• The dogma that AR activity is linearly related to AR CAG length has been challenged. • Only 2 o... more • The dogma that AR activity is linearly related to AR CAG length has been challenged. • Only 2 out of 21 reproductive makers are linearly related to AR CAG/GGN length. • Majority of reproductive markers are non-linearly associated with CAG/GGN length. • Non-linear associations are confirmed using flexible spline regression models.Recently the dogma that there is an inverse linear association between androgen receptor (AR) CAG and GGN polymorphisms and receptor activity has been challenged. We analysed the pattern of association between 21 male reproductive phenotypes and AR CAG/GGN repeat lengths in 557 proven-fertile men.A linear association was only found between sperm DNA fragmentation index (DFI) and CAG length, and between inhibin B and GGN length. Men with longer CAG then the reference (22–24), had higher oestradiol levels, whereas men with shorter CAG stretches had a higher DFI and a higher proportion of Fas-positive germ cells. Subjects with either short or long CAG had increased seminal levels of prostate-specific antigen and neutral α-glucosidase activity. Compared to men with the median GGN length of 23, those with shorter GGN repeats had higher levels of inhibin B, higher proportions of normal and progressive sperm, and a higher fraction of Fas-positive sperm, while men with longer GGN had higher oestradiol levels.These data indicate that at least for some markers of male reproductive function the association with CAG or GGN repeat length is curvilinear.
Fenarimol administered in one single oral dose of 125 or 62.5 mg kg-1 body wt. day-1, respectivel... more Fenarimol administered in one single oral dose of 125 or 62.5 mg kg-1 body wt. day-1, respectively, stimulated rat liver enlargement at a dose-independent rate. Three single doses of fenarimol produced dose-dependent liver growth, whereas five single doses caused no further increase in liver weight. This increase was accompanied by an increase in hepatic DNA synthesis and mitotic activity, with a peak on the first day after the beginning of the experiments. The increase in binuclear hepatocytes and signs of necrosis suggested that the hepatomitogenic effect reflected a compensatory hyperplasia. After both three and five single doses the hepatomitogenic effect was suppressed, as a result of tolerance development.
Abstract: Human exposure to environmental contaminants is ubiquitous and can affect individuals l... more Abstract: Human exposure to environmental contaminants is ubiquitous and can affect individuals living close to as well as remote from the sources of contaminants. Persistent organic pollutants (POPs) include polychlorinated dibenzo-p-dioxins/furans (PCDDs/PCDFs), polychlorinated biphenyls (PCBs) and certain pesticide residues. Exposure to POPs elicits a number of species-and tissue-specific toxic responses including effects on the reproductive-, immune-and thyroid system. Adverse effects have been ...
Bulletin of Environmental Contamination and Toxicology, 1997
Assuming that lactation may be an important factor in disposing organochlorine compounds from the... more Assuming that lactation may be an important factor in disposing organochlorine compounds from the woman’s body, an attempt has been made to answer how the number of deliveries and the following lactations affect the organochlorine compound levels excreted in the mother’s milk. The results from this study may also constitute a contribution to an overall discussion on infant exposure to
Bulletin of Environmental Contamination and Toxicology, 1997
Persistent organochlorine compounds were used in agriculture and industry for years. Their abilit... more Persistent organochlorine compounds were used in agriculture and industry for years. Their ability to accumulate in organisms constituting links of the food chain (Dewailly et al. 1993, Ludwicki and Góralczyk 1994) and a unique chemical stability made them a hazardous environmental contaminants. The metabolism and excretion of chlorinated hydrocarbons is a very slow process. One of the most important means
Bulletin of Environmental Contamination and Toxicology, 1990
The idea that inorganic mercury ingested in small quantiries with diet can be partly transformed ... more The idea that inorganic mercury ingested in small quantiries with diet can be partly transformed into methylmercutic gon (MeHg> bas been suggested by Edwards (igZ3) and Rowland (1984). Also out prev�8 studies gave the ergdente that the inorganic mercury tan be converted Into methylmercuric gon in various segments of gastrointestinal tract in the in vitro conditions (Ludwickl 1989). The conversion
