Loss of Placental P-Glycoprotein May Be a Common Pathophysiologic Pathway for First Trimester Spontaneous Miscarriages

Sonali Lanjewar, Rajeswari Jayakumar, Constantine A. Axiotis

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Introduction: P-glycoprotein the highly conserved mammalian adenosine triphosphate-binding cassette transmembrane multidrug protein transporter is involved in peri-implantation events and fetal placental development. Greater expression in early versus late pregnancy and localization in both syncytio- and cytotrophoblast indicate that P-glycoprotein transports substances across the uterine epithelium during early pregnancy and protects the conceptus from toxic substances during implantation and early embryogenesis. We hypothesized that P-glycoprotein is involved in the physiologic maintenance of early pregnancy and that P-glycoprotein dysregulation may be involved in early pregnancy pathologies. Methods: First trimester dilation and curettage specimens were selected retrospectively from the archives of the Department of Pathology from spontaneous miscarriages (n = 36) and elective termination of pregnancy (n = 20). Two P-glycoprotein specific monoclonal antibodies JSB1and C219 were used on formalin-fixed, paraffin-embedded 5µ tissue sections. The location, intensity, and percentage of P-glycoprotein chorionic villous immunostaining were semiquantitated. Results: Spontaneous miscarriages demonstrated absence or significant reduction in P-glycoprotein compared to elective terminations; 75% (27/36) showed total absence of P-glycoprotein, 19% (7/36) showed only rare villi with discontinuous immunostaining, and 6% (2/36) showed weak immunostaining. In contrast, 90% of elective terminations (18/20) showed positive immunostaining for P-glycoprotein and only 10% (2/20) showed loss of P-glycoprotein expression (P <.0001). Discussion: We report a dramatic loss/decrease of P-glycoprotein in first trimester spontaneous miscarriages. This finding in conjunction with the known high expression of P-glycoprotein in normal first trimester placental tissues suggests an important role of P-glycoprotein in the maintenance of early pregnancy.

Original languageEnglish (US)
Pages (from-to)456-460
Number of pages5
JournalPediatric and Developmental Pathology
Issue number5
StatePublished - Oct 1 2019
Externally publishedYes


  • early pregnancy
  • first trimester spontaneous miscarriage
  • P-glycoprotein
  • placental adenosine triphosphate-binding cassette transporters

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pathology and Forensic Medicine


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