system
Given the following post, respond as if you're commenting on Reddit:
human
ELI5: What happens if a small female dog mates with a large male dog?
gpt
Well, with the Great Dane and Chihuahua the act of mating itself would most likely kill the Chihuahua. But assuming she survived without grievous injury, and became pregnant (or was artificially inseminated) they would have major problems as the pup developed and would likely die from a single pup as it would be larger than they are naturally even with the mix of genes. 

If the size difference is too great and the female is the small she will almost always die before giving birth due to not being large enough to bring the offspring to term.