Comparative effects of finasteride and minoxidil on the male reproductive organs: A systematic review of in vitro and in vivo evidence.

Finasteride and minoxidil are medicaments commonly prescribed for treating benign prostatic hyperplasia (BPA), hypertension, and/or androgenetic alopecia (AGA). The mechanism of action of finasteride is based on the interference in androgenic pathways, which may lead to fertility-related disorders in men. Minoxidil, however, can act in multiple ways, and there is no consensus that its use can adversely affect male fertility. Since finasteride and minoxidil could be risk factors for male fertility, we aimed to compare their impact on the two reproductive organs testis and epididymis of adult murine models, besides testis/epididymis-related cells, and describe the mechanism of action involved. For such, we used the PRISMA guideline. We included 31 original studies from a structured search on PubMed/MEDLINE, Scopus, and Web of Science databases. For in vivo studies, the bias analysis and the quality of the studies were assessed as described by SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation). We concluded that finasteride and minoxidil act as hormone disruptors, causing oxidative stress and morphological changes mainly in the testis. Our results also revealed that finasteride treatment could be more harmful to male reproductive health because it was more associated with reproductive injuries, including damage to the epididymis, erectile dysfunction, decreased libido, and reduced semen volume. Thus, this study contributes to the global understanding of the mechanisms by which medicaments used for alopecia might lead to male reproductive disorders. We hope that our critical analysis expedites clinical research and reduces methodological bias. The registration number on the Prospero platform is CRD42022313347.

Toxicology of arsenate, arsenite, cadmium, lead, chromium, and nickel in testes of adult Swiss mice after chronic exposure by intraperitoneal route.

BACKGROUND: Some residues such as the heavy metals cadmium (Cd), lead (Pb), chromium (Cr VI), nickel (Ni), and arsenic (As), this last one in its oxidized forms + 5 (arsenate) and + 3 (arsenite), can cause injuries to human health, so they are currently considered environmental health emergencies. In the testis, heavy metals can cause morphological and functional damage due to constant exposure acting chronically in individuals. Thus, we aimed to determine the toxicological mechanism of As+5, As+3, Cd, Cr VI, and Ni that leads to testicular damage and establish for the first time an order of toxicity among these studied heavy metals. METHODS: Forty-two Swiss mice at reproductive age (140 days) were used, randomly distributed into seven experimental groups (n = 6). Exposure to heavy metals was weekly performed, by intraperitoneal route. Group 1 received 0.7 mL 0.9% saline (control), and the other groups received 1.5 mg/ kg of As+5, As+3, Cd, Pb, Cr VI, or Ni, for six weeks. RESULTS: These studied heavy metals did not accumulate in the testis tissue. However, exposure to Ni induced moderate pathologies in the seminiferous tubules, plus changes in the tunica propria, blood vessels, lymphatic space, and carbonyl protein levels. Cd exposure caused moderate tubular histopathologies and changes in the blood vessels and lymphatic space. Cr VI induced slight tubular histopathologies, changes in the lymphatic space, blood vessels, and SOD activity. Pb and As+3 exposure triggered moderate tubular pathologies and changes in the SOD activity and carbonyl protein levels, respectively. Finally, As+5 induced only slight tubular pathologies. CONCLUSION: The testicular histopathologies caused by the studied heavy metals are mainly triggered by changes in testicular oxidative balance. Based on our findings of histomorphological alterations, the toxicity order among the heavy metals is Ni>Cd>Cr(VI)>PbAs+3 >As+5. However, considering oxidative stress results, we propose the following testicular toxicity order for these heavy metals: Ni>As+3 > Cd>Cr(VI)>Pb>As+5. Ni exposure shows the most harmful among the heavy metals to the testis.

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

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.

Different Routes of Administration Lead to Different Oxidative Damage and Tissue Disorganization Levels on the Subacute Cadmium Toxicity in the Liver.

The toxic effects of cadmium (Cd) on hepatic parameters are widely described in the literature. Experimental models often make use of the intraperitoneal route (i.p.) because it is easier to apply, while in the oral route, Cd poisoning in humans is best represented by allowing the metal to pass through the digestive system and be absorbed into the bloodstream. Thus, this study investigated the Cd exposure impact on the liver, by comparing both i.p. and oral routes, both in single dose, in addition to the oral route in fractional doses. Swiss adult male mice received CdCl2 1.5 mg/kg i.p., 30 mg/kg oral single dose, and 4.28 mg/kg oral route in fractional doses for 7 consecutive days. Cd bioaccumulation was observed in all animals exposed to Cd. Hepatic concentrations of Ca and Fe increased only in the fractionated oral route. Liver activities of SOD and CAT increased only by oral single dose. GST decreased in all forms of oral administration, while MDA decreased only in i.p. route. Liver weight and HSI increased in the i.p. route, while organ volume increased in all forms of oral administration, and liver density increased in all animals exposed to Cd. In hepatic histomorphometry, the changes were more evident in oral administration, mainly in exposure to metal in a single dose. Thus, the subacute administration of Cd in different routes of administration leads to different changes in liver poisoning.