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.
Highlights
Phytoestrogens, especially soy isoflavones, are natural nonsteroidal compounds of plant origin found mainly in the Fabaceae family [1]. e chemical structure and function of isoflavones are similar to estradiol and, their therapeutic effect has been studied in a variety of estrogendependent diseases such as menopause, cardiovascular disease, and osteoporosis [1]
Pathological changes were found in all studies selected in this review. e changes in biological processes found in the testicular structure after exposure to isoflavones have been described in detail in Figure 4, showing greater evidence of changes in molecular functions and cellular components
Biological Processes. e exposure of male rats to isoflavones increased the levels of estrogen receptor α (ESR1), mitogen-activated protein kinase 3/1 (MAPK 3/1), protein kinase B (AKT1), pAKTSer473, and [3H] ymidine in Leydig cells (LC) (n 1; 4.54%). e same study observed an increase in Cyclin D3, nuclear cell antigen proliferation (PCNA) proteins (n 2, 9.09%), and decreased expression of translocator protein/β (TSPO/β) and steroidogenic acute regulatory protein/β (StAR/β) in vitro (Figure 3)
Summary
Phytoestrogens, especially soy isoflavones, are natural nonsteroidal compounds of plant origin found mainly in the Fabaceae family [1]. e chemical structure and function of isoflavones are similar to estradiol and, their therapeutic effect has been studied in a variety of estrogendependent diseases such as menopause, cardiovascular disease, and osteoporosis [1]. E chemical structure and function of isoflavones are similar to estradiol and, their therapeutic effect has been studied in a variety of estrogendependent diseases such as menopause, cardiovascular disease, and osteoporosis [1]. Phytoestrogens, especially soy isoflavones, are natural nonsteroidal compounds of plant origin found mainly in the Fabaceae family [1]. Isoflavones such as genistein, daidzein, formononetin, biochanin A, and equol can be found in different types of food such as leguminous (especially soybean), whole grains, and some seeds used in the human diet [2].
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