Bulletin of Environmental Contamination and Toxicology, 1991
exane (HCH), hexachlorobenzene (HCB) and polychlor~nated biphenyls (PCBs) may pose toxicological ... more exane (HCH), hexachlorobenzene (HCB) and polychlor~nated biphenyls (PCBs) may pose toxicological and ecological impact due to their persistency in some biological compartments. Such chemicals as DDT, PCBs, HCH and HCB as well as some other inducers of drug metabolizing enzymes are also promoters in experimental hepatocarcinogenesis (Pitot et al. 1980). The relationship between shell thinning and the OC pesticide residues
Bulletin of Environmental Contamination and Toxicology, 1989
The to~~ic action of the mercury compounds and their bioavailability depends on the chemical stuc... more The to~~ic action of the mercury compounds and their bioavailability depends on the chemical stucture of the compound. It is we�9 known~ that mercurv compounds tan be transformed into metalic mercury or to alhyl mercur~ compounds in the environment. This transformation,
Archives of Environmental Contamination and Toxicology, 1999
This study was an attempt to identify if there are any trends in excretion of 1,2,3,4,5,6-hexachl... more This study was an attempt to identify if there are any trends in excretion of 1,2,3,4,5,6-hexachlorocyclohexane (HCH) isomers alpha-, beta-, and gamma-, hexachlorobenzene (HCB), [1,1,1-trichloro-2, 2-bis(4-chlorophenyl)ethane] (p,p'-DDT), [1,1-dichloro-2, 2-bis(4-chlorophenyl)ethane] (p,p'-DDD), [1,1-dichloro-2, 2-bis(4-chlorophenyl)ethylene] (p,p'-DDE), and polychlorinated biphenyls (PCBs) with human milk during lactation. The shortest lactation studied took 16 weeks, and the longest 84 weeks. Three hundred fifty-two milk samples, collected from each donor once a week, were examined. The analysis of the result showed individual differences in the excretion of the compounds. The findings from this study are not conclusive enough to claim that there are consistent trends showing a decrease or increase in the excretion of the compounds under examination. Thus, one cannot claim that the infants' exposure to those compounds decreases or increases as breast-feeding continues.
Occupational and environmental medicine, Jan 10, 2014
Numerous environmental contaminants have been linked to adverse reproductive health outcomes. How... more Numerous environmental contaminants have been linked to adverse reproductive health outcomes. However, the complex correlation structure of exposures and multiple testing issues limit the interpretation of existing evidence. Our objective was to identify, from a large set of contaminant exposures, exposure profiles associated with biomarkers of male reproductive function. In this cross-sectional study (n=602), male partners of pregnant women were enrolled between 2002 and 2004 during antenatal care visits in Greenland, Poland and Ukraine. Fifteen contaminants were detected in more than 70% of blood samples, including metabolites of di(2-ethylhexyl) and diisononyl phthalates (DEHP, DiNP), perfluoroalkyl acids, metals and organochlorines. Twenty-two reproductive biomarkers were assessed, including serum levels of reproductive hormones, markers of semen quality, sperm chromatin integrity, epididymal and accessory sex gland function, and Y:X chromosome ratio. We evaluated multipollutant...
Environmental health : a global access science source, 2005
Persistent organochlorine pollutants (POPs) may interfere with reproductive function but direct e... more Persistent organochlorine pollutants (POPs) may interfere with reproductive function but direct evidence in humans is very limited. Fertility was examined in four regions with contrasting blood levels of POPs. Pregnant women and their partners in Warsaw (Poland), Kharkiv (Ukraine) and Greenland were consecutively enrolled during antenatal visits. Swedish fishermen and their spouses were recruited separately and independently of current pregnancy. Lipid adjusted serum concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (DDE) were available for both partners. Time to pregnancy interviews were obtained among 2269 women and 798 men provided a semen sample. Inuits had high levels of both POP markers, Swedish fishermen were high in CB-153 but low in DDE, men from Kharkiv were high in DDE and low in CB-153 while men from Warsaw were low in CB-153 and had intermediate DDE levels. Compared to Warsaw couples, fecundabilit...
