HUADE INSIGHTS | Receptors Responded — So Why Didn't the Chicks Grow Better?

Reference 

Kim E, Akhtar N, Li J, et al. In ovo feeding of epidermal growth factor: embryonic expression of intestinal epidermal growth factor receptor and posthatch growth performance and intestinal development in broiler chickens. Poultry Science, 2020, 99: 5736–5743. 

Statement

This article is a translated and condensed summary based on the above review article. The content has been reorganized for scientific communication and educational purposes and does not represent the complete views of the original publication. Readers are encouraged to consult the original article for comprehensive information.

In our previous article, we showed that EGF did indeed "awaken" receptors in the embryonic chicken intestine — but this response didn't emerge until hatch day. At this point in the story, many would assume the outcome should follow naturally: the signal was present, the receptor responded, and improved growth performance should logically follow.

However, after the research team reared the chicks for a further 21 days, they found that the key production parameters — body weight, feed intake, feed conversion ratio (FCR), intestinal weight, and villus height — showed almost no statistically significant differences. The signal was clearly present, but the expected outcome failed to materialize. To many, this might suggest that "EGF doesn't work." But to those working in R&D, this is precisely where the real question begins. Rather than stopping here, the research team proposed several possible explanations. On the surface, these explanations pertain specifically to EGF — but in reality, they reflect a challenge common to the development of all bioactive functional substances.

Challenge One: Can It Actually Reach the Intestine?

EGF is a bioactive protein, and the defining characteristic of proteins is their susceptibility to degradation. Although the chicken embryo swallows amniotic fluid, this fluid is by no means a static, gentle environment. The researchers cite relevant literature indicating that protease activity in the amniotic fluid progressively increases as embryonic development proceeds — meaning that EGF may already be partially or even completely broken down before it is ever ingested by the embryo. Even if it fortunately makes it into the digestive tract, it must then contend with further degradation by pepsin and trypsin. For a small protein molecule consisting of only 53 amino acids, biological activity is liable to decline further with each barrier it crosses. This raises a very practical concern: the dose researchers administered by injection does not necessarily equal the dose that actually reaches the intestine.

Challenge Two: Does the Chicken Actually Recognize Porcine EGF?

This study used porcine-derived EGF (Porcine EGF). In theory, both chickens and pigs possess EGF receptors, but receptor structures are not entirely conserved across species. The paper notes that the sequence similarity in the key binding domain of the EGFR between humans and chickens is approximately 75% — a figure that indicates a certain degree of homology, but also implies potential differences in ligand-binding efficiency. For growth factors, such cross-species differences are not always merely marginal; they can directly compromise binding efficiency. In other words: EGF may have arrived, and the receptor may be present, but the two may not necessarily achieve optimal binding.

Challenge Three: Is a Single Signal Sufficient?

There is another explanation equally worth considering. EGF is not an ordinary nutrient — it functions more like a growth signal that continuously regulates cellular behavior. Yet in this study, supplementation was administered only once, in ovo, during incubation. The research team also noted that in a separate prior study, continuous EGF supplementation via feed yielded more favorable results under certain conditions. This suggests that what truly drives intestinal development may not be a brief, transient stimulus, but rather a sustained biological signal. If intestinal development is likened to constructing a house, a single supplementation is akin to a single truckload of bricks delivered on day one — what actually determines whether the house gets built is the sustained construction work carried out over the following weeks.

HUADE Technical Observations

What's most noteworthy about this paper is not that it "failed to achieve the desired outcome," but that the research team did not stop at the results themselves — they continued to probe the underlying "why." Today, an increasing number of functional products come with well-defined mechanisms of action, yet relatively few can be reliably and consistently applied at the production level. The reason is often not a flawed mechanism, but rather unresolved challenges spanning delivery method, window of action, bioavailability, and application context. This is precisely why, whenever we evaluate whether a given raw material can truly be translated into practical application, we make a habit of asking a further set of questions: Can it actually be delivered to the target site? Can it be accurately recognized? And is exposure sustained for long enough? A validated mechanism of action is only the first step.