Sex-Specific Muscular Maturation Responses Following Prenatal Exposure to Methylation-Related Micronutrients in Pigs

Abstract

Supplementation of micronutrients involved in DNA methylation, particularly during pregnancy, is recommended because of its impacts on human health, but further evidence is needed regarding the effects of over-supplementation and differences between sexes. Here, a porcine model was used to assess effects of maternal supplementation with one-carbon-cycle compounds during prenatal and postnatal stages on offspring muscle development. Sows received either a standard diet (CON) or a standard diet supplemented with folate, B6, B12, methionine, choline, and zinc (MET) throughout gestation. Myogenesis-, growth-, and nutrient utilization-related transcript expression was assessed using quantitative PCR. Organismal phenotype and gene expression effects differed significantly between males and females. Male MET-offspring showed increased fetal weight during late pregnancy but decreased live weight postnatally, with compensatory transcriptional responses comprising myogenic key drivers (Pax7, MyoD1, myogenin). In contrast, female weights were unaffected by diet, and mRNA abundances corresponded to a phenotype of cellular reorganization via FABP3, FABP4, SPP1 and Insulin-like Growth Factor-signaling. These findings in an animal model suggest that supplementation during pregnancy with methylation-related micronutrients can promote sex-specific myogenic maturation processes related to organismal growth and muscle metabolism. The usage of maternal dietary supplements should be more carefully considered regarding its ability to promote fetal and postnatal health.

Maternal Methyl-Donor Micronutrient Supplementation During Pregnancy Promotes Skeletal Muscle Differentiation and Maturity in Newborn and Weaning Pigs

“…The MET-supplemented gestation diet contained 4,700 mg kg −1 methionine (CJ BIO, Malaysia, purity ≥99%), 16.3 mg kg −1 folic acid (Sigma-Aldrich, St. Louis, MO, United States, purity ≥97%), 2,230 mg kg −1 choline (NB GROUP, Shandong, China, purity = 60%), 0.15 mg kg −1 vitamin B12 (Sigma-Aldrich, purity ≥98%), and 1,180 mg kg −1 of vitamin B6 (Jiangxi Tianxin Pharmaceutical, Jiangxi, China, purity ≥98%). Previous reports were used as references to determine the treatment dosages of folic acid (22), vitamin B12 (9, 23), methionine, choline, and vitamin B6 (19,24). During lactation, sows received a standard lactation diet ( Table 2).…”

Maternal diet induces persistent DNA methylation changes in the muscle of beef calves

“…Interestingly, previous studies in beef and sheep have also shown that maternal nutrition during gestation can alter the expression of genes related to muscle contraction in the offspring 27 , 28 . Similarly, previous studies in pigs have shown that supplementation during pregnancy with methylation-related micronutrients, such as folate, B6, B12, methionine, choline, and zinc, can promote sex-specific myogenic maturation processes related to growth and muscle metabolism 29 . Maternal methionine supplementation also persistently impacted the cytoskeleton of the muscle cells, and in particular the microtubules.…”

Folate treatment of pregnant rat dams abolishes metabolic effects in female offspring induced by a paternal pre-conception unhealthy diet

“…Folate treatment during pregnancy prevents adverse developmental programming [19,20,25]. A recent study showed that the effects on the offspring of folate during pregnancy are sexspecific [34]. We demonstrated that folate treatment of pregnant dams prevents adverse metabolic effects of paternal programming.…”