When pregnancies end early without a clear cause, attention often turns to maternal health. A Texas A&M team is taking a different tack by focusing on paternal epigenetics, asking how molecular information carried by sperm might influence embryo development and pregnancy loss.
Lacey Luense, an assistant professor in the Texas A&M College of Agriculture and Life Sciences Department of Animal Science and a Texas A&M AgriLife Research appointee, is studying early pregnancy loss across species. Working in cattle, where nearly half of pregnancies are estimated to fail before term, she aims to illuminate mechanisms relevant to human infertility, where more than half of conceptions are estimated not to result in birth.
Luense said maternal factors such as chromosomal abnormalities, disease, or uterine conditions are known contributors. Yet many losses remain unexplained. Her lab is partnering with Ky Pohler, administrator of the Texas A&M AgriLife Animal Reproductive Biotechnology Center and associate professor in the Department of Animal Science, on a $1.65 million National Institutes of Health grant to investigate how paternal epigenetic information, or non-genetic changes to DNA, is delivered to the embryo.
Determining the male factor in unsuccessful pregnancies
The project centers on how paternal epigenetics, meaning regulatory information beyond the DNA sequence, may shape embryo development. The team will compare sperm from bulls with high and low fertility to test how the paternal epigenome relates to abnormal embryo development and pregnancy loss.
One focus is histones, the proteins that package DNA. Prior studies have linked atypical sperm histones with a higher likelihood of pregnancy loss in partners, although the reasons remain unclear. Luense said the objective is to define how epigenetic signals in sperm influence fertility, pregnancy, and long-term health.
Cattle can answer questions humans cannot
Because experiments on human embryos are not feasible, the group is using cattle, which more closely mirror human early embryonic development than mice, particularly in cell division and the timing of embryo gene activation.
The researchers will conduct molecular and genomic analyses on semen from high- and low-performing bulls to identify biomarkers and epigenetic features that may predict pregnancy loss. Through in vitro fertilization, they will generate embryos using sperm with defined epigenetic differences, then apply time-lapse imaging and advanced genomic assays to determine whether changes to sperm histones alter development and gene regulation.
The Animal Reproductive Biotechnology Center, which opened in 2025, will enable gene editing, including CRISPR/Cas9, to advance understanding of pregnancy loss and support development of future interventions.
Luense said the team is mapping early gene expression changes in pre-implantation cattle embryos to glean insights into human pregnancy.
Biomarkers to predict, and someday prevent, pregnancy loss
Beyond implications for human health, the findings could equip cattle producers with tools to address a costly challenge, since about half of cattle pregnancies do not result in live births. Better prediction could reduce losses across the industry, complementing market insights such as those in USDA Cattle on Feed report signals firmer cattle market.
Luense said the five-year goal is to pinpoint biomarkers or alterations to sperm chromatin or histones that may predict pregnancy loss in both humans and cattle. Identifying what to look for could guide treatment strategies. Results could improve reproductive efficiency and inform clinical management for patients and livestock affected by infertility, poor embryogenesis, and pregnancy loss.
Paternal epigenetics at the core of the inquiry
The research team aims to connect specific sperm epigenetic patterns to early embryo gene regulation, providing a roadmap for future diagnostics and potential therapies that address the paternal contribution to pregnancy outcomes. The work is supported by the National Institutes of Health and is part of broader efforts in reproductive biotechnology at Texas A&M.