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“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 QuickTime™ and a Photo - JPEG decompressor are needed to see this picture. 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