Placental structure, function and mitochondrial phenotype relate to fetal size and sex in mice

Abstract

Fetal growth depends on placental function, which requires energy supplied by mitochondria. Here we investigated whether mitochondrial function in the placenta relates to growth of the lightest and heaviest fetuses of each sex within the litter of mice. Placentas from the lightest and heaviest fetuses were taken to evaluate placenta morphology (stereology), mitochondrial energetics (high-resolution respirometry), and mitochondrial regulators, nutrient transporters, hormone handling and signalling pathways (qPCR and western blotting). We found that mitochondrial complex I and II oxygen consumption rate was greater for placentas supporting the lightest female fetuses, although placental complex I abundance of the lightest females and complexes III and V of the lightest males were decreased compared to their heaviest counterparts. Expression of mitochondrial biogenesis (Nrf1) and fission (Drp1 and Fis1) genes was lower in the placenta from the lightest females, whilst biogenesis-related gene Tfam was greater in the placenta of the lightest male fetuses. Additionally, placental morphology and steroidogenic gene (Cyp17a1 and Cyp11a1) expression were aberrant for the lightest females, but glucose transporter (Glut1) expression lower in only the lightest males versus their heaviest counterparts. Differences in intra-litter placental phenotype were related to sex-dependent changes in the expression of hormone responsive (androgen receptor) and metabolic signalling pathways (AMPK, AKT, PPARγ). Thus, in normal mouse pregnancy, placental structure, function and mitochondrial phenotype are differentially responsive to growth of the female and the male fetus. This study may inform the design of sex-specific therapies for placental insufficiency and fetal growth abnormalities with life-long benefits for the offspring.

Are there sex differences in fetal growth strategies and in the long-term effects of pregnancy complications on cognitive functioning?

“…However, it remains possible that differences in placental structure and function could lead to sex differences in the ability of the placenta to respond to adverse conditions such as reduced nutrient supply. 23,62 Prediction 2: There will be a greater sex difference in birthweight among infants that die prenatally or shortly after birth…”

Maternal gut microbiota Bifidobacterium promotes placental morphogenesis, nutrient transport and fetal growth in mice

“…Protein extraction was performed with RIPA buffer as described previously [25]. Lysates were separated by SDS-PAGE and incubated with antibodies against p-MAPK (Thr202/Tyr204) (Cell Signalling, 4370; 1/1000), t-MAPK 44/42 (Cell Signalling, 4695; 1/1000), DLK-1 antibody (Abcam, ab21682; 1/1000), p-P38MAPK (Cell Signalling, 4511; 1/1000) and t-P38MAPK (Cell Signalling, 8690; 1/1000).…”