Markel et al. (2002) Journal of Clinical Investigation 110: 943

1. “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

2. “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

3. Maternal provisioning of a fetus is associated with an opportunity cost The opportunity cost translates into lower expected fitness through other offspring

4. If extra resources are transferred to an embryo the embryo’s expected fitness increases the mother’s expected fitness from other offspring decreases

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

6. cost benefit to fetus benefit cost to siblings X X minimizes cost to siblings

7. cost benefit to fetus benefit cost to siblings X Z Z maximizes benefit to fetus

8. benefit to fetus benefit cost cost to siblings X Y Z Y maximizes (benefit — cost)

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

10. maternal (non-inherited) 0 1/2 maternal (inherited) 1 1/2 paternal (inherited) 1 p/2 Relative shares Benefit (to fetus) Cost (to sibs) gene p = probability of shared paternity

11. A non-inherited maternal gene gains no benefit from the survival and reproduction of a fetus

12. worse than that!

13. Non-inherited maternal genes will benefit from the early demise of the fetus

14. How is pregnancy possible? rarity of genetic self-recognition “the parliament of the genes”(mutual policing)

15. Paternally-derived genes in fetuses favor greater demands on mothers than maternally-derived genes

16. egg nucleus sperm nucleus

17. fetus yolk sac trophoblast mum + dad mum + mum dad + dad

18. 46,XX paternal origin massively proliferating placental tissues 1,000-fold increased risk of choriocarcinoma

19. 46,XX maternal origin ovarian teratomas; benign produce most tissues (but not placenta)

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

21. mother 1/2 1/2 fetus 1 (1+p)/4 incomplete information Benefit (to fetus) Cost (to sibs) p = probability of shared paternity

23. spiral artery umbilical cord uterine vein

24. Conflict can exist over whether or not to miscarry the nutrient quality of maternal blood the volume of blood reaching the placenta

25. ovulation (day 0) hCG (day 7) CL regresses (days 8-10) onset of menstruation (day 14)

26. number of cycles chemical pregnancies clinical pregnancies term pregnancies 707 198 155 136 women attempting to conceive data from Wilcox et al. (1988)

27. luteinizing hormone progesterone anterior pituitary corpus luteum uterus

28. progesterone anterior pituitary luteinizing hormone chorionicgonadotropin corpus luteum placenta uterus

29. anterior pituitary luteinizing hormone chorionicgonadotropin corpus luteum progesterone placenta progesterone uterus

31. hLH/hCG 100 mIU/ml 50,000 mIU/ml hGH/hPL 5 ng/ml 10,000 ng/ml progesterone 10 ng/ml 200 ng/ml estradiol 0.4 ng/ml 20 ng/ml CONCENTRATIONS IN MATERNAL SERUM non-pregnant pregnant

32. Placental hormonesWhy shout?

33. Placental hormones originate as fetal attempts to manipulate maternal physiology for fetal benefit

34. Placental hormones may evolve to become little more than endocrine SPAM

35. 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

37. 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

38. Uteroplacentalresistance Non-placentalresistance Placental factors Maternal factors decrease increase increase decrease

40. Maternal-fetal relations lack important feedback controls because signals are not evolutionarily credible

41. time since birthof last son XY cellsin blood non-pregnant mothers of sons 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)

44. data of E. B. Keverne

45. data of E. B. Keverne

46. Androgenetic/normal chimeras have large bodies with relatively small brains

47. Gynogenetic/normal chimeras have small bodies with relatively large brains

48. photos from E. B. Keverne

49. Contribution to brains of chimeric mice hypothalamus neocortex “two mums” — + + + “two dads” + + + — Keverne et al. (1996)Developmental Brain Research 92: 91

50. Genomic imprinting concerns differences between genomes of maternal and paternal origin, not differences between males and females