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

Abstract

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.

Attenuated glucose-stimulated insulin secretion during an acute IGF-1 LR3 infusion into fetal sheep does not persist in isolated islets

“…Our study was also not powered to detect sex differences. While prior fetal sheep studies have not detected sex differences in glucose-insulin responsiveness, β-cell mass, or plasma basal insulin or IGF-1 concentrations 6,36 , this deserves further investigation. Additionally, studies are needed to evaluate the contribution of neurovascular networks and other in vivo factors that may influence fetal insulin secretion.…”

“…Common pregnancy complications impacting nutrient transfer to the fetus and resulting in fetal overgrowth or growth restriction are characterized by high or low cord blood concentrations, respectively, of insulin and IGF-1 [3][4][5] . IGF-1 is more strongly correlated with fetal weight than insulin 4,6,7 . Fittingly, IGF-1 has been studied in sheep as a fetal intervention for growth restriction [8][9][10] .…”

Acute Fetal Metabolomic Changes in Twins Undergoing Fetoscopic Surgery for Twin-Twin Transfusion Syndrome

“…This would imply a depletion of normal energy usage pathways and use of alternative metabolic pathways for fetal energy as glucose, lactate and amnio-acids are all major sources of fetal nutrition (Kyllo et al, 2023). In states of impaired fetal oxygenation, such as placental insufficiency, the consumption of these energy sources change, with an overall decrease in glucose and an increase in lactate (Brown et al, 2022;Cetin et al, 2020;Thorn et al, 2013). Further, in states of fetal hypoxemia or significant stress, there is a consumption of available glucose.…”

A Two-Week Insulin Infusion in Intrauterine Growth Restricted Fetal Sheep at 75% Gestation Increases Skeletal Myoblast Replication but Did Not Restore Muscle Mass or Increase Fiber Number

“…Further investigation is required to determine whether fetal sex is a significant contributing factor in the regulation of fetal myocyte proliferation and maturation. We have recently found that in the late gestation fetal sheep, with and without placental insufficiency, fetal sex does not influence placental AA transfer or blood flow ( 54 ).…”