Soy contains phytoestrogens that can mimic estrogen in the body. The major phytoestrogens in soy are isoflavones like genistein and daidzein. Isoflavones are broken down and absorbed in the small intestine as aglycones via microbial enzymes. Once absorbed, the liver and microbes further metabolize isoflavones. Genistein in particular resembles the structure of estrogen and can bind to estrogen receptors, affecting reproductive tissues and hormone production in pigs. Studies show genistein increases growth of reproductive tissues and inhibits ovarian steroidogenesis and fertility in pigs. While soy is a cheap feed ingredient, the livestock industry should address phytoestrogens' potential negative impacts on pig

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Kietty Phuangpolchai
Non-Ruminant Nutrition
Phytoestrogen Effects in Absorption and Metabolism, and Its Impacts on
Reproductive Physiology in Pigs
Soy is commonly used as a protein source in animal feedstuffs and as an
ingredient in human food. Due to its abundance and low cost, the swine industry uses
soy as a main ingredient in the diet of pigs. However, soy contains phytoestrogens,
natural-occurring molecules found in plant products that have an ability to mimic
estrogen in the body [1]. Phytoestrogens play critical roles in absorption and metabolism
that are possibly associated with fertility in pigs.
Phytoestrogens have been classified in several different groups due to their
phenolic structure. Isoflavones, lignans, coumestants, and flavonoids are major groups
of phytoestrogens [2]. More classes of phytoestrogens are being discovered and each
class has its own unique characteristics of chemical structure, molecular properties, and
reaction to the surrounding environment [1- 3]. The major classes of phytoestrogens
that are commonly found in soy food are isoflavones and Flavonoid Quercetin [1,4-5].
Isoflavones have several different sub-compound structures. Some of these structures
are daidzein and genistein, biochanin A and formononetin [1, 3,6]. Each has a similar
property in mimicking endogenous Estradiol (E2) —one of the major classes in the
estrogen family that’s secreted from the ovaries. E2 is essential in normal female
reproductive function [1-2, 6]. Soy food is found to have all of these isoflavones
including Isoflavone genistein one of the most abundant that causes numerous effects

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in the body systems. This molecule affects absorption and metabolism, excretion, and
reproductive systems [1, 3-4, 6-20].
The isoflavone absorption mechanism has not been observed enough to report
conclusive information [3]. However, there have been some studies accomplished to
investigate the mechanism of dietary isoflavones in soy in luminal digestion. In regular
dietary soy, isoflavones exist in the form of glycoside—a sugar group attached to a non-
carbohydrate group [1,9]. This glycoside is later changed to genistein aglycones, which
occurs when a sugar group is removed from the compound via hydrolysis in the small
intestine [1,3,9]. It still remains unclear if glycosides need to be broken down to
aglycones prior to entering the membrane of the small intestine. However, it has been
shown that aglycone can travel across the membrane more easily than glycoside [3].
According to the Walsh et al. study, cannulae were inserted into the ileal part of the
small intestine. Aglycones were found in the cannula tube, implying that isoflavone
glycoside is mainly broken down in the upper part of small intestine in post weaned pigs
[9]. Glucosides are broken down by Beta-glucosidase enzymes secreted from
commensal organisms. Then the isoflavone is further digested in the large intestine and
absorbed as a form of aglycone [3,9,11].
Microbial enzymes are crucial as a part of isoflavone metabolism in pigs, unlike
in rodent species. When rats were fed a high content of phytoestrogen (Isoflavones-rich
food), their urine excretion showed presence of genistein and daidzein, but it was
absent of any bacterial activity [9]. Therefore, maintaining a proper environment in the
gastrointestinal tract is critical for pigs because isoflavone metabolism substantially
depends on the intestinal microorganisms. Despite the absorption of the genistein

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aglycones, the intestinal microbes are also a key factor in transforming the isoflavone
genistein structure into one that mimics the estrogen structure [10-11, 20].
Prior to isoflavone being absorbed in the enterocyte, the liver secretes the
cytochrome P450 isoenzyme that further breaks down the isoflavone genistein
compound [3, 20]. The microorganisms in the large intestine change the molecular
structure of genistein to dihydrogenistein, which eventually converts to para-
Ethylphenol, whereas daidzein forms to equol [1, 3,10, 21]. Currently, these isoflavone
metabolites’ pathways and their mechanism are not very well understood. Para-
Ethyphenol and equol are found in urinary excretion, and the quantities of these
metabolites that remain in urine greatly differ between species [11,21-22]. In a study
comparing phytoestrogen metabolism of different species, the isoflavone metabolites
were detected in urinary excretion. Female pigs were found to contain less equol than
rats or monkeys, but they have a similar isoflavone metabolism to female humans [21].
The structures of isoflavone genistein primarily contribute to regulating reproductive
tissues and hormonal mechanism in female pigs.
Several studies have been established finding that isoflavone genistein structure
closely resembles estradiol (E2), affecting estrogenic action in the reproductive system
[4,13-20]. Genistein can bind to the estrogen receptor and can act as sexual hormone
disrupter, either preventing the binding of estrogen to the receptor or alternatively
binding to the receptor itself [13,15, 20]. Different reproductive parameters are being
discussed to demonstrate isoflavone effects at a reproductive level.
Phytoestrogen genistein structure (4’, 5,7-trihydroxyisoflavone) is similar to that
of endogenous estradiol (17β-estradiol), which is composed of two hydroxyl groups.

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Despite the similarity in structures of these two compounds, genistein is found to have a
higher affinity for one of the estrogen receptors—ERβ, indicating potential effects on
Steroidogenic enzymes that may be associated with sexual hormone production. Due to
these characteristics, genistein is able to compete with estradiol for its binding site
(ERβ), causing different effects on reproductive system [1,5,18-20, 23-24].
In a recent study in genistein effects on estrogenic activity, genistein generated
tissues growth in ovariectomized gilts. Gilts that received high dosages of genistein at
levels of 400mg were found to have uterine and cervical tissue mass with an increase of
more than 250%, compared to those that did not receive any hormone treatment. These
results suggest that the reproductive cell tissues are highly receptive to the
administered phytoestrogen [14]. Further investigation of dietary soy and its isoflavone
concentration has not been evaluated, however the swine industry can view this
projection as a tool in understanding potential impact of isoflavone on reproductive
tissues of pigs.
The findings of phytoestrogen’s pathway in reproductive systems and its ability in
binding to estrogen receptors, show that the higher affinity that genistein displays for
ERβ over ER-alpha causes inhibitory effects on ovarian steroidogenesis [17-18]. The
Nynca et al. study examined effects of genistein on estrogen receptor ERβ in granulosa
cells of follicles and found that genistein enhances mRNA expression of ER-beta where
this is not seen in rodents [18]. The genistein binding to ER-beta causes estradiol
production increases. At the same time, progesterone hormone production was
suppressed as well as Protein Tyrosine Kinase activity. These inhibitions negatively
affect the process of ovulation, folliculogenesis, and corpus luteum formation, which are

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processes that help prepare endometrial cells for embryo implantation [18-19]. Each
reproductive phrase is crucial and can affect conception rate in pigs.
Although, there are currently no other cheap alternative feedstuffs that can
substitute soybean meal, the swine industry should not underestimate these possible
negative impacts that are correlated with long term feeding of dietary soy. Many studies
have raised concern with high consumption of soy food due to the post effects in
reproductive function. These negative effects should be address before the detrimental
consequences are seen in swine reproduction.

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