Creationists often imagine the human body as the handiwork of a supreme intelligence, carefully engineered for optimal function. Yet the reality revealed by biology is far messier. Our anatomy and physiology are riddled with compromises, inefficiencies, and vulnerabilities that make far more sense as the outcomes of evolutionary processes than as the products of intelligent design. I give multiple examples of the results of these sub-optimal evolutionary compromises in my book, The Body of Evidence: How the Human Body Refutes Intelligent Design. One striking example lies in the complex relationship between mother and foetus during pregnancy, where cooperation and conflict are locked in an evolutionary arms race.
In a paper published in the Proceedings of the National Academy of Sciences (PNAS), Associate Professor Kshitiz of the Department of Biomedical Engineering, University of Connecticut, together with postdoctoral fellows Yasir Suhail and Wenqiang Du, Gunter Wagner of Yale, and Junaid Afzal of the University of California San Francisco (UCSF), have shown how the interface between mother and foetus in the placenta is the product of evolutionary arms races—not the result of intelligent design, as creationists like to imagine.
Firstly, there is the need for the developing foetus to obtain an adequate supply of nutrients, which requires its placental cells to penetrate into the lining of the mother’s uterus.
Secondly, there is the need for the mother to defend herself against invasion by what her body recognises as a ‘foreign’ organism, part of her evolved immune response. Finally, there is the overarching evolutionary imperative of successful reproduction, which entails the birth of healthy offspring.
What the team discovered is that the inevitable evolutionary compromise involves the foetus’s placental cells producing a protein that suppresses the mother’s immune response. This suppression works only because the mother’s cells have evolved to cooperate, allowing the foetal protein to function.
In other words, the mother’s cells have evolved a strategy for permitting the foetus to dampen her immune system—an immune system that itself evolved in the ancestors of placental mammals. This situation can hardly be credited to the act of a supreme intelligence.
Like all evolutionary compromises, this arrangement is predictably suboptimal and can sometimes fail, resulting in problems such as placenta accreta and preeclampsia. In The Body of Evidence: How the Human Body Refutes Intelligent Design (p. 103), I explain how preeclampsia in humans is the consequence of this evolutionary compromise. Because of the increased nutritional demands of the foetus to grow a large brain, it induces an increase in the mother’s blood pressure—a mechanism that can sometimes overshoot, causing dangerously high blood pressure, occasionally with fatal consequences for both mother and baby.
When the Compromise Fails^ Pregnancy Complications.This research is the subject of an article in the University of Connecticut’s online news outlet, UConn Today, by Courtney Chandler.The delicate balance between foetal demands and maternal defences is an evolutionary compromise that usually works—but not always. When it breaks down, the results can be serious:These complications remind us that pregnancy is not the product of perfect design but of an ongoing evolutionary arms race.
- Preeclampsia - Foetal signals raise maternal blood pressure to improve nutrient delivery, but sometimes overshoot, causing dangerously high blood pressure, organ damage, and risks to both mother and child.
- Placenta Accreta - Placental cells invade too deeply into the uterine wall, leading to severe bleeding at birth and often requiring surgery.
- Miscarriage - Failures in immune tolerance at the maternal–foetal interface may cause the mother’s immune system to reject the pregnancy.
- Preterm Birth - Inflammatory responses at the interface can trigger early labour, reducing survival and long-term health prospects for the infant.
Cooperation and Competition: How Fetal and Maternal Cells Evolved to Work Together
Study published in PNAS reexamines the dogma of genetic conflict in the maternal-fetal interface
The maternal-fetal interface is the meeting point for maternal and fetal cells during pregnancy. It’s been long understood as an area of conflict, where the placenta–a fetal organ– invades the mother to access nutrients.
This is an unusual situation because, in a normal case, foreign cells should be rejected by the immune system. During pregnancy, they are tolerated. However, mother’s cells also limit this invasion to an optimal state. The fight has continued for millions of years in evolution.
In the latest issue of the Proceedings of National Academy of Sciences (PNAS), Kshitiz, associate professor of biomedical engineering at the UConn School of Dental Medicine, demonstrates that pregnancy is not solely a conflict between mother and baby, rather, a delicate balance of cooperation and competition that has evolved overtime to ensure a successful pregnancy.
Postdoctoral fellows Yasir Suhail and Wenqiang Du, along with Gunter Wagner at Yale and Junaid Afzal at the University of California San Francisco (UCSF) also contributed to this research.
Wagner, former chair of evolutionary biology at Yale, and Kshitiz previously argued that there has to be cooperation between the mother and the fetus in order to sustain the pregnancy. Although the scientific discipline has mostly talked about genetic conflict, evidence of cooperation which modulates this conflict has been lacking.
The maternal fetal interface, for this is what the placenta-uterus interaction is called, is like an unresolved frontier between countries. There is so much difference between different species, which is not found for any other organ.
Associate Professor Kshitiz, senior author.
Department of Biomedical Engineering
University of Connecticut Health Farmington, CT. USA.
In anticipation of pregnancy, the endometrium undergoes a process called decidualization, the thickening of the tissue which women experience in each menstrual cycle. This process of deposition of matrix prevents excessive invasion by placental cells into the endometrium. Afzal and Du, demonstrated that placental cells influence the mother’s own cells to degrade their own matrix– a very surprising finding.
It is this active persuasion by the placental cells which made the mother’s endometrial cells to reduce her own defenses by secreting a protein, which was so surprising.
DR. Günter P. Wagner, co-author.
Department of Ecology and Evolution
Yale University, New Haven, CT, USA.
Suhail modeled the molecular interactions between placental and endometrial cells as an electric flow problem, identifying the key circuit underlying this manipulation.
