“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

maternal investment in fetus benefit benefit to fetus cost cost to siblings

X minimizes cost to siblings benefit benefit to fetus cost cost to siblings X

Z maximizes benefit to fetus benefit benefit to fetus cost cost to siblings XZ

Y maximizes (benefit — cost) benefit benefit to fetus cost cost to siblings XZY

maternal (non-inherited) maternal (inherited) paternal (inherited) mother fetus

Relative shares p = probability of shared paternity gene Benefit (to fetus) Cost (to sibs) maternal (non-inherited) 01/2 maternal (inherited) 11/2 paternal (inherited) 1p/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

egg nucleussperm nucleus

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; benign produce 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) mother1/2 fetus1(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 data from Wilcox et al. (1988)

anterior pituitary corpus luteum uterus luteinizing hormone progesterone

anterior pituitary corpus luteum uterus placenta luteinizing hormone progesterone chorionic gonadotropin

anterior pituitary corpus luteum uterus placenta luteinizing hormone progesterone chorionic gonadotropin 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 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

Placental factors Maternal factors Uteroplacental resistance decrease increase Non-placental resistance 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 data from Bianchi et al. (1996) 6 months 10 months 12 months 2 yrs 3 yrs 6 yrs 7 yrs 27 yrs no yes

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