When pregnant people don’t eat enough calories, their babies can stop growing properly in the womb—a serious condition called fetal growth restriction. Scientists wanted to understand exactly how this happens at the cellular level. Using pregnant mice on reduced diets, researchers discovered that calorie restriction damages the placenta (the organ that feeds the baby) by reducing special cells that normally invade the uterine wall and create blood vessels. This study shows that poor nutrition disrupts multiple biological processes needed for healthy placental development, offering clues about why some pregnancies face complications and potentially leading to better treatments.

The Quick Take

  • What they studied: How eating fewer calories during pregnancy affects the placenta’s ability to grow and develop properly in mice, specifically looking at the cells and genes involved in placental growth.
  • Who participated: Pregnant laboratory mice were divided into two groups: one eating a normal diet and one eating 50% fewer calories. Researchers examined their placentas at five different stages of pregnancy to track changes over time.
  • Key finding: Mice on reduced-calorie diets had smaller babies and placentas starting around mid-pregnancy. Their placentas had fewer of the special cells needed to invade the uterine wall and create blood vessels, along with reduced activity of genes controlling these processes.
  • What it means for you: This research suggests that severe calorie restriction during pregnancy may harm placental development through multiple biological pathways. While this is mouse research and doesn’t directly apply to humans, it provides important clues about why maternal nutrition matters for fetal health. Pregnant people should consult healthcare providers about appropriate nutrition—not restrict calories without medical guidance.

The Research Details

Researchers conducted a controlled experiment using pregnant mice to mimic what happens during severe calorie restriction in pregnancy. Starting at day 8.5 of pregnancy (early development), they divided mice into two groups: one receiving normal food and one receiving 50% fewer calories. They then examined the placentas at five different time points throughout pregnancy (days 10.5, 12.5, 14.5, 16.5, and 17.5) to see how the placenta changed over time.

To understand what was happening at the cellular and molecular level, the researchers used several advanced techniques. They extracted genetic material from placental tissue to measure which genes were active or inactive. They also used special staining techniques to visualize specific cells under a microscope—looking for trophoblast cells (the cells that invade the uterine wall) and endothelial cells (the cells that form blood vessels). This multi-layered approach allowed them to see both the big picture (smaller babies and placentas) and the microscopic details (which genes and cells were affected).

The researchers used standard statistical methods to compare the two groups and determine whether differences were meaningful or just due to chance. This controlled, step-by-step approach helps ensure the findings are reliable and reproducible.

This research design is important because it allows scientists to study pregnancy complications in a controlled setting where they can carefully measure cause and effect. In humans, it’s impossible to deliberately restrict pregnant people’s calories for research purposes, so animal models provide crucial insights. By examining multiple time points, the researchers could see exactly when problems started and how they progressed—information that would be impossible to gather in human studies. The combination of genetic analysis and cell visualization helps identify not just that something went wrong, but why and how it happened at the biological level.

This study has several strengths: it used a systematic approach with multiple time points, employed multiple measurement techniques (genetic analysis and microscopy), and examined specific genes and cells with clear biological relevance. However, there are important limitations to consider. The study was conducted in mice, and mouse biology doesn’t always translate directly to humans. The researchers didn’t specify the exact number of animals used, which makes it harder to assess statistical power. The study focused on severe calorie restriction (50% reduction), which is more extreme than typical human nutritional challenges. Additionally, this is a single study in mice, so findings need confirmation in other research before drawing firm conclusions about human pregnancy.

What the Results Show

Calorie-restricted pregnant mice had noticeably smaller babies and placentas compared to mice eating normally, with these differences becoming clear around the middle of pregnancy and persisting through the end. By day 17.5 (near the end of mouse pregnancy), the restricted group showed significantly reduced placental development.

When researchers examined the placentas under a microscope, they found that calorie restriction reduced the depth of the decidua (the uterine lining where the placenta attaches) and decreased how far the trophoblast cells invaded into this tissue. There were also fewer trophoblast cells overall in the placentas of calorie-restricted mice. These findings suggest that the placenta’s ability to establish a strong connection with the uterus was compromised.

At the genetic level, calorie restriction reduced the activity of eight different genes involved in trophoblast invasion and cell movement. These genes normally help placental cells burrow into the uterine wall and establish the connections needed for nutrient exchange. The reduction in gene activity correlated with the reduced number of trophoblast cells observed under the microscope, suggesting a direct link between genetic changes and cellular changes.

The study also found reduced blood vessel formation in the placentas of calorie-restricted mice. Three genes involved in creating new blood vessels (Vegfa, Vegfb, and Akt3) showed reduced activity, and markers of blood vessel cells were also decreased. This means the placenta had fewer blood vessels to deliver oxygen and nutrients to the developing fetus.

