title: The Effects of Chronic Lifelong Activation of the AHR Pathway by Industrial Chemical Pollutants on Female Human Reproduction.
abstract: Environmental chemicals, such as heavy metals, affect female reproductive function. A biological sensor of the signals of many toxic chemical compounds seems to be the aryl hydrocarbon receptor (AHR). Previous studies demonstrated the environmental of heavy metals in Taranto city (Italy), an area that has been influenced by anthropogenic factors such as industrial activities and waste treatments since 1986. However, the impact of these elements on female fertility in this geographic area has never been analyzed. Thus, in the present study, we evaluated the AHR pathway, sex steroid receptor pattern and apoptotic process in granulosa cells (GCs) retrieved from 30 women, born and living in Taranto, and 30 women who are living in non-contaminated areas (control group), who were undergoing in vitro fertilization (IVF) protocol. In follicular fluids (FFs) of both groups the toxic and essential heavy metals, such as chromiun (Cr), Manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), cadmium (Cd) and lead (Pb), were also analyzed. Higher levels of Cr, Fe, Zn and Pb were found in the FFs of the women from Taranto as compared to the control group, as were the levels of AHR and AHR-dependent cytochrome P450 1A1 and 1B1; while CYP19A1 expression was decreased. The anti-apoptotic process found in the GCs of women fromTaranto was associated with the highest levels of progesterone receptor membrane component 1 (PGRMC1), a novel progesterone receptor, the expression of which is subjected to AHR activated by its highest affinity ligands (e.g., dioxins) or indirectly by other environmental pollutants, such as heavy metals. In conclusion, decreased production of estradiol and decreased number of retrieved mature oocytes found in women from Taranto could be due to chronic exposure to heavy metals, in particular to Cr and Pb.
authors.affiliation: Laboratory of Cellular and Molecular Biology, Dept. Clinical Pathology, National Institute for Digestive Diseases, IRCCS "Saverio de Bellis", via Turi 27, 70013, Castellana Grotte (BA), Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Cavallini
authors.affiliation: Laboratory of Cellular and Molecular Biology, Dept. Clinical Pathology, National Institute for Digestive Diseases, IRCCS "Saverio de Bellis", via Turi 27, 70013, Castellana Grotte (BA), Italy.
authors.forename: Catia
authors.initials: C
authors.lastname: Lippolis
authors.affiliation: Unit of Pathophysiology of Human Reproduction and Gametes Cryopreservation, Dept. of General Surgery, Gynecology, Obstetrics and Anesthesiology, University Hospital of Bari, Consorziale, Policlinico. piazza Giulio Cesare 11, 70124, Bari, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Vacca
authors.affiliation: Unit of Pathophysiology of Human Reproduction and Gametes Cryopreservation, Dept. of General Surgery, Gynecology, Obstetrics and Anesthesiology, University Hospital of Bari, Consorziale, Policlinico. piazza Giulio Cesare 11, 70124, Bari, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Nardelli
authors.affiliation: Dept. of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari "A. Moro", via E. Orabona 4, 70125, Bari, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Castegna
authors.affiliation: Dept. of Chemistry, University of Bari "A. Moro", via E. Orabona 4, 70125, Bari, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Arnesano
authors.affiliation: Laboratory of Cellular and Molecular Biology, Dept. Clinical Pathology, National Institute for Digestive Diseases, IRCCS "Saverio de Bellis", via Turi 27, 70013, Castellana Grotte (BA), Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Carella
authors.affiliation: Unit of Pathophysiology of Human Reproduction and Gametes Cryopreservation, Dept. of General Surgery, Gynecology, Obstetrics and Anesthesiology, University Hospital of Bari, Consorziale, Policlinico. piazza Giulio Cesare 11, 70124, Bari, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Depalo
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D001141:Aromatase / Q000032:analysis; D015153:Blotting, Western; D016022:Case-Control Studies; D004785:Environmental Pollutants / Q000009:adverse effects*; D005260:Female; D015571:Follicular Fluid / Q000737:chemistry; D006107:Granulosa Cells / Q000737:chemistry / Q000187:drug effects*; D006801:Humans; D007558:Italy; D008565:Membrane Proteins / Q000032:analysis; D019216:Metals, Heavy / Q000032:analysis; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects* / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis
chemical_list: D004785:Environmental Pollutants; D008565:Membrane Proteins; D019216:Metals, Heavy; C115296:PGRMC1 protein, human; D018336:Receptors, Aryl Hydrocarbon; D018160:Receptors, Cytoplasmic and Nuclear; D011980:Receptors, Progesterone; D001141:Aromatase