Folic acid and vitamin B12 in reproducing sows: New concepts

In pig nutrition, the present gaps in the information on B-complex vitamins have important implications for empiricism and disparities in dietary recommendations. This is particularly true for folic acid (B9) and vitamin B12. Recent studies suggest that the beneficial effects of B9 on sow prolificacy may be due to enhanced embryo development and survival. Embryo synthesis of estrogens and uterine secretions of prostanoids and cytokines during attachment appear to be key factors in vitamin B9 regulation of embryo development. Nevertheless, embryo and uterine responses to B9 are often more pronounced in multiparous sows than in gilts. This parity effect on B9 responses can be attributed to the metabolic interaction with another vitamin, specifically B12. The two vitamins are essential for modulating the transfer of one-carbon groups for protein and DNA synthesis, methylation and gene expression. The metabolic pathway involved is the remethylation of methionine from an intermediary metabolite, homocysteine. A deficiency in B9 or B12 mayinduce a local or systemic accumulation of homocysteine, a powerful pro-oxidant known to impair embryo development. It appears that B12 status, which is about two times lower in gilts than in multiparous sows, could be a limiting factor for the action of vitamin B9 on uterus and embryo metabolism during the first pregnancy. Vitamin B12 status is particularly critical since, in early gestation, the sow uterus drains off a massive amount of B12, representing two to three times the B12 plasma pool. Dietary B12, at levels 10 times higher than recommended, have been found to maximize B12 status and minimize homocysteine accumulation in first parity sows. It appears that an optimum B9:B12 ratio, which has yet to be estimated, would enable vitamin B9 to have full beneficial effects on sow prolificacy. In the future, it is likely that there will be an even greater need for updated information on the requirements for B-complex vitamins given the “dietary fine tuning” that is necessary for the highly producing pigs that have been selected in recent decades. Key words: Folic acid, vitamin B12, reproduction, pig

Reproductive performance and uterine prostaglandin secretion in gilts conditioned with dead semen and receiving dietary supplements of folic acid

The effects of dietary supplements of folic acid at 0 (F−) or 15 ppm (F+) and of conditioning the uterus (C+) or not (C−) with an intrauterine infusion of dead semen on embryonic survival and prostaglandin E2 (PGE2) concentrations in the allantoic fluid on day 30 of gestation were studied. Sixty-four F1 crossbred gilts (Yorkshire × Landrace) were used in a 2 × 2 factorial design. The initiation of folate supplementation and the intrauterine infusion of dead semen were done at the estrus preceding the fertile mating. Folate status in serum was lower in F+ gilts than in F− gilts during the estrus cycle (folic acid × period interaction, P ≤ 0.007). Conditioning increased ovulation rate in F− gilts while it tended to decrease it in F+ gilts (interaction folic acid × conditioning, P ≤ 0.03). A similar interaction (P ≤ 0.02) was observed on the number of presumably live embryos at 30 d of gestation. Mean PGE2 concentration in the allantoic fluid was not affected by treatments (P ≥ 0.44), but the frequency of sows having elevated allantoic PGE2 (> 4 ng mL−1) tended to be higher (P ≤ 0.06) in F+ sows. Overall values of PGE2 were correlated with total litter weight (R2 = 0.54). In conclusion, there was no synergism between folic acid supplements and conditioning of the uterus with dead semen on the reproductive performance or on the secretion of allantoic PGE2 at 30 d of gestation. The secretion of allantoic PGE2 appears as an important factor involved in the control of litter size and weight. Key words: Folic acid, artificial insemination, semen, gilts, conditioning, embryo mortality

Pre- and post-mating dietary supplements of folic acid and uterine secretory activity in gilts

The present study was carried out to determine the effects of pre- and (or) post-mating dietary supplements of folic acid on uterine secretions and secretory activity on day 12 of gestation. Crossbred gilts were assigned randomly to three treatments: SS) a dietary supplement of 15 mg of folic acid kg−1 of diet from the estrus before mating (approximately day –21) until day 12 of gestation (n = 9), 0S) the same folic acid supplement from mating (day 0) to day 12 of gestation (n = 10), and 00) no supplement of folic acid (n = 10). At slaughter (day 12 of gestation), one uterine horn was flushed with 20 mL of PBS to collect embryos and uterine flushings, while samples of uterine tissue were collected from the other horn. Supplementary folic acid (0S and SS) increased total folates in uterine flushings (P ≤ 0.05) as well as concentrations of folates in the endometrium (P ≤ 0.0004) and in the whole uterine tissue (endometrium + myometrium: P ≤ 0.0001). Total amounts of prostaglandin (PG)E2 and PGF2α in uterine flushings were not affected (P ≥ 0.8) by any treatment but estradiol-17β was numerically 40% lower (P ≥ 0.12) in uterine flushings of 0S and SS sows. Samples of endometrium (15–17 mg) were cultured for 2 to 7 h. Concentrations of PGE2 and PGF2α in the culture medium increased with the duration of incubation (P ≤ 0.0001) but there was no treatment effect (P ≥ 0.4). The inconsistency between the folic acid response seen in the present study and in previous results using multiparous sows suggests that the impact of this vitamin on sow reproduction might be linked to the parity (and/or prolificacy) of the animal. Key words: Folic acid, uterine tissue, secretion, prostaglandins, gilts

