Fetal Sex Does Not Impact Placental Blood Flow or Placental Amino Acid Transfer in Late Gestation Pregnant Sheep With or Without Placental Insufficiency

Reprod Sci. 2022 Jun;29(6):1776-1789. doi: 10.1007/s43032-021-00750-9. Epub 2021 Oct 5.


Pregnant sheep have been used to model complications of human pregnancies including placental insufficiency and intrauterine growth restriction. Some of the hallmarks of placental insufficiency are slower uterine and umbilical blood flow rates, impaired placental transport of oxygen and amino acids, and lower fetal arterial concentrations of anabolic growth factors. An impact of fetal sex on these outcomes has not been identified in either human or sheep pregnancies. This is likely because most studies measuring these outcomes have used small numbers of subjects or animals. We undertook a secondary analysis of previously published data generated by our laboratory in late-gestation (gestational age of 133 ± 0 days gestational age) control sheep (n = 29 male fetuses; n = 26 female fetuses; n = 3 sex not recorded) and sheep exposed to elevated ambient temperatures to cause experimental placental insufficiency (n = 23 male fetuses; n = 17 female fetuses; n = 1 sex not recorded). The primary goal was to determine how fetal sex modifies the effect of the experimental insult on outcomes related to placental blood flow, amino acid and oxygen transport, and fetal hormones. Of the 112 outcomes measured, we only found an interaction between fetal sex and experimental insult for the uterine uptake rates of isoleucine, phenylalanine, and arginine. Additionally, most outcomes measured did not show a difference based on fetal sex when adjusting for the impact of placental insufficiency. Exceptions included fetal norepinephrine and cortisol concentrations, which were higher in female compared to male fetuses. For the parameters measured in the current analysis, the impact of fetal sex was not widespread.

Keywords: Fetus; Intrauterine growth restriction; Placenta; Sex differences; Sheep.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acids / metabolism
  • Amino Acids / pharmacology
  • Animals
  • Female
  • Fetal Growth Retardation / metabolism
  • Fetus / metabolism
  • Humans
  • Male
  • Oxygen
  • Placenta / metabolism
  • Placental Circulation
  • Placental Insufficiency* / metabolism
  • Pregnancy
  • Sheep


  • Amino Acids
  • Oxygen