The placenta carries DNA from both mother and father, just like the fetus it supports. But when researchers look at which genes are actually switched on in placental tissue, the father’s contribution looms surprisingly large. A landmark study using RNA sequencing identified a core group of 15 ancient imprinted genes active in the placenta, and ten of those were paternally expressed; an additional 78 candidate imprinted genes also showed a paternal bias in the placenta but not in the fetus itself.1PubMed Central. Paternally expressed genes predominate in the placenta So the placenta is not “made by” the father’s genes in the sense that it contains only his DNA, but his genes do exert an outsized influence on how the organ builds itself and behaves.
Both Parents Contribute DNA, but Not Equally in Activity
Every cell in the placenta starts with a complete set of chromosomes, half from the egg and half from the sperm. In that sense, the placenta is a fifty-fifty genetic collaboration. What makes the organ unusual is a phenomenon called genomic imprinting, where certain genes are effectively silenced depending on which parent passed them along. In most of the body, both copies of a gene can be active. In imprinted regions, only the maternal or paternal copy gets to “speak.” The placenta and the brain are the two tissues where the highest number of imprinted genes have been found.2PubMed Central. Placental imprinting: Emerging mechanisms and functions
The tilt toward paternal expression in the placenta is not subtle. Of the core ancient imprinted genes identified in one large analysis, two-thirds were paternally expressed. The 78 additional candidates showing paternal bias were especially interesting because their imprinting appeared to be placenta-specific: those same genes did not show parent-of-origin bias in the fetal body.1PubMed Central. Paternally expressed genes predominate in the placenta In other words, the father’s genetic influence is amplified in the placenta compared to almost anywhere else in the developing pregnancy.
The Evolutionary Logic Behind Paternal Dominance
Why would evolution favor a system where the father’s genes push harder in the placenta? The most widely accepted explanation is the genetic conflict hypothesis, sometimes called the kinship theory. The idea centers on a tension between the interests of the two parental genomes. A mother’s body will, on average, carry multiple pregnancies over her lifetime, possibly with different fathers. Her genes “want” to distribute resources across all of her offspring. But the father’s genes, which may not be present in the mother’s future pregnancies, benefit from extracting as much as possible during this one.3PubMed. The conflict theory of genomic imprinting: how much can be explained?
Under this framework, paternally expressed genes in the placenta tend to promote fetal growth and nutrient acquisition, while maternally expressed genes tend to restrain those same processes. The placenta is the battlefield where these competing interests play out, and it explains why so many of the growth-promoting genes active there are the copies inherited from the father.
What Paternal Genes Actually Do in the Placenta
The most studied paternally expressed gene in placental tissue is IGF2, which encodes a growth factor critical for building the nutrient-exchange machinery. Mouse experiments have shown exactly how powerful this gene is. When the placenta-specific version of IGF2 was knocked out, placental weight dropped to about two-thirds of normal, and the theoretical capacity for nutrient exchange through the placenta plummeted to roughly 40% of what it would be in a normal pregnancy. The surface area of the exchange barrier shrank and the barrier itself thickened, making it harder for nutrients to cross from mother to fetus.4PubMed Central. Placental-specific insulin-like growth factor 2 (Igf2) regulates the diffusional exchange characteristics of the mouse placenta
More recent work has shown that IGF2 does not just set the placenta’s initial size. It also drives the expansion of the tiny blood vessels inside the placenta that are responsible for actual nutrient transfer in later pregnancy. Deleting the paternal IGF2 copy from the fetal blood-vessel lining caused moderate but significant growth restriction in both the placenta and the fetus from mid-gestation onward. Full expansion of the placental exchange zone in late pregnancy required IGF2 coming from both the fetus itself and the blood-vessel lining, though not from blood cells.5PubMed Central. The imprinted Igf2-Igf2r axis is critical for matching placental microvasculature expansion to fetal growth The takeaway is that the father’s copy of this single gene shapes both the architecture and the functional capacity of the placenta at multiple stages of development.
A parallel story exists in the labyrinth zone of the mouse placenta, where genes enriched in the exchange layers include a significant number of autosomal imprinted genes and maternally biased X-linked genes.6Genome Biology and Evolution. Evolution of Gene Expression Across Functional Regions of the Mouse Placenta The interplay between paternally and maternally expressed genes in these layers is not one-sided; it is a tightly regulated negotiation, with both sides contributing to the final structure.
