Abstract
It has been postulated that glyphosate (G) or its commercial formulation Roundup (R) might lead to male fertility impairment. In this study, we investigated the possible effects of G or R treatment of juvenile male rats on blood-testis barrier function and on adult male sperm production. Pups were randomly assigned to the following groups: control group (C), receiving water; G2 and G50 groups, receiving 2 and 50 mg/kg/day G respectively; and R2 and R50 groups receiving 2 and 50 mg/kg/day R respectively. Treatments were performed orally from postnatal day (PND) 14 to 30, period of life that is essential to complete a functional blood-testis barrier. Evaluation was done on PND 31. No differences in body and testis weight were observed between groups. Testis histological analysis showed disorganized seminiferous epithelium, with apparent low cellular adhesion in treated animals. Blood-testis barrier permeability to a biotin tracer was examined. A significant increase in permeable tubules was observed in treated groups. To evaluate possible mechanisms that could explain the effects on blood-testis barrier permeability, intratesticular testosterone levels, androgen receptor expression, thiobarbituric acid reactive substances (TBARS) and the expression of intercellular junction proteins (claudin11, occludin, ZO-1, connexin43, 46, and 50 which are components of the blood-testis barrier) were examined. No modifications in the above-mentioned parameters were detected. To evaluate whether juvenile exposure to G and R could have consequences during adulthood, a set of animals of the R50 group was allowed to grow up until PND 90. Histological analysis showed that control and R50 groups had normal cellular associations and complete spermatogenesis. Also, blood-testis barrier function was recovered and testicular weight, daily sperm production, and epididymal sperm motility and morphology did not seem to be modified by juvenile treatment. In conclusion, the results presented herein show that continuous exposure to low doses of G or R alters blood-testis barrier permeability in juvenile rats. However, considering that adult animals treated during the juvenile stage showed no differences in daily sperm production compared with control animals, it is feasible to think that blood-testis barrier impairment is a reversible phenomenon. More studies are needed to determine possible damage in the reproductive function of human juvenile populations exposed to low doses of G or R.
Highlights
Glyphosate (G)-based herbicides are important tools used worldwide in agriculture, forestry, and weed control [1]
All the procedures used in this study were approved by the Comité Institucional de Cuidado y Uso de Animales de Laboratorio (CICUAL) from the Hospital de Niños Ricardo Gutiérrez (Res #2018-002) and performed in accordance with the principles and procedures outlined in the Guide for the Care and Use of Laboratory Animals issued by the National Institute of Health of USA. 3-month-old pregnant Sprague Dawley rats (250–300 g) were purchased from the bioterium of the Facultad de Ciencias Veterinarias, Universidad de Buenos Aires (FCVUBA)
Between 1973 and 2011 among men unselected by fertility from North America, Europe, Australia, and New Zealand [31] arose considerable scientific and public concern regarding the adverse effects of various environmental contaminants on male reproduction
Summary
Glyphosate (G)-based herbicides are important tools used worldwide in agriculture, forestry, and weed control [1]. G prevents plant development by inhibiting the enzyme enolpyruvylshikimate phosphate synthase (EPSPS) and interfering with the synthesis of essential aromatic amino acids [5]. As this enzyme is not expressed by any member of the animal kingdom, the actions of G were supposed to be present exclusively in plants [6, 7]. Most of them were performed using doses far above the maximum dietary and environmental exposure levels reported in humans For this reason, whether G is harmful to male reproductive health when exposure occurs at low doses and at early life stage is still under debate
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