title: Adult exposure to bisphenol A (BPA) in Wistar rats reduces sperm quality with disruption of the hypothalamic-pituitary-testicular axis.
abstract: Reproductive physiology involves complex biological processes that can be disrupted by exposure to environmental contaminants. The effects of bisphenol A (BPA) on spermatogenesis and sperm quality is still unclear. The objective of this study was to investigate the reproductive toxicity of BPA at dosages considered to be safe (5 or 25mg BPA/kg/day). We assessed multiple sperm parameters, the relative expression of genes involved in the central regulation of the hypothalamic-pituitary-testicular axis, and the serum concentrations of testosterone, estradiol, LH and FSH. BPA exposure reduced sperm production, reserves and transit time. Significant damage to the acrosomes and the plasma membrane with reduced mitochondrial activity and increased levels of defective spermatozoa may have compromised sperm function and caused faster movement through the epididymis. BPA exposure reduced the serum concentrations of testosterone, LH and FSH and increased the concentration of estradiol. The relative gene expression revealed an increase in gonadotropin releasing hormone receptor (Gnrhr), luteinizing hormone beta (Lhb), follicle stimulating hormone beta (Fshb), estrogen receptor beta (Esr2) and androgen receptor (Ar) transcripts in the pituitary and a reduction in estrogen receptor alpha (Esr1) transcripts in the hypothalamus. In this study, we demonstrated for the first time that adult male exposure to BPA caused a reduction in sperm production and specific functional parameters. The corresponding pattern of gene expression is indicative of an attempt by the pituitary to reestablish normal levels of LH, FSH and testosterone serum concentrations. In conclusion, these data suggest that at dosages previously considered nontoxic to reproductive function, BPA compromises the spermatozoa and disrupts the hypothalamic-pituitary-gonadal axis, causing a state of hypogonadotropic hypogonadism.
authors.affiliation: Laboratory of Reproductive Toxicology, Department of Pharmacy, State University of Centro-Oeste, Parana, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Wisniewski
authors.affiliation: Laboratory of Reproductive Toxicology, Department of Pharmacy, State University of Centro-Oeste, Parana, Brazil.
authors.forename: Renata M
authors.initials: RM
authors.lastname: Romano
authors.affiliation: Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp/EPM), São Paulo, SP, Brazil.
authors.forename: Marina M L
authors.initials: MM
authors.lastname: Kizys
authors.affiliation: Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp/EPM), São Paulo, SP, Brazil.
authors.forename: Kelen C
authors.initials: KC
authors.lastname: Oliveira
authors.affiliation: Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp/EPM), São Paulo, SP, Brazil.
authors.forename: Teresa
authors.initials: T
authors.lastname: Kasamatsu
authors.affiliation: Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp/EPM), São Paulo, SP, Brazil.
authors.forename: Gisele
authors.initials: G
authors.lastname: Giannocco
authors.affiliation: Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp/EPM), São Paulo, SP, Brazil.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Chiamolera
authors.affiliation: Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp/EPM), São Paulo, SP, Brazil.
authors.forename: Magnus R
authors.initials: MR
authors.lastname: Dias-da-Silva
authors.affiliation: Laboratory of Reproductive Toxicology, Department of Pharmacy, State University of Centro-Oeste, Parana, Brazil. Electronic address: maromano17@gmail.com.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Romano
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004822:Epididymis / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D011966:Receptors, LHRH / Q000235:genetics / Q000378:metabolism; D012098:Reproduction / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004958:Estradiol; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005640:Follicle Stimulating Hormone; D007986:Luteinizing Hormone; D010636:Phenols; D011944:Receptors, Androgen; D011966:Receptors, LHRH; D013739:Testosterone; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; Gene expression; Gonadotropins; Sperm function; Sperm production; Testosterone