Beyond the main findings about trophoblast invasion and blood vessel formation, the research revealed that calorie restriction affected multiple interconnected biological systems. The reduction in placental blood vessels (angiogenesis) appeared to be a consequence of the same nutritional stress that impaired trophoblast invasion. This suggests that severe calorie restriction doesn’t just affect one aspect of placental development but rather disrupts several critical processes simultaneously. The timing of these changes—becoming apparent around mid-pregnancy and persisting through late pregnancy—indicates that the early stages of placental development are particularly vulnerable to nutritional stress.

This research aligns with existing knowledge that placental insufficiency (when the placenta can’t adequately nourish the fetus) is a major cause of fetal growth restriction. Previous studies in humans have shown that maternal malnutrition is associated with poor pregnancy outcomes, and this mouse model provides a biological explanation for how that happens. The specific genes identified in this study match those previously implicated in placental development, lending credibility to the findings. However, most prior research has focused on single genes or pathways, whereas this study examined multiple interconnected systems, providing a more complete picture of how malnutrition affects the placenta.

Several important limitations should be considered when interpreting these findings. First, this research was conducted in mice, and while mice are useful models for understanding basic biology, their pregnancy and placental development differ from humans in important ways. Second, the study used severe calorie restriction (50% reduction), which is more extreme than most human nutritional challenges and may not reflect real-world pregnancy complications. Third, the researchers did not specify the number of animals used in each group, making it difficult to assess whether the study had enough power to detect real differences. Fourth, this is a single study, and findings need to be confirmed by other research teams before drawing firm conclusions. Finally, while the study identified which genes and cells were affected, it didn’t fully explain the mechanisms by which calorie restriction causes these changes, leaving some questions about the biological pathway unanswered.

The Bottom Line

Based on this research, the key recommendation is that pregnant people should maintain adequate calorie and nutrient intake under guidance from their healthcare provider. This study provides biological evidence supporting why maternal nutrition matters for fetal development. However, this is animal research, and pregnant people should never restrict calories without explicit medical supervision—doing so could harm both mother and baby. If someone is concerned about weight management during pregnancy, they should discuss this with their obstetrician or midwife, who can provide personalized guidance. The confidence level for this recommendation is moderate, as it’s based on mouse research that needs human confirmation.

This research is most relevant to pregnant people, healthcare providers managing pregnancy complications, and researchers studying fetal growth restriction. It’s particularly important for people in resource-limited settings where calorie restriction may be involuntary due to food scarcity. Healthcare providers can use these findings to better understand the biological mechanisms behind fetal growth restriction and potentially develop new treatments. The general public should understand that this is basic science research in mice and shouldn’t be used to make decisions about pregnancy nutrition without consulting healthcare providers. People who are not pregnant don’t need to apply these findings to their own health.

If these findings apply to humans, the effects of calorie restriction on placental development would likely begin in the first trimester (when the placenta is forming) and become progressively worse throughout pregnancy if the restriction continues. Improvements in nutrition would probably take weeks to months to show effects on placental function, and some damage might be permanent if it occurs during critical developmental windows. However, this timeline is based on mouse research and may differ significantly in humans.

Want to Apply This Research?

  • For pregnant users, track daily calorie intake and macronutrient distribution (protein, carbohydrates, fats) to ensure adequate nutrition. Set a target range based on healthcare provider recommendations (typically 300 additional calories per day in the second and third trimesters) and log meals daily. Monitor weight gain patterns to ensure they fall within recommended ranges for pre-pregnancy BMI.
  • Users can set daily nutrition goals within the app, such as consuming adequate protein (71 grams daily for pregnant people), iron-rich foods, and prenatal vitamins as recommended by their healthcare provider. The app could send reminders for meals and snacks, suggest nutrient-dense foods, and flag days when calorie or nutrient intake falls below recommended levels, prompting users to discuss concerns with their healthcare provider.
  • Establish a baseline of current nutrition habits, then gradually improve intake to meet pregnancy nutrition guidelines. Track weekly trends rather than daily fluctuations, and share monthly summaries with healthcare providers during prenatal visits. Monitor for warning signs like unintended weight loss or persistent inability to meet calorie goals, which should trigger a conversation with a healthcare provider about potential barriers to adequate nutrition.

This research was conducted in mice and does not directly apply to human pregnancy. Pregnant people should never restrict calories without explicit medical guidance from their healthcare provider. If you are pregnant or planning to become pregnant, consult with your obstetrician, midwife, or registered dietitian about appropriate nutrition for your individual circumstances. This article is for educational purposes only and should not be used to make medical decisions. If you have concerns about fetal growth or nutrition during pregnancy, contact your healthcare provider immediately.