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Folic acid and pigs born alive

The importance of folic acid sufficiency to sound reproductive performance in sows is well documented. Researchers such as Matte et al. (1992), Lindemann (1993) and Lindemann and Kornegay (1989) have reported up to 10 percent more pigs born alive, as well as improved pig health through weaning, when sows received dietary folic acid supplementation throughout gestation (Figure 1). There's also general agreement that the increase in live births is due to reduced embryonic mortality in early gestation.

Work by Matte et al. (1996) suggests that the improved performance is due to influences on both embryo development and uterine secretions. In this study, multiparous sows received either 0 or 15 ppm of supplemental folic acid beginning two weeks before mating and continuing through 15 days after mating, when the study ended. These first two weeks of gestation are critical for embryonic development and are also a period when folate requirements surge.

Indeed, by day 12 of gestation, the folate levels of unsupplemented sows declined significantly from the levels at mating. Serum folate decreased by 20 percent, and bound folate, as measured by total and saturated binding capacity, declined by 12 percent and 24 percent, respectively (Figures 2 and 3). The researchers noted that these decreases probably reflected folate requirements that were met at the expense of reserves.

Dietary supplementation of folic acid at 15 ppm apparently satisfied the increased folate demand. The decline in the serum folate levels was limited to 5 percent, total folate binding capacity remained constant, and saturated folate binding capacity actually increased by about 45 percent (Figures 2 and 3).

That the developing embryo would have its own folate requirement for normal growth and differentiation is wholly consistent with the vitamin's key role in cell formation and function. Folic acid is essential for the transfer of single carbon units in the synthesis of purine and pyrimidine bases and the metabolism of methionine, choline and thymine. Purine bases and thymine (a pyrimidine base) are constituents of nucleic acids, and folic acid appears necessary for mitosis.

Work in rats has documented an interaction between the folate status and protein content of embryos. Miller et al. (1989) found reduced protein content in 9.5-day-old embryos when these were cultured in serum from folic acid-deficient rats. The researchers could restore the embryos' protein content to normal levels by supplementing the serum with folic acid.

In the current study (Matte et al., 1996), the researchers reported that on day 12 of gestation, protein content was 10 percent greater (P < 0.07) in embryos from supplemented sows. This was one of two indications that the embryos of supplemented sows were more developed at the same stage of gestation than the embryos of unsupplemented sows.

The other indication was lower estrogen production. While early pregnancy is a period of intense estrogen secretion by the embryo and the endometrium, production decreases as the embryo develops. The researchers reported that estrogen levels at day 12 of gestation were about 30 percent lower (P < 0.004) in sows fed the supplemental folic acid.

These results concur with those from similar studies. For example, Tremblay et al. (1989) reported a 5 percent increase in protein content of embryos on day 30 of gestation when the sows received 5 ppm of dietary folic acid compared to unsupplemented controls. Harper et al. (1996) also found improvements in several important criteria associated with placental and fetal growth in supplemented sows. Among these were greater wet and dry weight (P < 0.01) and crown-rump length (P < 0.05) in the fetuses of supplemented sows. Because of the heavier weights, there were also increases in total protein and RNA quantities (P < 0.05) in the fetuses of supplemented sows.

Matte et al. (1996) also detected differences in other factors affecting embryonic development and survivability. For example, total recoverable prostaglandin (PG) E2 was three times greater (P < 0.04) in supplemented than unsupplemented sows by day 12 of gestation. Bazer et al. (1991) suggested that uterine prostaglandins may be involved in the formation of the placenta because they affect water and electrolyte transport, vasodilation and vascular permeability. Placental growth during early pregnancy is particularly important because it is minimal after day 60 but the fetus continues to grow. Harper et al. (1996) did detect trends for increased placental length (P < 0.10) and placental weight (P < 0.11) in supplemented sows.

In addition, these prostaglandins may also reduce the maternal immune response during and after the embryo attachment to the uterine wall. Yu et al. (1994) reported that PGE2 inhibits cytotoxic activity against the trophoblastic cells--the outermost layer of embryonic cells that attach the fertilized ovum to the uterine wall and serve as a nutritive pathway.

Matte et al. (1996) noted that it remains to be determined whether the effect of folic acid supplementation is exerted initially on the embryos and then favorably alters the uterine secretions or whether these effects occur simultaneously. The researchers also suggest that further work on the optimum dietary levels of folic acid for sows is needed. The current DSM Nutritional Products recommended fortification level is 3 ppm (2.7 g per ton of complete feed); however, Matte et al. (1996) fed 15 ppm because of past work in which litter size and pig health were optimized at that level.

References:

Bazer, F.W., et al., 1991. Composition of uterine flushings from Large White and prolific Chinese Meishan gilts. Reprod. Fert. Develop. 3:51.
Harper, A.F., et al., 1996. Fetal survival and conceptus development after 42 days of gestation in gilts and sows in response to folic acid supplementation. Can. J Anim. Sci. 76:157.
Lindemann, M.D. 1993. Supplemental folic acid: a requirement for optimizing swine reproduction. J. Anim. Sci. 71:239.
Lindemann, M.D., and E.T. Kornegay. 1989. Folic acid supplementation to diets of gestating-lactating swine over multiple parities. J. Anim. Sci. 67:459.
Matte, J.J., et al., 1992. The role of folic acid in the nutrition of gestating and lactating primiparous sows. Livest. Prod. Sci. 32:131.
Matte, J.J., et al., 1996. Dietary folic acid, uterine function and early embryonic development in sows. Can. J. Anim. Sci. 76:427.
Miller, P.N., et al., 1989. Growth of 9.5-day rat embryos in folic-acid-deficient serum. Teratology. 39:375.
Tremblay, G.F., et al., 1989. Survival rate and development of fetuses during the first 30 days of gestation after folic acid addition to a swine diet. J. Anim. Sci. 67:724.
Yu, Z., et al., 1994. Lysis of porcine trophoblast cells by endometrial natural killer-like effector cells in vitro does not require interleukin-2. Biol. Reprod. 51:1279.