Читать книгу Genetic Disorders and the Fetus - Группа авторов - Страница 101

Disaccharidase activities in AF apparently originate from the fetal intestine and the kidney.^{130, 131, 134, 135, 137} The kidney disaccharidases (mainly trehalase) are detected in the AF at a later stage of gestation than the intestinal enzymes¹³² and in fetuses affected with renal pathologies.^{166, 167} Maltase activity of AF originates exclusively from the fetal intestine.¹⁶⁸ The amount of each disaccharidase released into the AF seems to be dictated by their relative sensitivities to proteolytic digestion in vivo.¹⁶⁸

Intestinal microvilli of fetal origin have been characterized in AF after purification by Ca²⁺ precipitation of contaminating organelles followed by differential centrifugation of the microvillar membranes.^{169, 170} In the purified preparation, the specific activities of the intestinal microvillar marker enzymes maltase and sucrase increased about 77‐fold over those in cell‐free AF. AF microvilli contain typical enzymes of intestinal microvilli, including maltase, sucrase, trehalase, alkaline phosphatase, and γ‐glutamyl transferase, and their morphology detected by electron microscopy resembles that of vesiculated intestinal microvilli. Jalanko et al.¹⁷¹ also reported the presence of vesicles in AF, which they concluded originate in the fetal intestine. Prenatal detection of genetic diseases due to a deficiency of a protein expressed in these membranes or associated with abnormal morphology of microvilli seems feasible, although such diagnoses have not been described for many years. Transport system activities expressed in these membranes can also be assayed by measuring the uptake of radioactive substrates. Na⁺‐dependent glucose transport, inhibitable by phlorizin, was demonstrated in microvilli purified from AF, suggesting that transporter systems can be assayed in these membranes (Figure 3.2). There is evidence that trehalase activity also could originate from the fetal kidney, at least in pathologic situations. Several fetuses with proven intestinal obstructions had normal trehalase activity, despite the fact that the other disaccharidases were almost completely deficient.^{166, 172, 173} In addition, high trehalase activity (relative to the other disaccharidases) was found in the AF of fetuses with renal anomalies such as polycystic kidney disease¹⁶⁶ and congenital nephrotic syndrome.¹⁷³ In their study on the origin of α‐glucosidase activity in human AF, Poenaru et al.¹⁷⁴ concluded that both renal and intestinal α‐glucosidases were present.

Figure 3.2 The uptake of ³H‐glucose in microvilli prepared from (a) fetal intestinal mucosa and (b) amniotic fluid.

Isoelectric focusing revealed that the intestinal form of trehalase (pI54.60) was present in AF samples collected before 21 weeks, whereas only the renal form (pI54.24) was present in samples obtained later in pregnancy.¹⁷⁵ In one fetus affected with polycystic kidney disease, the renal form of trehalase was markedly increased in the AF. In another fetus with intestinal obstruction, the intestinal form of trehalase, as well as other disaccharidase activities, was reduced in the AF. However, no systematic study on the clinical usefulness of AF trehalase for the detection of fetal renal anomalies has yet been conducted.