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

Accepted version
Peer-reviewed

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Article

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Authors

Salazar-Petres, Esteban 
Carvalho, Daniela Pereira 
Lopez-Tello, Jorge 
Sferruzzi-Perri, Amanda Nancy 

Abstract

Fetal growth depends on placental function, which requires energy from mitochondria. Here we investigated whether mitochondrial function in the placenta relates to the 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), mitochondrial regulators, nutrient transporters, hormone handling, and signaling 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. In addition, placental morphology and steroidogenic gene (Cyp17a1 and Cyp11a1) expression were aberrant for the lightest females, but glucose transporter (Slc2a1) expression was lower in only the lightest males versus their heaviest counterparts. Differences in intra-litter placental phenotype were related to changes in the expression of hormone-responsive (androgen receptor) and metabolic signaling (AMPK, AKT, and PPARγ) pathways. Thus, in normal mouse pregnancy, placental structure, function, and mitochondrial phenotype are differentially responsive to the growth of the female and 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.

Description

Keywords

3215 Reproductive Medicine, 32 Biomedical and Clinical Sciences, 31 Biological Sciences, Pregnancy, Genetics, Contraception/Reproduction, Pediatric, Women's Health, 1.1 Normal biological development and functioning, Reproductive health and childbirth

Journal Title

Biology of Reproduction

Conference Name

Journal ISSN

0006-3363

Volume Title

Publisher

Society for the Study of Reproduction
Sponsorship
Wellcome Trust (220456/Z/20/Z)
Medical Research Council (MR/R022690/1)