In a quiet lab at Cornell University, scientists have made a discovery that could reshape how we think about life’s earliest stages. Researchers found that male and female embryos begin developing differently just seven to eight days after fertilization. This difference appears before sex hormones like testosterone or estrogen are even present.
For decades, scientists knew that male embryos in many mammal species—such as cows, mice, and even humans—tend to grow faster than female ones. But no one really knew why. The new study, published in the journal, Cell & Bioscience, dives deep into the genetics of this mystery and uncovers clear molecular reasons.
The team studied cow embryos in petri dishes. By examining each embryo’s RNA—tiny molecules that help turn genes into action—the researchers were able to track how genes were being expressed at this early stage. The results were striking.
Overview of embryo sex determination. (CREDIT: Cell & Bioscience)
Male embryos prioritized genes related to energy metabolism. This allowed them to grow more quickly. Female embryos, however, focused on genes related to sex differentiation, the development of reproductive organs, and inflammation, which plays a key role in immune system development.
This wasn’t just a tiny difference. The two sexes followed very different genetic “blueprints” from the very beginning. According to Jingyue “Ellie” Duan, assistant professor of functional genomics at Cornell’s College of Agriculture and Life Sciences and co-author of the study, the discovery proves that sex matters at the cellular level much earlier than most people realize.
“Sex difference has been a factor ignored in a lot of studies and clinical trials,” said Duan. “Until very recently, most mouse studies have used exclusively male mice. And most drug discovery is done with male mice.”
That oversight could be leading to gaps in understanding how diseases affect men and women differently. Conditions like Alzheimer’s, autoimmune diseases, and even heart disease often show up differently depending on biological sex. These new findings suggest those differences may begin long before birth.
Related StoriesThe Science Behind the Differences
At this stage of development, embryos have not yet developed the sex hormones that define many differences between males and females later in life. The fact that gene activity already varies suggests that something deeper is at work.
Researchers believe the answer may lie in the chromosomes themselves. Female embryos carry two X chromosomes (XX), while males carry one X and one Y (XY). These differences influence which genes are turned on or off.
“This could imply that there’s an intrinsic factor in our genome contributing to the sex-based differences we see,” said Duan. “Not just from hormonal change or environmental factors.”
In simple terms, the genes we are born with already begin guiding the future of our health and development—before our bodies even form organs. These early patterns could affect everything from how the immune system forms to how we respond to diseases decades later.
Sex-biased genes of bovine expanded blastocysts and functional enrichment. A Volcano plot showing all DEGs between male and female expanded blastocysts (BL). (CREDIT: Cell & Bioscience)
To understand these patterns, the team performed genome-wide analysis using cutting-edge RNA sequencing. This approach allowed them to look at the whole set of active genes in each embryo.
They found that male embryos had higher levels of gene activity involved in generating energy. These genes helped fuel faster cell division and quicker development.
In contrast, female embryos activated genes tied to preparing for reproductive development and building immune system components. These differences are important because they could lead to different health risks later in life.
Why Bovine Embryos Matter for Humans
Cows might not seem like the first choice for studying human health, but they’re more similar than you might think. Bovine embryos develop at a pace and pattern that closely mirrors human embryos. They also offer practical benefits. Embryos can be easily collected and studied in the lab, making them ideal for this kind of work.
Cornell’s team didn’t just pick cows by chance. Their findings could improve human in vitro fertilization (IVF) techniques. If researchers understand how male and female embryos behave differently, doctors may be able to tailor IVF methods for greater success.
Heatmaps of Sex-biased transcription regulators and genomic distribution of DEGs. (CREDIT:
“We’re born with this sex-specific genetic regulation that is contributing very differently to cellular behavior, disease onset and immune system development,” Duan said. “That continues through life all the way to health and aging.”
That’s not all. This research could also help scientists design better medications. Right now, most drugs are developed using male lab animals. That leads to medicines that don’t always work as well—or safely—for women.
By studying these early differences in gene activity, researchers can start to design treatments that consider both sexes from the beginning. That could lead to drugs that are more effective for everyone.
Impact on Agriculture and IVF
The study doesn’t just matter for people. It could also help farmers and the dairy industry.
Dairy farms rely heavily on cattle reproduction through IVF. These reproductive programs help ensure a steady supply of milk and allow for better control over herd genetics. However, IVF in cattle still has high failure rates and unpredictable outcomes.
By better understanding the genetic differences in early embryos, scientists may be able to improve the success rate of IVF in cows. This could reduce costs and improve animal health, supporting more sustainable farming.
“Understanding and optimizing bovine reproduction is especially important for the dairy industry,” Duan said.
Gene dosage compensation. The X:A expression ratio was calculated using expressed genes (TPM > 1), DEGs and non-DEGs in female and male expanded blastocysts. (CREDIT: Cell & Bioscience)
To carry out the study, Duan’s lab partnered with Soon Hon Cheong, associate professor of clinical sciences at Cornell’s College of Veterinary Medicine. Cheong’s lab focuses on reproductive medicine and assisted reproduction.
This partnership allowed the team to connect gene-level research with real-world applications in animal health and agriculture. According to Duan, the collaboration was essential. “This project would not have been possible without it,” she said.
Looking Ahead
The researchers are already continuing their work. Future studies will look at how these sex-based differences evolve over time. Instead of focusing only on day seven or eight, they plan to examine embryos continuously from fertilization through the eighth day.
This will help them map when and how the gene activity changes—and whether the early trends they’ve observed remain consistent. That could lead to even deeper insights into embryo health, development, and the earliest roots of sex-based diseases.
The project received support from the National Science Foundation and the Cornell Center for Vertebrate Genomics. It’s a strong sign that these findings are not only scientifically significant but also important for health and agriculture across the board.
Functional enrichment of sex-biased isoforms and associated genes. (CREDIT: Cell & Bioscience)
The next steps may include applying the findings in IVF clinics or developing new guidelines for drug testing that better reflect biological sex differences. Over time, this research could lead to healthier outcomes—not just for the people receiving treatments, but for entire industries that rely on reproductive science.
As this research shows, development doesn’t wait until birth to start making decisions. The body begins shaping its future within days of conception. And thanks to new tools and dedicated scientists, the world is starting to understand just how important those early choices are.