What metabolic activities are performed by a developing human fetus's liver?

Question

I understand that organ function varies with the stages of development. Does a fetal liver EVER perform lipogenesis, gluconeogenesis, make bile, etc? Or does it only begin performing these actions postnatally?

I have heard that a fetus delivered between 24-26 weeks can potentially be "okay" with proper care and monitoring in a hospital. I would assume (please correct me if I'm wrong) that this implies the fetus's liver has developed at this time. So in the case of a fetus that was not delivered at 24-26 weeks, does it spend the remainder of the pregnancy in a fully functioning state? Or at least, which functions does it begin to perform?

I've been trying to find an answer on Google, but one walks a fine line when searching for human development information -- either the results are oversimplified "expecting mothers" websites, or journal articles speculating about the effect of X on the development of Y in the mouse/chick/zebrafish/giraffe/et cetera other nonhuman model.

Answer 1

It's old and I can't get access to this issue of the Annals of the New York Academy of Science, but it looks like it has some relevant information. Sifting through the abstracts it seems the vasculature of the fetal liver is completed at around 8 weeks although is still different to the adult vasculature because of the umbilical vein. The growth of the organ itself goes through different stages with each lobe growing different amounts:

• They start the same size
• 12 weeks the left lobe is twice as large as the right
• 36 weeks the left is 10% larger than the right
• at birth they are the same size
• 5days after birth the right is 10% larger
• adults, they are the same size

And, studies have been conducted with dyes to look at liver function in both its capacity to concentrate the dyes and secrete it into the bile. The fetal liver can carry out bile acid synthesis, despite lacking digestive purposes, from very early on (Suchy et al. 1987). The fetus does however require help in removing the toxic cholephilic organic anions (COAs), which is done via the placenta. This review describes more.

There is also evidence to suggest the newborn's liver is not performing all the usual metabolic processes of children or adults (from looking at drug toxicity and delays in excretion/detoxification), as would be expected. More recent literature notes the fetal liver lobes (right and left) as having differnt biochemical capacities and independent function due to the right one getting less oxygen. Also, a layer of drug metabolising enzymes normally present in adults is missing in the fetal liver, although its capacity for drug metabolism is still better than that of rodents.

In the adult liver, there is a clear zonation of metabolism of carbohydrates, proteins, lipids, and bile salts. In the livers of fetal rats, mice, and humans, this heterogeneous distribution of enzymes and metabolic function does not exist initially. Towards the end of gestation, the adult pattern of heterogeneity for these processes begins to emerge, and after birth, the adult pattern is rapidly established (Ring et al. 1999)

There is in vitro evidence for the activity of glutathione S-transferase and sulfotransferases in the human fetal liver. Returning to the asymmetry of fetal liver function (albeit in sheep..) it was found that levels of malondialdehyde, an index of lipid peroxidation, oxygen consumption, and CYP levels (a family of oxidative enzymes), are higher in the left lobe than the right lobe of the fetal liver which evens out after birth.

So in conclusion, looks like a variety of metabolic enzymes are present in the human fetal liver from very early on after the organ is formed. We know a varitey of metabolic enzymes are present and the drug/dye metabolism studies show there is some fetal liver activity, albeit reduced from that of an adult or child. The limitation with many of the studies that have been done is that they have to use in vitro data and extrapolate to the in vivo situation, so I guess we still don't really know for sure how metabolically active it is. It is clear though that it remains inefficient and unable to carry out all the functions required of it during childhood/adulthood until after further development after birth when it has stopped growing and adapted to ex utero conditions.

References

Ring JA, Ghabrial H, Ching MS, Smallwood RA, Morgan DJ. Fetal hepatic drug elimination. Pharmacol Ther. 1999 Dec;84(3):429-45.

Suchy FJ, Bucuvalas JC, Novak DA. Determinants of bile formation during development: Ontogeny of hepatic bile acid metabolism and transport. Semin Liver Dis 1987; 7(2): 77-84

Answer 2

I found that a search through Google Books was helpful...

While without the excretion of feces, it might seem as if the liver would not be active, but the liver tissue is not only active in development and tissue generation but serves direct physiological function as well.

After initial phases of development, the liver produces fetal red blood cells which is normally a function carried out by specialized bone marrow hematopoietic cells. Over the course of fetal development the liver develops its typical functions. It breaks down old red blood cells and stores their iron, and pushes the waste bilins and other waste products to the umbilical cord to keep the fetus clean. The liver also synthesizes and stores fats.