A mule, the offspring of a female horse and a male donkey, is prized for strength and stamina, but it almost never has young of its own. The problem isn’t the mule’s body or its mating. It lies in the genetic instructions the animal inherited from two different species, which don’t match well enough to pair up when sperm or eggs are made.1Heredity. The pachytene checkpoint and its relationship to evolutionary patterns of polyploidization and hybrid sterility The barrier isn’t quite total, though, since a few female mules have given birth.
Horse and Donkey Chromosomes Don’t Add Up
Chromosomes are the packages of DNA inside every cell, and most animals carry them in matched pairs, one from each parent. A horse has 64 chromosomes and a donkey has 62.2The Tech Interactive. Why can’t mules breed? A mule inherits 32 from its horse mother and 31 from its donkey father, for a total of 63.3The Tech Interactive. Why can’t mules breed? An odd number means at least one chromosome in every mule cell has no partner at all.
In a mule, the horse set of 32 and the donkey set of 31 can’t line up one-to-one. Many horse and donkey chromosomes do have a recognizable counterpart, but the match is loose rather than exact.
The count isn’t the only difference. Horse and donkey chromosomes also differ in structure.4Revision Dojo. Why Mules Can’t Have Babies: The Biological Reason Donkey chromosomes were heavily rearranged over a short span of evolutionary time, with many pieces moved around.5PubMed Central. Phased T2T horse and donkey assemblies from a mule reveal peculiar equid centromere evolution At least five such rearrangements happened in the donkey line within roughly the last million years.6PubMed. Evolutionary movement of centromeres in horse, donkey, and zebra So even chromosomes that look like partners often carry their genes in different orders.
The odd number on its own isn’t the whole story, since some animals with odd counts still breed. The mismatch in structure shows up most when cells must line chromosomes up side by side.
A mule isn’t missing genes or carrying damaged chromosomes; it has a full working set from each parent. Ordinary body cells divide by copying every chromosome and splitting the copies, which never asks chromosomes to find partners. Muscle, skin, and organs build and repair normally, which is why mules grow, work, and live long lives. The trouble appears only in the special division that makes sperm and eggs.
Where Sperm and Egg Production Breaks Down
To make sperm or eggs, the body uses a special division that halves the chromosome number. Before the first split, each chromosome must find a similar partner and pair with it so the two can be pulled apart correctly.7Revision Dojo. Why Mules Can’t Have Babies: The Biological Reason In a mule, horse and donkey chromosomes differ too much, so pairing is incomplete or irregular.8Revision Dojo. Why Mules Can’t Have Babies: The Biological Reason
Pairing matters because paired chromosomes are pulled to opposite sides of the cell, so each sperm or egg gets exactly one copy of each. Unpaired chromosomes can be dragged to one side at random, leaving cells with missing or extra chromosomes.
Mammals have a built-in check for this. Midway through the division, the body inspects cells and destroys those whose chromosomes haven’t paired properly. In a mule, nearly every cell fails the inspection, so almost none reach maturity.
In male mules, sperm production usually doesn’t get beyond the early stage of developing sperm cells.9PubMed. Comparative testis morphometry and seminiferous epithelium cycle length in donkeys and mules The cells break down at a mid-point of meiosis where pairing is checked.10Cytogenetic and Genome Research. Meiosis in interspecific equine hybrids: I. The male mule (Equus asinus × E. caballus) and hinny (E. caballus × E. asinus) The surrounding support cells in the testis look normal,11Animal Reproduction. Ultrastructural observation of the mule testis indicates normal function of somatic cells which means the failure lies in the sperm-forming cells themselves, not the organs.
In females, the ovaries of mules and hinnies are severely depleted, with most egg cells eliminated soon after birth at the same pairing stage.12Heredity. The pachytene checkpoint and its relationship to evolutionary patterns of polyploidization and hybrid sterility The same cell-level checkpoint that destroys badly paired cells appears to remove them in both sexes.13Heredity. The pachytene checkpoint and its relationship to evolutionary patterns of polyploidization and hybrid sterility
Sterility doesn’t mean a mule lacks reproductive organs; the failure is invisible except under a microscope. A male mule can still mate and show interest in females, but without sperm, mating produces no pregnancy.
