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. 2021 Dec 8;33(5):581–598. doi: 10.1515/jbcpp-2021-0312

Table 4:

Gastrointestinal system, hepatic enzymes and transporter changes during normal pregnancy.

Gastrointestinal changes Direction and magnitude of change in pregnancy

  • Transporter changes in the gut

  • ABC

  • BCRP

  • GLUT2

  • MDR1 (P-gp)

  • MRP1

  • MRP2

  • MRP3

  • OST alpha

  • OST beta

  • CYP3A4

  • CYP3A5

 Decreased [122]
Increased BRCP expression in pregnant mice (30–55%) [123]
GLUT2 is increased during pregnancy
Increased expression of P-gp in pregnant mice [120]
Decreased MRP1 expression in pregnant mice (30–40%) [123]
Decreased MRP2 expression in pregnant mice (30–40%) [123]
Decreased expression of MRP3 in pregnant mice
No change in OSTα expression [123]
No change/minimal increase in OSTβ expression [123]
No change in expression of intestinal CYP3A4 [120, 124]
No change in expression of intestinal CYP3A5 [120, 124]
Hepatic changes Direction and magnitude of change in pregnancy

  • CYP expression in the liver

  • CYP1A2

  • CYP2B6

  • CYP2C9

  • CYP2C19

  • CYP2D6

  • CYP2E16

  • CYP3A3

  • CYP3A4

  • CYP3A5

  • CYP3A7

  • UGT activity

  • Cathepsin A

  • Carboxyesterase type 1 (CES1)

  • Hepato-biliary transporter changes

  • ABCG5

  • ABCG8

  • ATP8B1

  • BRCP (ABCG2)

  • BSEP – Bile salt export pump

  • ENT1

  • ENT2

  • MATE1

  • MDR3

  • MRP1

  • MRP2 (ABCC2) – Bile acid transporter

  • MRP3 (ABCB4) – Bile acid transporter

  • MRP4 – Bile acid transporter

  • MRP6

  • OAT2

  • OAT7

  • OATP1B1

  • OATP1B2

  • OATP1B3

  • OATP2B1

  • OCT1

  • OST – Bile acid transporter

  • P-gp (MRD1)

 Decrease in CYP1A2 during pregnancy [94]
Increases
Increases
Decrease in CYP2C19 during pregnancy
Increases in CYP2D6 during pregnancy [94]
Increases
Increases [94]
Increases [94]
Increases [94]
Increases [94]
Increases [125]
Expression of cathepsin A increase during pregnancy [17]
Expression of CES1 is unchanged during pregnancy [18]
>50% decrease in expression of ABCG5 in hepatocytes of pregnant mice [88]

>50% decrease in expression of ABCG8 in hepatocytes of pregnant mice [88]
ATP8B1 decrease in pregnant mice [88] and women with cholestasis [126]
Decreased expression in hepatocytes of pregnant mice [88]
Decreases expression of BSEP in hepatocytes of pregnant mice [88]
>50% decreased expression of ENT1 in pregnant mice [88]
Decreased expression of ENT2 in pregnancy
Decreased expression in pregnant mice [88]
Bile acid transporter (MDR3)
Unchanged in hepatocytes of pregnant rats [127]
Decreased expression of MRP2 in biliary system of pregnant rats [119].
50% decreased expression of MRP3 in hepatocytes of pregnant rats [127]
63% increased expression of MRP4 in hepatocytes of pregnant rats [88]
60% decreased expression of MRP6 in hepatocytes of pregnant rats [127]
70% increased expression of OAT2 in hepatocytes of pregnant mice [88]
OAT7 is only found in the liver (hepatic specific).
Relatively unchanged of OATP1B1 in hepatocytes of pregnant rats and humans [19, 127]
50% decreased expression of OATP1B2 in hepatocytes of pregnant rats [127]
Decreased expression of OAT1B3 in pregnant women with cholestasis [19]
Decreased expression of OATP2B1 in hepatocytes of pregnant mice [88]
>50% decreased expression of OCT1 in hepatocytes of mice [88]
Decreased expression of OST (alpha and beta) during pregnancy
Unchanged MRD1 expression in the liver [120]

ABC, ATP binding cassette; ABCG, ATP-binding cassette super-family G; BCRP, Breast cancer receptor protein; CYP, cytochrome P450; ENT, equilibrative nucleoside transporters; GLUT, glucose transporter; MATE, Multiantimicrobial extrusion protein; MDR, multi-drug resistance mutation, MRP, multidrug resistance protein; OAT, organic anionic transporter; OCT, organic cationic transporter; OST, Organic solute and steroid transporter; UGT, uridine 5′-diphospho-glucuronosyltransferase.