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

CANESINI, GUILLERMINA; STOKER, CORA; LAZZARINO, GISELA PAOLA; ROSSETTI, MARÍA FLORENCIA; SCHUMACHER ROCÍO; GASTIAZORO MP; DURANDO, MILENA L.; VARAYOUD, JORGELINA; RAMOS, JORGE GUILLERMO

Buenos Aires

Jornada; XX Jornadas Anuales de la Sociedad Argentina de Biología (SAB).; 2018

SAB

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 GBHsmay act as an endocrine disruptor. However, the possible consequences of this pesticide exposure on fertility and specifically onhypothalamic function remains poorly understood. In the normal cycling rat, an increase in luteinizing hormone (LH) occurs, triggeredby the neurosecretion of the LH-releasing hormone (LHRH), also known as gonadotropin-releasing hormone (GnRH). In rats, themajority of LHRH-secreting neurons are located in the preoptic area of the hypothalamus. Activation of steroid receptors in specifichypothalamic regions like the anteroventral periventricular nucleus (AvPv) and the arcuate nucleus (Arc) is also necessary to achieve anormal 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 thereference 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 withsaline solution ? control group- CG). The estrous cycle was monitored by vaginal cytology for two weeks and finally the animals weresacrificed approximately at day 240 of age in diestrous stage. The brains were dissected, fixed and included in paraffin, and coronalsections of 5µm were obtained by microtomy. The estrogen receptor alpha (ERα) and progesterone receptor (PR) were assessed byinmunohistochemistry (IHC) in hypothalamic AvPv, Arc and medial preoptic (Mpo) nuclei. The estrous cycle of GG animals wasaffected since they showed a low percentage of time in the proestrous-estrous stages when they were compared to CG. ERα expressionwas significantly lower in GG respect to CG, in the three nuclei evaluated. Moreover PR expression was lower in AvPv nucleus of GGrats 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 inits regulation. Furthermore, these changes may provide new evidence on the possible effects produced by glyphosate at hypothalamiclevel that could affect fertility.