizes (benefit — cost)
cost to siblings
benefit to fetus
cost
mother
maternal
(non-inherited)
maternal
(inherited)
paternal
(inherited)
fetus
Relative shares
Benefit
(to fetus)
Cost
(to sibs)
maternal
(non-inherited)
0
1/2
maternal
(inherited)
1
1/2
paternal
(inherited)
1
p/2
gene
p = probability of shared paternity
A non-inherited maternal
gene gains no benefit
from the survival and
reproduction of a fetus
worse than that!
Non-inherited maternal
genes will benefit from
the early demise of the
fetus
How is pregnancy possible?
rarity of genetic self-recognition
“the parliament of the genes”
(mutual policing)
Paternally-derived genes
in fetuses favor greater
demands on mothers than
maternally-derived genes
PRONUCLEAR SUBSTITUTIONS
egg nucleus
sperm nucleus
fetus
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yolk sac
trophoblast
mum
+
dad
mum
+
mum
dad
+
dad
46,XX paternal origin
massively proliferating placental tissues
1,000-fold increased risk of
choriocarcinoma
46,XX maternal origin
ovarian teratomas; benign
produce most tissues (but not placenta)
mother
maternal
(non-inherited)
maternal
(inherited)
paternal
(inherited)
fetus
incomplete information
mother
fetus
Benefit
(to fetus)
Cost
(to sibs)
1/2
1/2
1
(1+p)/4
p = probability of shared paternity
spiral artery
umbilical cord
uterine vein
Conflict can exist over
whether or not to miscarry
the nutrient quality of
maternal blood
the volume of blood reaching
the placenta
ovulation
(day 0)
hCG (day 7)
CL regresses
(days 8-10)
onset of menstruation
(day 14)
women attempting to conceive
number of cycles
707
chemical pregnancies
198
clinical pregnancies
155
term pregnancies
136
data from Wilcox et al. (1988)
anterior pituitary
luteinizing
hormone
corpus luteum
progesterone
uterus
anterior pituitary
luteinizing
hormone
chorionic
gonadotropin
placenta
corpus luteum
progesterone
uterus
anterior pituitary
luteinizing
hormone
chorionic
gonadotropin
placenta
progesterone
corpus luteum
progesterone
uterus
CONCENTRATIONS IN MATERNAL SERUM
non-pregnant
pregnant
hLH/hCG
100 mIU/ml
50,000 mIU/ml
hGH/hPL
5 ng/ml
10,000 ng/ml
10 ng/ml
200 ng/ml
0.4 ng/ml
20 ng/ml
progesterone
estradiol
Placental hormones
Why shout?
Placental hormones originate
as fetal attempts to
manipulate maternal
physiology for fetal benefit
Placental hormones may
evolve to become little more
than endocrine SPAM
maternal carbohydrate metabolism
• fasting blood glucose falls in first
trimester
• maternal sensitivity to insulin
decreases as pregnancy progresses
• maternal insulin production increases
in parallel with reduced sensitivity
maternal blood pressure in
pregnancy
• blood pressure reduced during most
pregnancies; rises toward term
• ≈ 10% women develop hypertension
= pregnancy-induced hypertension (PIH)
• preeclampsia (PIH + proteinuria)
affects ≈ 3% pregnancies
Uteroplacental
resistance
Non-placental
resistance
Placental factors
decrease
increase
Maternal factors
increase
decrease
Maternal-fetal relations
lack important feedback
controls because signals
are not evolutionarily
credible
non-pregnant mothers of sons
time since birth
of last son
XY cells
in blood
6 months
10 months
12 months
2 yrs
3 yrs
6 yrs
7 yrs
27 yrs
no
no
yes
yes
yes
yes
yes
yes
data from Bianchi et al. (1996)
PRONUCLEAR SUBSTITUTIONS
data of E. B. Keverne
data of E. B. Keverne
Androgenetic/normal
chimeras have large bodies
with relatively small brains
Gynogenetic/normal chimeras
have small bodies with
relatively large brains
photos from E. B. Keverne
Contribution to brains of
chimeric mice
“two mums”
“two dads”
hypothalamus
neocortex
—
+++
+++
—
Keverne et al. (1996)
Developmental Brain Research 92: 91
Genomic imprinting concerns
differences between genomes
of maternal and paternal
origin, not differences
between males and females
PREGNANCY-INDUCED HYPERTENSION
Robillard et al. (1994) Lancet 344: 973
multigravidae
incidence of PIH
.4
.3
.2
.1
primigravidae
0—4
5—8
9—12
duration of sexual cohabitation (months)
>12