title: In vitro exposure to the organochlorine p,p'-DDE affects functional human sperm parameters.
abstract: Although no information exists regarding the levels of p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) on reproductive fluids of heavily exposed populations, they are possibly quite high given the serum levels reported so far. In these populations altered semen quality has been reported, although the direct effects of this DDT metabolite on crucial sperm parameters remain largely unexplored. With this in mind, a long-term in vitro incubation that better mimics the putative continuous exposure of spermatozoa to p,p'-DDE in the female reproductive tract in vivo was used. Before compromising sperm viability, continuous p,p'-DDE exposure remarkably decreased sperm motility, possibly due to the combined reduction in the proportion of sperm with high mitochondrial membrane potential and cellular ATP levels, all of which were clearly more affected at 50 and 100 μM p,p'-DDE. Moreover, 25 μM p,p'-DDE was also able to promote a decline in sperm with high MMP, however without significantly affecting motility. On the other hand, p,p'-DDE at the highest concentration strongly inhibited the process of capacitation following 24h of incubation. In conclusion, human sperm function is affected by continuous high p,p'-DDE exposure which may ultimately compromise male fertility. Given our previously findings that showed a non-regulated Ca(2+) entry in the presence of p,p'-DDE, we suggest that this organochlorine may promote mitochondrial Ca(2+) overload which may culminate in a general mitochondrial dysfunction and cellular ATP depletion, thus affecting sperm fertilizing potential. Our findings suggest a broader understanding of the non-genomic mechanism of p,p'-DDE action in human sperm.
authors.affiliation: Biology of Reproduction and Stem Cell Group, CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal; Department of Life Sciences, University of Coimbra, 3001-401 Coimbra, Portugal. Electronic address: renata@ua.pt.
authors.forename: Renata S
authors.initials: RS
authors.lastname: Tavares
authors.affiliation: Biology of Reproduction and Stem Cell Group, CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal. Electronic address: scgamaral@gmail.com.
authors.forename: Sandra
authors.initials: S
authors.lastname: Amaral
authors.affiliation: Biology of Reproduction and Stem Cell Group, CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal; Department of Life Sciences, University of Coimbra, 3001-401 Coimbra, Portugal. Electronic address: carlapaiva@gmail.com.
authors.forename: Carla
authors.initials: C
authors.lastname: Paiva
authors.affiliation: Biology of Reproduction and Stem Cell Group, CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal; Department of Life Sciences, University of Coimbra, 3001-401 Coimbra, Portugal. Electronic address: martabap@hotmail.com.
authors.forename: Marta
authors.initials: M
authors.lastname: Baptista
authors.affiliation: Biology of Reproduction and Stem Cell Group, CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal; Department of Life Sciences, University of Coimbra, 3001-401 Coimbra, Portugal. Electronic address: jramalho@ci.uc.pt.
authors.forename: João
authors.initials: J
authors.lastname: Ramalho-Santos
mesh_terms: D003633:Dichlorodiphenyl Dichloroethylene / Q000009:adverse effects*; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial; D055101:Semen Analysis; D013094:Spermatozoa / Q000187:drug effects*
chemical_list: D003633:Dichlorodiphenyl Dichloroethylene
keywords: Capacitation; Energy status; Human sperm function; Male fertility; Mitochondrial membrane potential; p,p′-DDE