It is rare, and heartening to see such close integrated collaboration between computation, and experimentation. My model was created by experimental data, and the discovery was validated by experiments.
Yasir Suhail, co-lead author
Department of Biomedical Engineering
University of Connecticut Health Farmington, CT. USA.
In game theory, the mix of competition and cooperation is known as co-opetition. The maternal-fetal interface, the researchers found, is home to a myriad of cell interactions that embody the true meaning of co-opetition.
Kshitiz credits a conversation with an economics professor from the United Kingdom, Dr. Anshuman Chutani, who told him about the extensive literature in econometrics on co-opetition.
It is a term which we gladly borrowed. It is not merely cooperation by the endometrium, but an induced cooperation between competitors.
Associate Professor Kshitiz.
In the maternal-fetal interface, the fetal cells work to actively persuade maternal cells to stop building protective tissue so that fetal cells can effectively invade the placenta and retrieve nutrients. Crucially, this interaction does not happen alone—it depends on the mother’s cells own readiness to respond to signals coming from the placenta. This proves that placental invasion is more of a combination of competition and cooperation between maternal and fetal tissues, not simply an area of conflict as previously believed.
This discovery does not only shed light on pregnancy complications that involve problems with placental invasion, such as placenta accreta and preeclampsia, but may also have broader implications on cancer metastasis and understanding how certain cancers invade the body.
Publication:This study, jointly conducted by scientists at UConn Health, Yale, and UCSF, can shift the way we think about conflict between the generations, right during when the fetus is still in mother’s womb.
Associate Professor Kshitiz.
SignificanceThis study highlights once again that what we see in human biology is not evidence of foresight or intelligent planning, but of evolutionary trial and error. The placenta is not a perfect, purpose-built system but a negotiated truce between mother and foetus, each shaped by competing evolutionary pressures. Its very fragility and tendency to fail under stress reveal the limits of natural processes, not the handiwork of a supreme engineer.
Intimate interactions between fetal and maternal cells are a hallmark of reproduction in placental mammals. In this contribution, we demonstrate that a cell from the (fetal) placenta affects the gene expression of the maternal placental bed in a way that enhances the invasion of the placenta into maternal tissues. This interaction, however, also depends on specific modifications of the maternal response to the placental signals. We interpret this to suggest that maternal evolutionary adaptations contributed to the fetal–maternal interaction enhancing implantation success, rather than being one solely driven by fetal adaptations. Placental invasion could therefore be described as a combination of competition and cooperation between the maternal and fetal tissues.
Abstract
Coopetition is a term from game theory that describes a mix of cooperative and competitive behavior. The maternal–fetal interface (MFI) among eutherian mammals presents close interaction of two distinct individuals. These interactions have resulted in a remarkable diversity in MFI structure, often interpreted as the outcome of maternal–fetal conflict. Nevertheless, the fetus and the mother share evolutionary interests since 50% of fetal genes are maternal. In hemochorial species, characterized by invasive placentation, endometrial stromal fibroblasts (ESFs) undergo decidualization to regulate embryo implantation. In great apes, hemochorial placentation is driven by highly invasive extravillous trophoblast cells (EVT). Here, using EVTs differentiated from trophoblast stem cells, term placenta, as well as HTR8/SVneo, we demonstrate that EVTs orchestrate a transformation of the maternal stroma, reducing its resistance to invasion acquired during decidualization. Through paracrine signals, in particular IL-11, trophoblasts transform decidual ESFs from a matrix-producing to a matrix-degrading state. Notably, noninvasive cytotrophoblast cells, do not transform decidual ESFs. We further provide evidence that maternal coadaptation is critical to EVT-induced decidual transformation. Decidual ESFs upregulate expression of Suppressor of Cytokine Signaling 3 in response to EVTs, rewiring downstream IL-11 signaling from JAK/STAT to AP-1 specific transcription. We conclude that the evolution of highly invasive placentation is the outcome of both the evolution of invasive EVTs, as well as the evolution of maternal traits, i.e., the switch from JAK/STAT to AP-1 signaling. We interpret this as evidence for co-opetition (cooperation among competitors).
J. Afzal, Y. Suhail, W. Du, Y. Liu, R. Ramasamy, Z. Liu, R. Goyal, A. Novin, S. Suhail, J. Maziarz, K. Wali, P. Robson, G.P. Wagner, & Kshitiz
Evidence for coopetition at the maternal–fetal interface shaping placental invasion Proc. Natl. Acad. Sci. U.S.A. 122(36) e2323038122, https://doi.org/10.1073/pnas.2323038122 (2025).
© 2025 The National Academy of Science of the USA.
Reprinted under the terms of s60 of the Copyright, Designs and Patents Act 1988.
Creationists may wish to imagine pregnancy as a flawless miracle of design, but the scientific evidence points in the opposite direction. The placenta is an extraordinary adaptation, yet one riddled with compromises, risks, and failure points. It exemplifies how evolution produces “good enough” solutions that enable survival and reproduction—solutions that would be hard to reconcile with the idea of a perfect creator. In addition, the fact that these compromises resulted in different solutions in different species, speaks loudly of evolution in an organ which is unique to the recently-evolved placental mammals, and against intelligent design.
As with so many other aspects of our anatomy and physiology, the truth revealed by science is richer and far more fascinating than creationist fables. By recognising these evolutionary compromises, we gain not only a deeper understanding of human biology, but also a clearer view of why medicine must contend with conditions such as preeclampsia, placenta accreta, miscarriage, and preterm birth. These are not flaws in a divine plan, but the predictable outcomes of our evolutionary history—something I explore in greater depth in my book, The Body of Evidence: How the Human Body Refutes Intelligent Design (see below).
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