Wolf Lab - Research

Biology and Biotechnology of Reproduction

Our research investigates the mechanisms that govern early embryonic development and pregnancy establishment in livestock, with a particular focus on cattle. Livestock offer valuable models for aspects of human reproductive biology, while reproductive biotechnologies enable targeted studies of gene function and the generation of large animal models (1).

A central focus is the maternal-to-embryonic transition, when developmental control shifts from maternal RNAs and proteins stored in the oocyte to the embryo’s own genome. Using RNA sequencing, we mapped the onset of embryonic transcription for almost 7,400 bovine genes (2). This work provides a foundation for investigating genome activation and the effects of maternal metabolism and embryo culture conditions (3). Comparative studies further reveal how genes and transposable elements are regulated during early mammalian development (4).
We combine embryo technologies with CRISPR/Cas9 gene editing to determine how key regulatory factors control pluripotency and the formation of the first embryonic cell lineages. Our studies established that OCT4/POU5F1 is required for NANOG expression and inner cell mass differentiation in bovine embryos (5,6), whereas hypoblast formation can occur without NANOG (7).

Another major research area is communication between the embryo and the maternal reproductive tract. Early pregnancy loss is a major challenge to reproductive efficiency in cattle. Our research shows that embryos lacking interferon tau (IFNT)—long considered essential for maternal recognition of pregnancy—can establish pregnancy and develop into healthy calves (8; Fig. 1). This finding challenges the established model of embryo–maternal communication and points to alternative signals, including prostaglandin E2, whose role remains to be tested. Future studies will investigate these pathways and the long-term effects of IFNT deficiency. By revealing how embryos sustain early pregnancy, this work could inform strategies to reduce reproductive losses, improve animal welfare, and support more efficient, sustainable livestock production.

Together, these studies advance our understanding of mammalian reproduction and provide a scientific basis for improving reproductive biotechnologies and developing genetically modified livestock models.

Fig. 1. Experimental Proof that IFNT is Dispensable for Pregnancy Recognition in Cattle. a) Experimental strategy; b) Day-18 conceptuses; c) Conceptus length; d) Western blot analysis of IFNT in conceptuses; e) Twin pregnancy, IFNT-KO fetuses day 49; f) IFNT-KO fetus day 75; g) IFNT-KO calves.

Funding

German Research Foundation (DFG; grant 405453332) │ Bayerische Forschungsstiftung (AZ-1031-12) │ Leducq Foundation (23CVD01)

References

1. Alberio R, Wolf E. Nuclear transfer and the development of genetically modified/gene edited livestock. Reproduction. 2021;162(1)–F68. doi:10.1530/REP-21-0078.
2. Graf A, et al. Fine mapping of genome activation in bovine embryos by RNA sequencing. Proceedings of the National Academy of Sciences USA. 2014;111(11):4139–4144. doi:10.1073/pnas.1321569111.
3. Rabaglino MB, et al. Maternal metabolic status and in-vitro culture conditions during embryonic genome activation deregulate the expression of energy-related genes in the bovine 16-cells embryo. PLOS ONE. 2023;18(8). doi:10.1371/journal.pone.0290689.
4. Oomen ME, et al. An atlas of transcription initiation reveals regulatory principles of gene and transposable element expression in early mammalian development. Cell. 2025;188(4):1156–1174.e20. doi:10.1016/j.cell.2024.12.013.
5. Simmet K, et al. OCT4/POU5F1 is required for NANOG expression in bovine blastocysts. Proceedings of the National Academy of Sciences USA. 2018;115(11):2770–2775. doi:10.1073/pnas.1718833115.
6. Simmet K, et al. OCT4/POU5F1 is indispensable for the lineage differentiation of the inner cell mass in bovine embryos. FASEB Journal. 2022;36(6). doi:10.1096/fj.202101713RRR.
7. Springer C, Zakhartchenko V, Wolf E, Simmet K. Hypoblast formation in bovine embryos does not depend on NANOG. Cells. 2021;10(9):2232. doi:10.3390/cells10092232.
8. Ali A, et al. Pregnancy establishment in cattle without embryonic interferon tau. Nature Communications. 2026;17:10609. doi:10.1038/s41467-026-78446-4.