Serum clearance and urinary excretion of folic acid in milk-fed and weaned calves

Thirty male calves were assigned to treatments in a 2 × 3 factorial experiment in which the diet (exclusively milk replacers or dry feed) and the duration of the period of folic acid supplementation (no, short-term, i.e., 7 d before each period of evaluation of the folate status, or long-term supplementation, i.e., throughout the experiment) were the two main factors. During their first 4 mo of life, the folate status of calves was evaluated monthly. In milk-fed calves, erythrocyte concentration of folates increased with the duration of the supplementation (P = 0.008) but it decreased with age (P = 0.01). In weaned calves, it was similar for calves receiving no or a short-term supplementation but it was higher for those receiving the long-term supplementation and the decrease with age was more marked with this last treatment (supplementation × age, P = 0.01). Serum clearance of an i.v. bolus of folic acid was similar for milk-fed and weaned calves (P = 0.2), it was more rapid with age (P = 0.02), but it slowed down with the duration of the supplementation (P = 0.05). The percentage of the dose of folic acid injected i.m. recovered in urine was higher in milk-fed than in weaned calves (P = 0.0001) and it decreased with age (P = 0.0001). The present results suggest that the tissue demand for folic acid is high in preruminant and ruminant calves and it increases during the first 4 mo of life. Key words: Folic acid, serum clearance, urinary excretion, milk-fed calf, weaned calf

Dietary folic acid, uterine function and early embryonic development in sows

The present study was designed to determine the role of folic acid on uterine environment and embryonic development during early gestation in the pig. Thirty-two, third parity, crossbred sows received a diet supplemented with 0 or 15 mg kg−1 of folic acid. The treatments started 2 wk before expected estrus and lasted until slaughter on either day 12 or 15 after mating. One uterine horn was used to collect conceptuses and uterine "flushings" for hormonal and metabolite determinations; conceptuses from the other horn were enzymatically dispersed and placed in cell culture with and without dehydroepiandrosterone (DHEA). The decrease in serum folates was attenuated (P ≤ 0.06) and the total and saturated folate binding capacities in early gestation were increased (P < 0.01) in sows receiving additional dietary folic acid. The volume of uterine flushings recovered was greater (P ≤ 0.02) on day 15 than on day 12, as was its content of protein (P ≤ 0.06). In sows receiving the dietary supplement of folic acid, total uterine prostaglandin (PG)E2 was three times higher on day 12 and two times higher on day 15 (P < 0.04) than for sows fed the experimental diet without supplement; although numerically substantial (60% higher), the effect was not significant for PGF2α (P ≥ 0.16). Conceptus homogenates contained more folic acid (P ≤ 0.02) and DNA (P ≤ 0.0001) on day 15 than on day 12. Their total protein content, in sows slaughtered on day 12 of gestation, tended (P ≤ 0.07) to be higher in supplemented than in unsupplemented animals. The synthesis of estradiol-17β by the conceptus cells, used as an index of embryonic maturity, tended (P ≤ 0.07) to be lower for treated than untreated sows, especially in conceptus cell culture without DHEA. Therefore, the improvement in embryonic survival attributed to dietary supplements of folic acid might be linked to changes on the secretion of uterine prostaglandins and possibly on embryonic development. Key words: Folic acid, uterus, embryo, sow

Fetal survival and conceptus development after 42 days of gestation in gilts and sows in response to folic acid supplementation

The effects of feeding 2 ppm supplemental folic acid (FA) on fetal survival and development were assessed in sows (n = 32). Number of live fetuses and fetal survival at day 45 ± 3 of gestation was not influenced by FA. Fetal pig weight, length, protein and RNA content were increased (P < 0.05) with FA treatment, suggesting enhanced development of embryo/fetal tissues with maternal FA supplementation. Key words: Folic acid, gilt, sow, fetal pigs

Effects of intramuscular injections of folic acid on folates status and growth performance of weanling pigs

In the first of two trials, 24 piglets (2 wk old) were used to measure the dose–response curve of serum folates after intramuscular injections of folic acid (0, 10, 20 or 30 mg). Administration of 10 mg of folic acid was sufficient (P < 0.01) to prevent the decrease of serum folates observed 1 wk after weaning. In the second trial, 72 piglets (2 wk old) were used to study the effect of repeated intramuscular injections of folic acid (0 or 2.5 mg kg−1 of body weight) on hematological status, liver development, and concentrations of serum and hepatic folates, as well as on growth performance up to 10 wk of age. Serum and liver folates were increased (P < 0.01) by repeated injections of folic acid. However, no treatment effects (P > 0.10) were observed on total content of DNA, RNA and protein in the liver. Hemoglobin, hematocrit, total body weight gain, gain: feed ratio and total feed intake were also not influenced (P > 0.10) by the injections of folic acid. Therefore, although a decrease in serum folates is observed during the weaning period, it does not seem to have detrimental effects on the growth performance of weanling piglets. Key words: Folic acid, folates, growth performance, piglets, weaning