A designer network coordinating bovine artificial insemination by ovulation-triggered release of implanted sperms.
Synthetic biology has been successfully used to program novel metabolic function in mammalian cells and to design the first-generation of prosthetic networks that have shown the potential for the treatment of obesity, hormone-related disorders and hyperuricemia in small-animal model systems. By functionally rewiring luteinizing hormone receptor signaling to CREB1 (cAMP-responsive element binding protein 1)-mediated transgene expression via the common cyclic adenosine monophosphate (cAMP) second messenger pool we have designed an artificial insemination device which enables lutropin-triggered in-utero release of sperms protected inside cellulose-based implants. Swiss dairy cows treated with such in-utero implants containing spermatozoa and mammalian cells transgenic for luteinizing hormone receptor and CREB1-inducible expression of an engineered cellulase showed ovulation-triggered implant degradation and sperm release leading to successful fertilization of the animals. Synthetic devices plugged into endogenous control circuitry enable the body to automatically control spatio-temporal metabolic activities that could improve the economics of cattle breeding and provide novel opportunities for future therapeutic interventions.
Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
Christian
C
Kemmer
David Andreas
DA
Fluri
Ulrich
U
Witschi
Alain
A
Passeraub
Andreas
A
Gutzwiller
Martin
M
Fussenegger
D000818:Animals; D002417:Cattle; D002460:Cell Line; D018914:Cells, Immobilized / Q000166:cytology; D002480:Cellulase / Q000378:metabolism; D002482:Cellulose / Q000378:metabolism; D005260:Female; D005306:Fertilization; D006801:Humans; D007315:Insemination, Artificial / Q000295:instrumentation* / Q000662:veterinary*; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D010060:Ovulation; D019736:Prostheses and Implants; D013094:Spermatozoa / Q000166:cytology*; D058615:Synthetic Biology
D007986:Luteinizing Hormone; D002482:Cellulose; D002480:Cellulase