Asymmetric growth-limiting development of the female conceptus

Consuelo Amor S Estrella; Kathryn L Gatford; Ruidong Xiang; Ali Javadmanesh; Mani Ghanipoor-Samami; Greg S Nattrass; Entesar Shuaib; Milton M McAllister; Ian Beckman; Dana A Thomsen; Vicki L Clifton; Julie A Owens; Claire T Roberts; Stefan Hiendleder; Karen L Kind

doi:10.3389/fendo.2023.1306513

Asymmetric growth-limiting development of the female conceptus

Front Endocrinol (Lausanne). 2024 Feb 1:14:1306513. doi: 10.3389/fendo.2023.1306513. eCollection 2023.

Authors

Consuelo Amor S Estrella^{1

2}, Kathryn L Gatford^{1

3}, Ruidong Xiang^{1

2}, Ali Javadmanesh^{1

2}, Mani Ghanipoor-Samami^{1

2}, Greg S Nattrass⁴, Entesar Shuaib^{1

2}, Milton M McAllister⁵, Ian Beckman⁵, Dana A Thomsen^{1

2}, Vicki L Clifton^{1

6}, Julie A Owens^{1

7}, Claire T Roberts^{1

8}, Stefan Hiendleder^{1

2}, Karen L Kind^{1

2}

Affiliations

¹ Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia.
² Epigenetics and Genetics Group and Davies Research Centre, School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, SA, Australia.
³ School of Biomedicine, The University of Adelaide, Adelaide, SA, Australia.
⁴ South Australian Research and Development Institute, Livestock Systems, Roseworthy, SA, Australia.
⁵ School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, SA, Australia.
⁶ Mater Research Institute, University of Queensland, Brisbane, QLD, Australia.
⁷ Deakin University, Geelong, VIC, Australia.
⁸ Flinders University, College of Medicine and Public Health, Adelaide, SA, Australia.

Abstract

Introduction: Sex differences in prenatal growth may contribute to sex-dependent programming effects on postnatal phenotype.

Methods: We integrated for the first time phenotypic, histomorphological, clinico-chemical, endocrine and gene expression analyses in a single species, the bovine conceptus at mid-gestation.

Results: We demonstrate that by mid-gestation, before the onset of accelerated growth, the female conceptus displays asymmetric lower growth compared to males. Female fetuses were smaller with lower ponderal index and organ weights than males. However, their brain:body weight, brain:liver weight and heart:body weight ratios were higher than in males, indicating brain and heart 'sparing'. The female placenta weighed less and had lower volumes of trophoblast and fetal connective tissue than the male placenta. Female umbilical cord vessel diameters were smaller, and female-specific relationships of body weight and brain:liver weight ratios with cord vessel diameters indicated that the umbilico-placental vascular system creates a growth-limiting environment where blood flow is redistributed to protect brain and heart growth. Clinico-chemical indicators of liver perfusion support this female-specific growth-limiting phenotype, while lower insulin-like growth factor 2 (IGF2) gene expression in brain and heart, and lower circulating IGF2, implicate female-specific modulation of key endocrine mediators by nutrient supply.

Conclusion: This mode of female development may increase resilience to environmental perturbations in utero and contribute to sex-bias in programming outcomes including susceptibility to non-communicable diseases.

Keywords: IGF system; asymmetric growth; clinico-chemical screen; conceptus; histomorphology; sex differences; uncomplicated pregnancy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Body Weight
Cattle
Female
Fetus*
Liver
Male
Placenta* / metabolism
Pregnancy
Trophoblasts

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded by the Davies Bequest, University of Adelaide. CE received an Australia Awards Scholarship provided by the Australian Government and RX received a scholarship from the University of Adelaide. AJ and MG-S received PhD Scholarships from the Iranian Ministry of Science, Research and Technology. ES received a PhD Scholarship from the Libyan Ministry of Higher Education and Scientific Research. CR and VC were supported by NHMRC Senior Research Fellowships (CR GNT1020749, VC APP1041918), and CR is currently supported by a NHMRC Investigator Grant (GNT1174971) and a Matthew Flinders Fellowship from Flinders University. SH was a JS Davies Professorial Fellow.