Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) - Fundación Endocrinológica Infantil (FEI) - División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.
Instituto de Investigaciones Biomédicas (INBIOMED), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina.
Front Endocrinol (Lausanne). 2021 Mar 11;12:615678. doi: 10.3389/fendo.2021.615678. eCollection 2021.
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.
据推测，草甘膦（G）或其商业制剂 Roundup（R）可能导致男性生育能力受损。在这项研究中，我们研究了幼年雄性大鼠接受 G 或 R 治疗对血睾屏障功能和成年雄性精子生成的可能影响。幼崽被随机分配到以下组：对照组（C），接受水；G2 和 G50 组，分别接受 2 和 50mg/kg/天 G；和 R2 和 R50 组，分别接受 2 和 50mg/kg/天 R。从出生后第 14 天（PND）到 30 天进行治疗，这是完成功能性血睾屏障所必需的生命期。在 PND 31 进行评估。各组之间的体重和睾丸重量没有差异。睾丸组织学分析显示生精小管上皮排列紊乱，治疗动物的细胞粘附明显降低。检查生物素示踪剂对血睾屏障的通透性。在处理组中观察到通透性小管显著增加。为了评估可能解释血睾屏障通透性变化的机制，检查了睾丸内睾酮水平、雄激素受体表达、硫代巴比妥酸反应物质（TBARS）以及细胞间连接蛋白（claudin11、occludin、ZO-1、连接蛋白 43、46 和 50，它们是血睾屏障的组成部分）的表达。未检测到上述参数的变化。为了评估幼年时期接触 G 和 R 是否会对成年期产生影响，一组 R50 组的动物被允许生长至 PND 90。组织学分析表明，对照组和 R50 组的细胞连接正常，且具有完整的精子发生。此外，血睾屏障功能得到恢复，睾丸重量、每日精子生成以及附睾精子运动和形态似乎未因幼年期治疗而改变。总之，本文的结果表明，持续接触低剂量的 G 或 R 会改变幼年大鼠的血睾屏障通透性。然而，考虑到在幼年阶段接受治疗的成年动物与对照组动物相比，每日精子生成没有差异，因此认为血睾屏障受损是一种可逆现象。需要进一步的研究来确定接触低剂量 G 或 R 的人类幼年人群的生殖功能是否可能受损。
