Relevance of the Isoflavone Absorption and Testicular Function: A Systematic Review of Preclinical Evidence

Abstract

Isoflavone is a phytoestrogen found in different types of food that can act as endocrine disrupters leading to testicular dysfunction. Currently, fragmented data on the action of this compound in the testicles make it difficult to assess its effects to define a safe dose. Thus, we systematically reviewed the preclinical evidence of the impact of isoflavone on testicular function. We also determined which form (aglycones or glycosylated) was the most used, which allowed us to understand the main biological processes involved in testicular function after isoflavone exposure. This systematic review was carried out according to the PRISMA guidelines using a structured search on the biomedical databases MEDLINE (PubMed), Scopus, and Web of Science, recovering and analyzing 22 original studies. The bias analysis and the quality of the studies were assessed by the criteria described in the risk of bias tool developed by SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation). The aglycones and glycosylated isoflavones proved to be harmful to the reproductive health, and the glycosylates at doses of 50, 100, 146, 200, 300, 500, and 600 mg/kg, in addition to 190 and 1000 mg/L, appear to be even more harmful. The main testicular pathologies resulting from the use of isoflavones are associated with Leydig cells resulting from changes in molecular functions and cellular components. The most used isoflavone to evaluate testicular changes was the genistein/daidzein conjugate. The consumption of high doses of isoflavones promotes changes in the functioning of Leydig cells, inducing testicular changes and leading to infertility in murine models.

Figure 1

Flow diagram of the systematic review literature search results based on PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) (http://www.prisma-statement.org/).

Figure 2

Main forms of isoflavones administration and their physiological changes in murine models: (a) percentage of isoflavones used; (b) chemical form of the aglycone isoflavone; (c) chemical form of the glycosylated isoflavone; (d) percentage of the isoflavones administered, isolated and conjugated; (e, f) main biological processes that led to physiological changes.

Figure 3

General results of included studies showing the action of isoflavones on testicular function in murine models. GCs: germ cells; ↑: increased; ↓: decreased.

Figure 4

Main biological processes that induce testicular changes after exposure to isoflavones in murine models. Molecular functions involving the nucleus of the Leydig cells and cytoplasmic components (a, b). Molecular functions involving changes in the hypothalamic-pituitary gonadal axis (HPG) (c). I: intertubular; ST: seminiferous tubule.

Figure 5

Representation of different doses of isoflavones and their implications for testicular changes.

Figure 6

Results of the risk of bias and methodological quality indicators at an individual level (a) and all included studies in this systematic review (b) that evaluated the effect of isoflavone in testicular structure. The items in the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias assessment were scored with “yes” indicating low risk of bias, “no” indicating high risk of bias, or “unclear” indicating that the item was not reported, resulting in an unknown risk of bias.