What Happens When Only the Father’s Genome Is Present
Some of the clearest evidence for the paternal genome’s role in the placenta comes from pregnancies that go wrong in specific, instructive ways. A complete hydatidiform mole is a pregnancy in which the embryo receives two sets of paternal chromosomes and no functional maternal set. The result is a mass of abnormal placental tissue that grows aggressively but produces no viable fetus. Partial moles, which carry two paternal sets and one maternal set, also show abnormal placental overgrowth. In both cases, the overrepresentation of paternal DNA leads to a global shift in imprinted gene expression in the placental tissue.7PubMed. Hydatidiform Moles: Genetic Basis and Precision Diagnosis
The opposite experiment is also revealing. Parthenogenetic embryos, created from egg cells that begin developing without sperm and therefore have only maternal DNA, can survive to mid-gestation in mice. But they invariably die, and the cause is telling: their trophoblast and yolk sac, the tissues that form the placenta and its support structures, are dramatically underdeveloped.8PubMed. Abnormal development of embryonic and extraembryonic cell lineages in parthenogenetic mouse embryos These two natural experiments paint a consistent picture. Too much paternal genome yields runaway placental growth with no viable embryo. Too little paternal genome yields a stunted placenta that cannot sustain even a normal embryo. The father’s genetic contribution is essential for building a functional placenta, but it needs the mother’s genes to keep it in check.
In rare cases, women experience recurrent complete moles, and researchers have traced some of these to mutations in the mother’s own genes that disrupt normal egg formation, producing oocytes whose maternal chromosomes are lost after fertilization. Roughly 5% of oocytes from mice lacking one such gene led to androgenetic (fully paternal) embryos after fertilization.9American Journal of Human Genetics. MEI1, TOP6BL/C11orf80, and REC114 Mutations Cause Human Recurrent Androgenetic Complete Hydatidiform Moles These findings reinforce that the balance between paternal and maternal genomes is not a quirk of gene regulation; it is a structural requirement for building a placenta that works.
Preeclampsia and Disrupted Imprinting
When the carefully balanced imprinting system in the placenta goes haywire, the consequences can extend to the mother’s health. Preeclampsia, a pregnancy complication involving dangerously high blood pressure and organ damage, has been linked to altered expression of imprinted genes in placental tissue. Studies have found that imprinted genes are more frequently dysregulated in preeclamptic placentas than you would expect from a random selection of genes. And the direction of the disruption is consistent with the conflict theory: the patterns of altered expression tend to reduce nutrient allocation to the fetus, as if the balance has tipped too far in the maternal-restraint direction.10PubMed Central. Associations between imprinted gene expression in the placenta, human fetal growth and preeclampsia
Specific genes have been identified in this process. The gene DLX5, which is normally imprinted, shows disturbed imprinting in preeclamptic placentas, leading to abnormally high expression that affects how placental cells multiply.11PubMed Central. Disturbed Placental Imprinting in Preeclampsia Leads to Altered Expression of DLX5, a Human-Specific Early Trophoblast Marker Other research has found increased levels of several imprinted genes in early-onset preeclamptic placentas, including PEG3, IGF2, and DLK1, and intriguingly, the fathers in these pregnancies showed methylation differences in their sperm.12PubMed. Methylation aberrations in partner spermatozoa and impaired expression of imprinted genes in the placentae of early-onset preeclampsia This finding adds a new dimension to the question of paternal influence: it suggests that the father’s contribution to placental function may begin before conception, through the epigenetic state of his sperm.
Paternal Age and Sperm Epigenetics
The idea that a father’s biology at the time of conception can shape the placenta has gained traction from research into paternal age. As men age, chemical modifications accumulate on their sperm DNA. A study examining these changes found that about 7% of the genes showing age-related methylation shifts in the placenta overlapped with genes previously found to be altered in the sperm of older men. Seven of those shared genes had also been flagged in research on autism susceptibility.13PubMed Central. Advanced Paternal Age Impacts Common Loci in the Sperm and Placenta DNA Methylomes The research is still early, but it raises the possibility that a father’s age and health at the time of conception could influence how the placenta develops and functions, separate from the DNA sequence he passes along.
IVF and the Fragility of Imprinting
Assisted reproductive technologies add another layer to this story. The processes involved in IVF and related techniques expose eggs, sperm, and early embryos to laboratory conditions during a critical window when imprinting marks are being established and maintained. Research comparing placentas from IVF pregnancies to those from naturally conceived pregnancies has found changes in methylation at imprinted regions, along with reduced expression of a gene involved in stabilizing those marks.14Communications Medicine. Genome-wide DNA methylation and gene expression in human placentas derived from assisted reproductive technology
More detailed analysis has shown that two key imprinted regions, H19/IGF2 and KCNQ1OT1, had significantly lower methylation in IVF placentas. That reduced methylation was accompanied by changes in the chemical tags on the proteins that DNA wraps around, shifting toward a more “open” configuration that allows genes to be read more freely.15PubMed Central. The hypomethylation of imprinted genes in IVF/ICSI placenta samples is associated with concomitant changes in histone modifications H19/IGF2 is the same region that controls the paternally expressed growth factor discussed earlier, so perturbation of its imprinting in the placenta is not a trivial finding. Most IVF pregnancies result in healthy babies, but these molecular differences suggest the system has less margin for error than it does in naturally conceived pregnancies, and they underscore how sensitive the father’s genetic influence in the placenta is to environmental disruption.