• The dogma that AR activity is linearly related to AR CAG length has been challenged. • Only 2 o... more • The dogma that AR activity is linearly related to AR CAG length has been challenged. • Only 2 out of 21 reproductive makers are linearly related to AR CAG/GGN length. • Majority of reproductive markers are non-linearly associated with CAG/GGN length. • Non-linear associations are confirmed using flexible spline regression models.Recently the dogma that there is an inverse linear association between androgen receptor (AR) CAG and GGN polymorphisms and receptor activity has been challenged. We analysed the pattern of association between 21 male reproductive phenotypes and AR CAG/GGN repeat lengths in 557 proven-fertile men.A linear association was only found between sperm DNA fragmentation index (DFI) and CAG length, and between inhibin B and GGN length. Men with longer CAG then the reference (22–24), had higher oestradiol levels, whereas men with shorter CAG stretches had a higher DFI and a higher proportion of Fas-positive germ cells. Subjects with either short or long CAG had increased seminal levels of prostate-specific antigen and neutral α-glucosidase activity. Compared to men with the median GGN length of 23, those with shorter GGN repeats had higher levels of inhibin B, higher proportions of normal and progressive sperm, and a higher fraction of Fas-positive sperm, while men with longer GGN had higher oestradiol levels.These data indicate that at least for some markers of male reproductive function the association with CAG or GGN repeat length is curvilinear.
Fenarimol administered in one single oral dose of 125 or 62.5 mg kg-1 body wt. day-1, respectivel... more Fenarimol administered in one single oral dose of 125 or 62.5 mg kg-1 body wt. day-1, respectively, stimulated rat liver enlargement at a dose-independent rate. Three single doses of fenarimol produced dose-dependent liver growth, whereas five single doses caused no further increase in liver weight. This increase was accompanied by an increase in hepatic DNA synthesis and mitotic activity, with a peak on the first day after the beginning of the experiments. The increase in binuclear hepatocytes and signs of necrosis suggested that the hepatomitogenic effect reflected a compensatory hyperplasia. After both three and five single doses the hepatomitogenic effect was suppressed, as a result of tolerance development.
Abstract: Human exposure to environmental contaminants is ubiquitous and can affect individuals l... more Abstract: Human exposure to environmental contaminants is ubiquitous and can affect individuals living close to as well as remote from the sources of contaminants. Persistent organic pollutants (POPs) include polychlorinated dibenzo-p-dioxins/furans (PCDDs/PCDFs), polychlorinated biphenyls (PCBs) and certain pesticide residues. Exposure to POPs elicits a number of species-and tissue-specific toxic responses including effects on the reproductive-, immune-and thyroid system. Adverse effects have been ...
Bulletin of Environmental Contamination and Toxicology, 1997
Assuming that lactation may be an important factor in disposing organochlorine compounds from the... more Assuming that lactation may be an important factor in disposing organochlorine compounds from the woman’s body, an attempt has been made to answer how the number of deliveries and the following lactations affect the organochlorine compound levels excreted in the mother’s milk. The results from this study may also constitute a contribution to an overall discussion on infant exposure to
Bulletin of Environmental Contamination and Toxicology, 1997
Persistent organochlorine compounds were used in agriculture and industry for years. Their abilit... more Persistent organochlorine compounds were used in agriculture and industry for years. Their ability to accumulate in organisms constituting links of the food chain (Dewailly et al. 1993, Ludwicki and Góralczyk 1994) and a unique chemical stability made them a hazardous environmental contaminants. The metabolism and excretion of chlorinated hydrocarbons is a very slow process. One of the most important means
Bulletin of Environmental Contamination and Toxicology, 1990
The idea that inorganic mercury ingested in small quantiries with diet can be partly transformed ... more The idea that inorganic mercury ingested in small quantiries with diet can be partly transformed into methylmercutic gon (MeHg> bas been suggested by Edwards (igZ3) and Rowland (1984). Also out prev�8 studies gave the ergdente that the inorganic mercury tan be converted Into methylmercuric gon in various segments of gastrointestinal tract in the in vitro conditions (Ludwickl 1989). The conversion
