Cornell researchers have uncovered the genetic triggers that cause male and female bovine embryos to develop differently, as early as seven to eight days after fertilization. This breakthrough in basic science holds significant implications for human health, particularly in areas such as drug development and in vitro fertilization (IVF), as well as for bovine health and the sustainability of the dairy industry.
Since the 1990s, scientists have known that male embryos of multiple mammalian species, including humans, grow faster than female embryos. However, the underlying reasons for this discrepancy remained unclear until now. In a new study published on August 27 in Cell & Bioscience, Cornell scientists grew bovine embryos in petri dishes and analyzed their genetic sex and RNA sequencing, revealing how genes are expressed. They discovered significant sex differences in gene regulation: male embryos prioritized genes associated with energy metabolism, causing them to grow faster, while female embryos emphasized genes linked to sex differentiation, gonad development, and inflammatory pathways crucial for future development.
Implications for Human and Bovine Health
Understanding these fundamental sex differences at the genomic and molecular levels is critically important for improving IVF success in both humans and cows, and for developing treatments effective for both men and women. Jingyue “Ellie” Duan, assistant professor of functional genomics in the College of Agriculture and Life Sciences and co-author of the paper, emphasized the importance of recognizing sex differences in scientific research.
“Sex difference has been a factor ignored in a lot of studies and clinical trials. Until very recently, most mouse studies have used exclusively male mice. And most drug discovery is done with male mice,” Duan said. “And yet, we see that onset and occurrence of many diseases are different in men and women: Alzheimer’s, autoimmune diseases, heart disease. In this basic study, we found that male and female embryos are different, even at this very early stage, on the basis of genome regulation.”
At this early stage, sex-associated hormones like estrogen and testosterone have not yet influenced development. Advances in genome sequencing technology have enabled researchers to explore these differences at a genome-wide level.
Intrinsic Genetic Factors
Duan suggests that intrinsic genetic factors, such as sex chromosomes (XX versus XY) or sex-linked genes, may contribute to these sex-based differences, beyond hormonal changes or environmental factors.
“This could imply that there’s an intrinsic factor in our genome contributing to the sex-based differences we see,” Duan said. “We’re born with this sex-specific genetic regulation that is contributing very differently to cellular behavior, disease onset and immune system development, and continues through life all the way to health and aging. That’s a very important message for people in the clinical field and people developing drugs to understand.”
Bovines serve as an effective animal model for human-health studies, but bovine research is also crucial for supporting food supplies and sustainable agriculture. Understanding and optimizing bovine reproduction is particularly important for the dairy industry, which relies on cattle reproduction through IVF to maintain milk supplies.
Collaborative Efforts and Future Research
Duan’s lab collaborated with the lab of Soon Hon Cheong, Ph.D. ’12, associate professor of clinical sciences in the College of Veterinary Medicine. This collaboration between Duan’s genomics-focused lab and Cheong’s group, which studies reproductive medicine and assisted reproductive techniques, was essential for the project’s success.
Future research, already underway in both labs, aims to expand on this work by studying sex differences in embryos from fertilization through day eight after fertilization. This research was supported by the National Science Foundation and the Cornell Center for Vertebrate Genomics.
The findings from this study not only enhance our understanding of embryonic development but also pave the way for more personalized approaches in medical treatments and agricultural practices. As research continues, the potential for significant advancements in both human health and agricultural sustainability appears promising.
