Altered Umbilical Cord Blood Nutrient Levels, Placental Cell Turnover and Transporter Expression in Human Term Pregnancies Conceived by Intracytoplasmic Sperm Injection (ICSI)

Nutrients. 2021 Jul 28;13(8):2587. doi: 10.3390/nu13082587.

Abstract

Assisted reproductive technologies (ART) may increase risk for abnormal placental development, preterm delivery and low birthweight. We investigated placental morphology, transporter expression and paired maternal/umbilical fasting blood nutrient levels in human term pregnancies conceived naturally (n = 10) or by intracytoplasmic sperm injection (ICSI; n = 11). Maternal and umbilical vein blood from singleton term (>37 weeks) C-section pregnancies were assessed for levels of free amino acids, glucose, free fatty acids (FFA), cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low-density lipoprotein (VLDL) and triglycerides. We quantified placental expression of GLUT1 (glucose), SNAT2 (amino acids), P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) (drug) transporters, and placental morphology and pathology. Following ICSI, placental SNAT2 protein expression was downregulated and umbilical cord blood levels of citrulline were increased, while FFA levels were decreased at term (p < 0.05). Placental proliferation and apoptotic rates were increased in ICSI placentae (p < 0.05). No changes in maternal blood nutrient levels, placental GLUT1, P-gp and BCRP expression, or placental histopathology were observed. In term pregnancies, ICSI impairs placental SNAT2 transporter expression and cell turnover, and alters umbilical vein levels of specific nutrients without changing placental morphology. These may represent mechanisms through which ICSI impacts pregnancy outcomes and programs disease risk trajectories in offspring across the life course.

Keywords: GLUT1; P-gp and BCRP; SNAT2; amino acids; apoptosis; assisted reproductive technology (ART); citrulline; free fatty acids (FFA); glucose; intracytoplasmic sperm injection (ICSI); lipids; placenta; proliferation.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / metabolism
  • Adult
  • Amino Acid Transport System A / metabolism
  • Apoptosis
  • Cell Proliferation
  • Female
  • Fertilization*
  • Fetal Blood / metabolism*
  • Glucose Transporter Type 1 / metabolism
  • Humans
  • Neoplasm Proteins / metabolism
  • Nutrients*
  • Placenta / metabolism*
  • Placenta / pathology
  • Pregnancy
  • Pregnancy Outcome
  • Pregnancy Trimester, Third*
  • Premature Birth / etiology
  • Reproductive Techniques, Assisted / adverse effects
  • Sperm Injections, Intracytoplasmic / adverse effects*
  • Sperm Injections, Intracytoplasmic / methods

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Amino Acid Transport System A
  • Glucose Transporter Type 1
  • Neoplasm Proteins
  • SLC2A1 protein, human
  • SLC38A2 protein, human