Please cite this article in press as: Robillard, P.-Y., et al., An essay of reflection: Why does preeclampsia exist in humans, and why are there such huge geographical differences in epidemiology? J. Reprod. Immunol. (2015), http://dx.doi.org/10.1016/j.jri.2015.07.001 ARTICLE IN PRESS G Model JRI-2344; No. of Pages 4 Journal of Reproductive Immunology xxx (2015) xxx–xxx Contents lists available at ScienceDirect Journal of Reproductive Immunology jo u r n al homep age: www.elsevier.com/locate/jreprimm An essay of reflection: Why does preeclampsia exist in humans, and why are there such huge geographical differences in epidemiology? Pierre-Yves Robillard a,∗ , Gustaaf Dekker b , Silvia Iacobelli a , Gérard Chaouat c a Neonatology, Centre Hospitalier Universitaire Réunion, Centre d’Etudes Périnatales Océan Indien, BP 350, 97448 Saint-Pierre Cedex, Réunion, France b Head Women’s and Children’s Division, Lyell McEwin Hospital. University of Adelaide, Haydown Road, Elizabeth Vale 5112, South Australia, Australia c INSERM U 976, Pavillon Bazin, Hôpital Saint-Louis, 75010 Paris, France a r t i c l e i n f o Article history: Received 2 April 2015 Received in revised form 15 June 2015 Accepted 3 July 2015 Keywords: Preeclampsia Epidemiology Immunology Neonates a b s t r a c t This workshop had four main objectives: (A) Trying to look at the preeclampsia (PE) problem “from the Space Shuttle”: why preeclampsia has emerged in humans (a specific human reproductive feature among 4300 mammal species)? (B) Epidemiology: there are major geographical differences concerning early onset PE and late onset PE throughout the world. (C) Vascular: The very promising use of pravastatin in the treatment of the vascular maternal syndrome (based on the metabolism of carbon monoxide (CO), the role of inositol phosphate glycans P-type (IPG-P), a major role in comprehending the insulin resistance phenotype in preeclampsia. (D) Immunology: the specialty of these workshops since their start in 1998; our understanding of the role of the immune system and the regulation of the deep implantation of the human trophoblast (and the obligatory compromises between the fetal/placental unit and the mother) have reached a kind of “maturity,” following the pivotal studies exploring the biology of repetitive sperm exposure in the female genital tract. The meeting of people who never meet each other in the course of their normal professional lives (obstetricians, evolutionists, geneticists, immunologists, fundamen- talist vascular biologists, epidemiologists, anthropologists, neonatologists, etc.) permitted some fruitful reflections to be made again this year. © 2015 Elsevier Ireland Ltd. All rights reserved. 1. Introduction This paper tries to recall the four main objectives of the 2014 workshop on Reunion Island: (A) Reflection on preeclampsia (PE) in the light ofevolution: why has preeclampsia emerged in humans (and not in other mammals)? (B) Epidemiology: emerging at the end of the 1990s and reaching a large consensus around 2005–2006, there are two different kinds of PE, roughly before and after the 34th week of gesta- tion, i.e., early onset and late onset PE. Our reflections will show that there are indeed major geographical differences concern- ing early onset PE and late onset PE in the world. (C) The obligatory discussion on the vascular aspects of PE leading to global endothelial cell disease in mothers. (D) The state of the art concerning reproductive immunology and PE. ∗ Corresponding author. E-mail address: robillard.reunion@wanadoo.fr (P.-Y. Robillard). 1.1. Preeclampsia and evolution Since humans have been able to trace their cultures with the invention of writing 5000 years ago, throughout the world, in Asia (Middle and Far East), Europe (Greece), and Africa (Egypt), there have been reports of terrifying events at the time of giving birth of convulsions (often resulting in the death of the young parturi- ent, and therefore the newborns), i.e., eclampsia (Lindheimer et al., 1999). The invention of writing is by definition the beginning of written history, and if human history is seen on a 24-hour time scale, written history started at 22:34 of the accepted (minimum) existence of Homo Sapiens of 100,000 years (agriculture occurred at 21:36, Jesus Christ–the present international calendar – at 23:31). Humans have lived for 22:34 min in “pre”-history. Of course, there are no formal medical reports of epileptic seizures, in the “medical literature,” since physicians did not exist as such. But convulsions are such a spectacular event that you do not need to be a physician to make the diagnosis, and these convulsions have been interpreted in all cultures as a sign of being possessed by bad spirits or, later, by evil. To illustrate the terror that convulsions at birth provoked in our ancestors, we have as an example a semantic relic in mod- ern French slang: one of the words for “to die” is: “clamser” or http://dx.doi.org/10.1016/j.jri.2015.07.001 0165-0378/© 2015 Elsevier Ireland Ltd. All rights reserved.