Methionine Supply During Late-Gestation Triggers Offspring Sex-Specific Divergent Changes in Metabolic and Epigenetic Signatures in Bovine Placenta

J Nutr. 2019 Jan 1;149(1):6-17. doi: 10.1093/jn/nxy240.

Abstract

Background: Nonruminant male and female offspring respond differently to gestational nutrition, with placenta contributing to the underlying mechanisms. However, similar data are lacking in large ruminants.

Objectives: The aim of this study was to investigate the impact of methionine supply during late-gestation on metabolism and DNA methylation in placenta from cows carrying male or female calves.

Methods: During the last 28 d of pregnancy, cows were individually fed a control diet (CON) or the control diet plus rumen-protected d,l-methionine (MET; 0.9 g/kg dry matter intake). Placentomes collected at term were classified according to cow dietary treatment and offspring sex as follows: Male CON (n = 7), Male MET (n = 7), Female CON (n = 8), and Female MET (n = 8). Calf growth was measured until 9 wk of age. Targeted metabolomics, RT-PCR, global DNA methylation, and activity of selected enzymes in one-carbon metabolism and transsulfuration pathways were performed. Statistics were conducted via ANOVA using MIXED models.

Results: At birth, Male MET calves were heavier than Male CON calves (7.6%, P = 0.02), but body mass was similar at 9 wk of age. In contrast, compared with Female CON, Female MET calves had greater body mass at 9 wk of age (6.3%, P = 0.03). Compared with Male CON, placenta from Male MET calves had greater concentrations of tricarboxylic acid (TCA) cycle and transsulfuration intermediates (23-100%, P < 0.05), along with greater 5-methyltetrahydrofolatehomocysteine methyltransferase activity (67%, P = 0.03). Compared with Female CON, placenta from Female MET calves had greater concentrations of one-carbon metabolism intermediates (13-52%, P < 0.05). DNA methyltransferase 3A (DNMT3A) was upregulated (43%, P < 0.01) in placenta from Female MET compared with Female CON calves. Global DNA methylation was lower in placenta from Female MET compared with Female CON calves (45%, P = 0.06).

Conclusions: Methionine supply affects placental metabolism, DNA methylation, and body mass of the calf in a sex-specific manner, underscoring its importance as dietary methyl-donor for pregnant cows.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animal Nutritional Physiological Phenomena
  • Animals
  • Biomarkers
  • Cattle
  • DNA Methyltransferase 3A
  • Diet / veterinary
  • Dietary Supplements
  • Epigenesis, Genetic / drug effects*
  • Female
  • Fetus
  • Male
  • Methionine / pharmacology*
  • Placenta / metabolism*
  • Pregnancy
  • Pregnancy, Animal* / drug effects
  • Prenatal Nutritional Physiological Phenomena

Substances

  • Biomarkers
  • DNMT3A protein, human
  • Methionine
  • DNA Methyltransferase 3A