Bulletin of Environmental Contamination and Toxicology, 1991
exane (HCH), hexachlorobenzene (HCB) and polychlor~nated biphenyls (PCBs) may pose toxicological ... more exane (HCH), hexachlorobenzene (HCB) and polychlor~nated biphenyls (PCBs) may pose toxicological and ecological impact due to their persistency in some biological compartments. Such chemicals as DDT, PCBs, HCH and HCB as well as some other inducers of drug metabolizing enzymes are also promoters in experimental hepatocarcinogenesis (Pitot et al. 1980). The relationship between shell thinning and the OC pesticide residues
Bulletin of Environmental Contamination and Toxicology, 1989
The to~~ic action of the mercury compounds and their bioavailability depends on the chemical stuc... more The to~~ic action of the mercury compounds and their bioavailability depends on the chemical stucture of the compound. It is we�9 known~ that mercurv compounds tan be transformed into metalic mercury or to alhyl mercur~ compounds in the environment. This transformation,
Archives of Environmental Contamination and Toxicology, 1999
This study was an attempt to identify if there are any trends in excretion of 1,2,3,4,5,6-hexachl... more This study was an attempt to identify if there are any trends in excretion of 1,2,3,4,5,6-hexachlorocyclohexane (HCH) isomers alpha-, beta-, and gamma-, hexachlorobenzene (HCB), [1,1,1-trichloro-2, 2-bis(4-chlorophenyl)ethane] (p,p'-DDT), [1,1-dichloro-2, 2-bis(4-chlorophenyl)ethane] (p,p'-DDD), [1,1-dichloro-2, 2-bis(4-chlorophenyl)ethylene] (p,p'-DDE), and polychlorinated biphenyls (PCBs) with human milk during lactation. The shortest lactation studied took 16 weeks, and the longest 84 weeks. Three hundred fifty-two milk samples, collected from each donor once a week, were examined. The analysis of the result showed individual differences in the excretion of the compounds. The findings from this study are not conclusive enough to claim that there are consistent trends showing a decrease or increase in the excretion of the compounds under examination. Thus, one cannot claim that the infants' exposure to those compounds decreases or increases as breast-feeding continues.
Occupational and environmental medicine, Jan 10, 2014
Numerous environmental contaminants have been linked to adverse reproductive health outcomes. How... more Numerous environmental contaminants have been linked to adverse reproductive health outcomes. However, the complex correlation structure of exposures and multiple testing issues limit the interpretation of existing evidence. Our objective was to identify, from a large set of contaminant exposures, exposure profiles associated with biomarkers of male reproductive function. In this cross-sectional study (n=602), male partners of pregnant women were enrolled between 2002 and 2004 during antenatal care visits in Greenland, Poland and Ukraine. Fifteen contaminants were detected in more than 70% of blood samples, including metabolites of di(2-ethylhexyl) and diisononyl phthalates (DEHP, DiNP), perfluoroalkyl acids, metals and organochlorines. Twenty-two reproductive biomarkers were assessed, including serum levels of reproductive hormones, markers of semen quality, sperm chromatin integrity, epididymal and accessory sex gland function, and Y:X chromosome ratio. We evaluated multipollutant...
Environmental health : a global access science source, 2005
Persistent organochlorine pollutants (POPs) may interfere with reproductive function but direct e... more Persistent organochlorine pollutants (POPs) may interfere with reproductive function but direct evidence in humans is very limited. Fertility was examined in four regions with contrasting blood levels of POPs. Pregnant women and their partners in Warsaw (Poland), Kharkiv (Ukraine) and Greenland were consecutively enrolled during antenatal visits. Swedish fishermen and their spouses were recruited separately and independently of current pregnancy. Lipid adjusted serum concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (DDE) were available for both partners. Time to pregnancy interviews were obtained among 2269 women and 798 men provided a semen sample. Inuits had high levels of both POP markers, Swedish fishermen were high in CB-153 but low in DDE, men from Kharkiv were high in DDE and low in CB-153 while men from Warsaw were low in CB-153 and had intermediate DDE levels. Compared to Warsaw couples, fecundabilit...
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