“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

embryothe embryo’s expected

fitness increasesthe mother’s expected

fitness from other offspring decreases

maternal investment in fetus

benefit

ben

efi

t to

fetu

s cost cost to

sib

ling

s

X minimizes cost to siblings

benefit

ben

efi

t to

fetu

s cost cost to

sib

ling

s

X

Z maximizes benefit to fetus

benefit

ben

efi

t to

fetu

s cost cost to

sib

ling

s

X Z

Y maximizes (benefit — cost)

benefit

ben

efi

t to

fetu

s cost cost to

sib

ling

s

X ZY

maternal(non-inherited)

maternal(inherited)

paternal(inherited)

mother

fetus

Relative shares

p = probability of shared paternity

geneBenefit

(to fetus)Cost

(to sibs)

maternal(non-inherited) 0 1/2

maternal(inherited) 1 1/2

paternal(inherited)

1 p/2

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

QuickTime™ and aPhoto - JPEG decompressor

are needed to see this picture.

fetus

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; benignproduce most tissues (but not

placenta)

maternal(non-inherited)

maternal(inherited)

paternal(inherited)

mother

fetus

incomplete information

p = probability of shared paternity

Benefit(to fetus)

Cost(to sibs)

mother 1/2 1/2

fetus 1 (1+p)/4

umbilical cord

spiral artery

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)

onset of menstruation(day 14)

CL regresses(days 8-10)

women attempting to conceive

number of cycles

chemical pregnancies

clinical pregnancies

term pregnancies

707

198

155

136

data from Wilcox et al. (1988)

anterior pituitary

corpus luteum

uterus

luteinizinghormone

progesterone

anterior pituitary

corpus luteum

uterus

placenta

luteinizinghormone

progesterone

chorionicgonadotropin

anterior pituitary

corpus luteum

uterus

placenta

luteinizinghormone

progesterone

chorionicgonadotropin

progesterone

CONCENTRATIONS IN MATERNAL SERUM

non-pregnant pregnant

hLH/hCG

hGH/hPL

progesterone

estradiol

100 mIU/ml

5 ng/ml

10 ng/ml

0.4 ng/ml

50,000 mIU/ml

10,000 ng/ml

200 ng/ml

20 ng/ml

Placental hormonesWhy 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 CIRCULATION DURING PREGNANCYplacentamaternaltissues

RpRm

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

Placental factors

Maternal factors

Uteroplacentalresistance

decrease

increase

Non-placentalresistance

increase

decrease

MATERNAL CIRCULATION DURING PREGNANCYplacentamaternaltissues

RpRm

Maternal-fetal relations lack important

feedback controls because signals are not evolutionarily credible

non-pregnant mothers of sons

time since birthof last son

XY cellsin blood

data from Bianchi et al. (1996)

6 months10 months12 months

2 yrs3 yrs6 yrs7 yrs27 yrs

nonoyesyesyesyesyesyes

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

hypothalamusneocortex

“two dads” + + + —

“two mums” + + +—

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