The molecular and cellular effects of maternal dietary intervention on fetal development

Lund, Emma Frances (2020) The molecular and cellular effects of maternal dietary intervention on fetal development. PhD thesis, University of Nottingham.

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Previous studies have provided a basis of knowledge of The Developmental Origins of Health and Disease (DOHaD), and the effects of maternal dietary protein during early gestation on fetal gene expression and development. Dietary protein is an essential macronutrient during pregnancy as it supports fetal growth.

Insufficient levels of maternal dietary protein may lead to sub-optimal growth and development of offspring. In beef production, the effects of low maternal dietary protein on the placentome, and the fetal mammary gland are not fully understood. The aims of the current study were to investigate the effects of maternal dietary protein on fetal gene expression and development in the mammary gland, and protein localisation in the bovine placentome.

Twelve-month-old Santa Gertrudis heifers were individually fed either low (L) (9% crude protein (CP) or high (H) (14.6% CP) protein during periconception (60 days preconception to 23 days postconception (dpc). At 23 dpc, heifers were split equally and either entered the low (7.6% CP) or high (12.4% CP) protein diet during postconception (23 dpc until the end of the first trimester, 98 dpc) in a 2x2 factorial design, yielding four maternal dietary interventions (HH, HL, LH and LL). At 98 dpc n=48 heifers were culled and placentomes and female fetal mammary tissues (n=20) were collected for analysis. At term, cotyledons were collected for analysis. Bovine fetal mammary tissues (n=4 per fetus) were designated for RNA-seq (n=2 per fetus) or histological (n=2 per fetus) analysis. The current study investigated placentomes and term cotyledons via immunohistochemistry.

To our knowledge this is the first study to quantify parenchymal structures and produce transcriptomic data of the bovine fetal mammary gland at 98 dpc. Total mammary epithelial and collagen area was unaffected by maternal diet (p>0.05). Duct lumen size was 45.9% greater in tissues exposed to HPost versus LPost (p<0.05). Fetal mammary stromal blood vessel number was 59% greater (p<0.05) in tissues exposed to LPeri (9% CP), versus HPeri (14.6% CP). Transcriptomics analysis of (n=2) LH and (n=2) HH exposed mammary tissues indicated up-regulation of 45 genes related to immune function, and down-regulation of 46 genes involved predominantly in branching morphogenesis, cell-adhesion, and future milk production in LH exposed mammary tissues. In 98 dpc placentomes, the distribution of trophoblast binucleate cells within feto-maternal junctions differed between fetal sex and maternal dietary exposure (p<0.05). In 98 dpc placentomes, SerpinB1 protein expression was observed to be high (96.5% of observed cells) in trophoblast binucleate cells (BNCs) bordering the maternal epithelial cell wall. While SerpinB1 expression was low (9.2% of observed cells) in BNCs localised centrally to the fetal cotyledons.

Results indicate that low maternal dietary protein increased fetal mammary expression of genes associated with the immune system, and decreased expression of genes associated with structural development. Histological results suggest that maternal diet did not affect total area, size, or number of fetal mammary ducts. Fetal mammary glands exposed to HPost diet had greater lumen size compared with LPost counterparts. This study provides a basis for future investigation of the fetal mammary gland. The long-term effects of maternal dietary intervention on fetal mammary development in beef cows are yet to be elucidated.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Rutland, Catrin S.
Mongan, Nigel
Keywords: fetal programming, maternal nutrition, epigenetic, dietary protein, bovine
Subjects: S Agriculture > SF Animal culture
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Veterinary Medicine and Science
Item ID: 63423
Depositing User: Lund, Emma
Date Deposited: 06 Jun 2023 08:32
Last Modified: 06 Jun 2023 08:33

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