Skip to main content
ARS Home » Plains Area » Clay Center, Nebraska » U.S. Meat Animal Research Center » Livestock Bio-Systems » Research » Publications at this Location » Publication #417149
Research Project: Applying Nutritional Strategies to Improve Early Embryonic Development and Progeny Performance in Beef Cows

Location: Livestock Bio-Systems

Title: Fertility and early embryonic development in a CD46-edited Gir heifer with reduced susceptibility to BVDV

Author
item Snider, Alexandria - Alex
item Workman, Aspen
item Heaton, Michael - Mike
item VANDER LEY, BRIDAN - University Of Nebraska
item KRUEGER, ALEXANDRIA - Orise Fellow
item SONSTEGARD, TAD - Acceligen Inc

Submitted to: Biology of Reproduction
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/14/2024
Publication Date: N/A
Citation: N/A

Interpretive Summary: Reproductive failures in cattle can be due to bovine viral diarrhea virus (BVDV) infection during late pregnancy. The receptor for this virus (CD46) has been edited in a Gir heifer calf to have reduced susceptibility to BVDV. The current study investigated fertility success of the Gir heifer calf and confirmation of the CD46 edit in heterozygous blastocysts. The CD46 edit does not impair fertility of the CD46 Gir heifer and the CD46 edit was confirmed in the heterozygous blastocysts. This information confirms there is not a negative impact on female fertility due to the CD46 edit.

Technical Abstract: Bovine viral diarrhea virus (BVDV) infection during pregnancy is a significant contributor to reproductive failures in cattle. The bovine receptor for BVDV (CD46) has been precisely edited with a six amino acid substitution (G82QVLAL to A82LPTFS) and shown to have significantly reduced BVDV susceptibility in a Gir heifer calf. Since CD46 is known to play a role in mammalian fertilization, our objective here was to assess the edited heifer's fertilization rates, early embryonic development, and to confirm germline transmission of the edit. Cumulus oocyte complexes were collected from the edited heifer and unedited females and fertilized with semen from an unedited bull and cultured until the blastocyst stage. Ultrasound examinations and serum progesterone concentration were also monitored to confirm estrous cyclicity in the CD46-edited heifer. Fertilization rates and blastocyst development were not different in oocytes from edited and unedited controls. Estrous cyclicity was normal with visualization of a corpus luteum and elevated progesterone concentrations. Genome sequence analysis of two blastocysts confirmed germline transmission of either edited allele from the heifer. Subsequently, the CD46-edited heifer was artificially inseminated with semen from an unedited Gir bull and fertility status was confirmed with a diagnosed conception at day 35 of gestation. This study showed that a six amino acid substitution in CD46 did not negatively affect fertilization or early embryonic development when fertilized with semen from an unedited bull. While these results show promise, investigations also are needed with sperm cells carrying a similar CD46 edit before the full impact can be assessed.