Swerczek, T.W. and Dorton, A.R

Effects of nitrate on reproductive losses, congenital hypothyroidism and musculoskeletal abnormalities in foals

The Modern Equine Vet. 2019, Vol 9, pp. 17-18

Epidemiological and research findings provided evidence to support the hypothesis that excessive nitrate was associated with reproductive losses, congenital hypothyroidism, and musculoskeletal abnormalities in fetuses of mares and other animals. These fetal losses, with an unknown etiology, and associated with Mare Reproductive Loss Syndrome (MRLS), have plagued horse-farms in central Kentucky and elsewhere for decades.

Most fetal losses with an unknown etiology are related to environmental and climatic changes that affect pasture forages in the late spring and to a lesser extent in the early fall. During some foaling seasons, these reproductive losses may dramatically increase in late spring. An extraordinary increase in abortions was first recognized as a syndrome in the late spring of 1980 after pasture forages were stressed by droughts, frosts and freezes, and affected pasture forages and diets were found to be elevated in nitrate. Fetal losses occur in mares grazing spring pastures that are affected by climatic and environmental factors including droughts, cold-stress, nitrogenous fertilizers, and herbicides. These factors, among others, cause nitrate to accumulate in pasture forages.

Since 1980, similar fetal losses were recognized each spring. However, in the spring of 2001, there was a massive unprecedented increase in fetal losses when several thousand mares acutely aborted in central Kentucky and surrounding areas. Cold-­‐stress to pasture forages induced an acute pike in potassium and nitrate in damaged plants. Fetal losses, with an unknown etiology, that occurred after unseasonal climatic conditions in the late spring of 2001 were referred to as MRLS.

Increased reproductive losses in mares were most numerous in early developing fetuses, but they occurred at all stages of gestation starting 9 to 10 days after pasture forages were severely

stressed. Nitrate increases in pasture forage within 24 to 48 hours after cold-stress and will remain elevated until plants recover with new growth. The syndrome is more common after unseasonal late spring erratic weather patterns of droughts and cold-stress to pasture forages.

Affected fetuses that do not abort early in gestation when exposed to excessive nitrate, congenital abnormalities may occur in the umbilical cord and musculoskeletal system, primarily limb contractures. Severe and fatal congenital anomalies represent a small percentage of fetal losses. However, minor limb contractures, umbilical cord, and amnion lesions are common and often not fatal. Musculoskeletal abnormalities account for significant losses in newborn foals and mares may die during parturition due to dystocia and foaling complications related to limb contractures. Developmental anomalies, including contracted foal syndrome, with an unknown etiology, have been affecting foals in central Kentucky and elsewhere for decades.

On Thoroughbred horse farm where mares were aborting due to suspected nitrate toxicosis, and pathologic lesions consistent with MRLS also had a herd of pregnant Boer goats that were grazing similar pastures and they developed severe congenital goiter due to nitrate-induced hypothyroidism. The gross and microscopic lesions in the affected kid goats were identical to those seen in kid goats from pregnant does grazing pastures previously fertilized with ammonium nitrate. Seemingly, the pregnant Boer goat, and possibly other small ruminants, are ideal sentinel herbivores to detect nitrate toxicosis and congenital hypothyroidism in less sensitive animals, like affected foals that do not display any obvious clinical signs of goiter but do display remarkable lesions of congenital musculoskeletal abnormalities. Without the simultaneous observations and findings with pregnant Boer goats and pregnant mares consuming the same high nitrate pasture forages, it would have been challenging to have made the association between nitrate, reproductive losses, congenital hypothyroidism and musculoskeletal abnormalities in foals that are less sensitive to the same goitrogenic agent as kid goats.

Nitrate competes with iodide uptake by the thyroid and has been associated with alterations in iodine metabolism, thyroid activity, and thyroid gland morphology in several animal species. The obvious difference between species how the thyroid gland responds morphologically to the

apparent same goitrogenic agent is the reason why nitrate toxicosis was not previously associated with hypothyroidism and musculoskeletal abnormalities in foals.

Association between nitrate toxicosis and reproductive losses in mares and other herbivores is difficult to demonstrate that nitrate per se is responsible for fetal losses and congenital defects. However, since thyroid function and thyroid hormones are essential for early fetal development and maintenance of pregnancy explains why nitrate toxicosis is associated with hypothyroidism, reproductive losses and congenital defects. Nitrate levels at the time of abortions, or birth may be normal, but earlier in fetal development, nitrate may be elevated to the extent it affects normal early thyroid function, which is essential for fetal development and maintenance of pregnancy and prevention of reproductive losses, congenital defects, including musculoskeletal abnormalities.

It was found in 1980 and again in 2001, if pregnant mares were being supplemented with high-­‐protein feedstuffs and/or high-­‐protein alfalfa hay, they were more likely to abort after pastures spike in nitrate after frosts and freezes. Seemingly, the combination of nitrate from pasture forages and supplemental feedstuffs produced overwhelming nitrate toxicity.

Drastic unseasonal climatic changes that affect pasture forages cannot be prevented, but when they do occur, pasture grazing time should be limited until pasture forages return to normal which may take 2 to 3 weeks before damaged plants and the nitrate returns to normal levels. Reducing the protein in broodmare rations and increasing sodium in the form of salt, which seemingly neutralized high levels of nitrate, were beneficial in reducing fetal losses associated with high nitrate pasture forages.

If mares are bred early before the natural breeding season of April, May and June, they may be prone to fetal loss during the natural breeding season if they are exposed to toxic levels of nitrate from pasture forages and concurred high-­‐protein supplemental diets. Mares that are bred before the natural breeding need to be managed to prevent fetal loss during late spring when unseasonal climatic changes may occur. If early bred mares abort during the natural breeding season after endometrial cups form after 38 days of pregnancy to produce

equine chorionic gonadotropin, false pregnancy occurs and they will not return estrus until endometrial cups disappear which may take several months.

For more information see:

Swerczek, T.W., Dorton, A.R. Effects of nitrate and pathogenic nanoparticles on reproductive losses, congenital hypothyroidism and muscular abnormalities in mares and other livestock: new hypothesis. Animal and Veterinary Sciences. 2019:7(1):1-­‐11. Epub Feb. 13. http://www.animalvetsd.org/article/212/10.11648.j.avs.20190701.11