Chronic exposure during adulthood to a glyphosate based herbicide alters the expression of hormonal receptors in hypothalamic nuclei involved in the rat estrous cycle regulation

STOKER C; SCHUMACHER R; VARAYOUD J; CANESINI G; ROSSETTI MF; DURANDO M; LAZZARINO GP; GASTIAZORO MP; RAMOS JG

Buenos Aires

Congreso; XX Jornadas anuales de la Sociedad Argentina de Biologría (SAB) XVII Jornadas de la Sociedad Uruguaya de Biociencias (SUB).; 2018

Glyphosate-based herbicides (GBHs) are extensively used to control weeds on both cropland and non-cropland areas. In Argentina, glyphosate is the most commonly used herbicide, with around 200?260 million liters applied every year. It has been reported that GBHs may act as an endocrine disruptor. However, the possible consequences of this pesticide exposure on fertility and specifically on hypothalamic function remains poorly understood. In the normal cycling rat, an increase in luteinizing hormone (LH) occurs, triggered by the neurosecretion of the LH-releasing hormone (LHRH), also known as gonadotropin-releasing hormone (GnRH). In rats, the majority of LHRH-secreting neurons are located in the preoptic area of the hypothalamus. Activation of steroid receptors in specific hypothalamic regions like the anteroventral periventricular nucleus (AvPv) and the arcuate nucleus (Arc) is also necessary to achieve a normal LH surge. The aim of this study was to describe the effects of chronic exposure during adult life at a dose of GBH close to the reference dose, on the estrous cycle of the rat and on the expression of key proteins of the hypothalamic nuclei involved in its regulation. Adult rats were exposed for 3 months in the pellet chow to 2 mg/kg/day of GBH (GBH group- GG) or control diet (pellet chow with saline solution ? control group- CG). The estrous cycle was monitored by vaginal cytology for two weeks and finally the animals were sacrificed approximately at day 240 of age in diestrous stage. The brains were dissected, fixed and included in paraffin, and coronal sections of 5µm were obtained by microtomy. The estrogen receptor alpha (ERα) and progesterone receptor (PR) were assessed by inmunohistochemistry (IHC) in hypothalamic AvPv, Arc and medial preoptic (Mpo) nuclei. The estrous cycle of GG animals was affected since they showed a low percentage of time in the proestrous-estrous stages when they were compared to CG. ERα expression was significantly lower in GG respect to CG, in the three nuclei evaluated. Moreover PR expression was lower in AvPv nucleus of GG rats and significantly higher in Mpo and Arc nuclei in GG respect to CG. These results show that a dose of GBH considered safe, administered chronically through diet in adult life, alters the rat´s cyclicity and modifies the expression of key brain proteins involved in its regulation. Furthermore, these changes may provide new evidence on the possible effects produced by glyphosate at hypothalamic level that could affect fertility.