The X Chromosome Adds Another Twist
Imprinting in the placenta is not limited to growth genes on non-sex chromosomes. The X chromosome tells its own story. In female embryos, one X chromosome is randomly silenced in most tissues to avoid a double dose of X-linked genes. But in the placenta, the process is not random. In mice, rats, cows, and marsupials, the paternal X chromosome is preferentially silenced in placental tissue. Human placentas show a similar but messier pattern: researchers found that the paternal X was consistently the one being silenced, though the pattern varied from one region of the placenta to another, and some areas showed both X chromosomes being expressed or opposite silencing at different extraction sites.16bioRxiv. Patchy, incomplete, and heterogeneous X-inactivation in the human placenta
The preferential silencing of the paternal X in the placenta has a conceptual link to the conflict framework. Silencing genes on the paternal X would reduce the dosage of paternally inherited X-linked genes, potentially serving as a maternal counterbalance to the paternal bias seen in autosomal imprinted genes. The patchiness of the pattern in humans, compared to the cleaner imprinting seen in mice, hints that the system is still evolving and may be less tightly regulated in our species.
How the Placenta Avoids Immune Rejection
The father’s genetic contribution to the placenta creates an immunological puzzle. The placenta, by definition, carries proteins encoded by paternal DNA. These proteins are foreign to the mother’s immune system and should, in theory, trigger an attack. Yet the fetus is not rejected. The placenta itself is a key part of the solution. Fetal cells in the placenta carry immune markers inherited from the father, but through a combination of selective gene silencing and active immune suppression, these markers do not provoke the kind of rejection you would see in, say, an organ transplant.17PubMed Central. Role of maternal-fetal immune tolerance in the establishment and maintenance of pregnancy
The evolution of placental mammals required solving this problem. The fetus expresses paternal antigens that are fully capable of triggering immune rejection, and the maternal immune system has had to develop specialized tolerance mechanisms to coexist with them.18Cell. Maternal-Fetal Immune Tolerance, Block by Block Part of the solution involves specialized immune cells in the uterus, and part involves the placenta itself limiting which paternal proteins it displays on its outer surface. The outer layer of the human placenta, the syncytiotrophoblast, is a continuous multinucleated sheet formed from the fusion of underlying cells, and it expresses very few of the standard immune-recognition molecules that would flag it as foreign.
Viral Genes That Built the Placenta
The placenta’s outer layer has an unexpected origin story that complicates any simple assignment of credit to “father’s genes” or “mother’s genes.” The syncytiotrophoblast, the fused cell layer responsible for nutrient transport and immune shielding, relies on proteins called syncytins to form. These proteins are not standard mammalian genes. They were originally envelope proteins from ancient retroviruses that infected mammalian ancestors millions of years ago. Over evolutionary time, the viral genes became permanently integrated into the host genome and were repurposed to drive the cell-cell fusion that creates the syncytiotrophoblast.19PubMed. Evolutionary co-option of endogenous retroviruses: syncytins as regulators of placental development and disease These viral-origin genes sit in the genomes of both parents and are inherited like any other gene, so they do not favor one parent over the other. But they are a reminder that the placenta’s genetic toolkit is drawn from sources far stranger than a simple maternal-paternal split would suggest.
Fetal Cells Carrying Paternal DNA Persist in the Mother
The father’s genetic reach through the placenta does not end at delivery. During pregnancy, small numbers of fetal cells cross the placenta into the mother’s bloodstream and take up residence in her tissues, a phenomenon called fetal microchimerism. These cells carry paternal DNA and have been detected in maternal blood, skin, liver, and other organs years or even decades after pregnancy.20PubMed Central. Fetal microchimerism and implications for maternal health
The effects of these persistent fetal cells on the mother’s long-term health are still being worked out, and the picture is mixed. Some research suggests fetal cells may contribute to wound healing and tissue repair. Other work has linked them to increased risk of certain autoimmune conditions. The evolutionary framework for understanding this mirrors the conflict theory of imprinting: fetal cells carrying paternal genes may sometimes act in the mother’s interest by repairing damaged tissue, while in other contexts they may manipulate maternal physiology to enhance resource transfer to current or future offspring, such as by influencing milk production.21PubMed Central. Fetal microchimerism and maternal health: a review and evolutionary analysis of cooperation and conflict beyond the womb Either way, fetal microchimerism means the father’s genetic material, originally introduced through the placenta, can have biological effects on the mother long after the pregnancy ends.