The Rare Mules That Have Had Foals
In China, a female mule and a female hinny that mated with donkeys each produced a filly, confirmed by chromosome testing.14PubMed. A fertile mule and hinny in China A mule named Kate in Colorado also gave birth to a foal, and hair and blood tests at two universities confirmed she was a mule and the mother.15NPR. Befuddling Birth: The Case of the Mule’s Foal Such births have not been reported in males.
Claimed mule births deserve suspicion. Many reported cases turn out to involve a mare adopting a foal, and only genetic testing of mother and foal settles the question.
Most horse–donkey hybrids are sterile, but the degree varies from animal to animal, on a gradual range from sterile toward fertile.16Heredity. The variety of sterility and gradual progression to fertility in hybrids of the horse and donkey Even in males, a few mature sperm have been found in a hinny.17Cytogenetic and Genome Research. Meiosis in interspecific equine hybrids: I. The male mule (Equus asinus × E. caballus) and hinny (E. caballus × E. asinus) So a female’s occasional surviving egg may carry a workable set of chromosomes.
The checkpoint destroys cells that can’t pair, so an egg survives only if it ends up with a chromosome set that doesn’t need pairing. By chance, the division can occasionally hand an egg a complete horse set or a complete donkey set. Mating that mule with a donkey or a horse then adds a matching set from the father, giving the foal a workable combination. That’s why the verified births involve females mated to donkeys, not mule-to-mule pairings. The foals from these rare births have chromosome sets unlike either the mule’s or each other’s.18PubMed. A fertile mule and hinny in China
Mules Versus Hinnies
A hinny comes from a male horse and a female donkey, the reverse of a mule.19Heredity. The pachytene checkpoint and its relationship to evolutionary patterns of polyploidization and hybrid sterility It also carries 63 chromosomes and is typically sterile for the same reason.20Heredity. The pachytene checkpoint and its relationship to evolutionary patterns of polyploidization and hybrid sterility
The two animals still differ. Some genes are switched on only from the mother’s or only the father’s copy.21PubMed. Hinny In mules, about 50 genes are used from only one parent’s copy.22unifind.unime.it. Transcriptome wide investigation of parent-of-origin expressed genes in mule (horse x donkey) by next-generation semiconductor-based sequencing Swapping parents changes which copy is active even when the DNA is the same, and the animal also develops inside a different species of mother, which shapes its early growth. This helps explain why hinnies and mules differ in looks and temperament despite inheriting the same two kinds of chromosome sets.23PubMed. Hinny
Hinnies are often a bit smaller, partly because a donkey mother is carrying them, and they tend to have more horse-like heads and shorter ears. Those are tendencies rather than a dependable test, since individual animals vary, so parentage records are the only sure answer. Mules are more common because breeders find them easier to produce.
Why Horses and Donkeys Can Mate at All
Horses, donkeys and zebras all belong to one genus, which arose about 4 to 4.5 million years ago.24PubMed Central. Speciation with gene flow in equids despite extensive chromosomal plasticity They share most of their genetic instructions because they split from a common ancestor relatively recently. That similarity is enough for an embryo to develop into a healthy body. The differences only become a barrier later, when sex cells need exact chromosome pairing.
These animals can produce first-generation hybrids despite big differences, though most are infertile.25Journal of Archaeological Science. Zonkey: A simple, accurate and sensitive pipeline to genetically identify equine F1-hybrids in archaeological assemblages Zebra hybrids such as zorses and zonkeys face the same barrier, since it comes from how different the parents’ chromosomes are. Because mules are almost always sterile, breeders must cross a horse and a donkey every time they want a mule.
The barrier isn’t perfect. Genes have still passed between equid species in the past despite chromosome counts from 16 to 31 pairs.26PubMed Central. Speciation with gene flow in equids despite extensive chromosomal plasticity
Can Science Help a Mule Reproduce
A mule has been cloned from fetal cells, copying an existing mule rather than breeding one.27PubMed. A mule cloned from fetal cells by nuclear transfer A clone is a genetic copy of one animal, not a child made from sperm and egg. It has the same 63 chromosomes and faces the same sterility.
In 2024, mule embryos were first made by injecting a single donkey sperm into a horse egg in the lab.28PubMed Central. Current and Emerging Advanced Techniques for Breeding Donkeys and Mules That shows horse and donkey genetic material can start development under controlled conditions. But it’s ordinary mule parentage, not a mule’s own offspring, and no pregnancies from such embryos have been reported yet.29PubMed Central. Current and Emerging Advanced Techniques for Breeding Donkeys and Mules Nothing so far shows one could grow into a foal.