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Sperm Y:X chromosome ratio and androgen response in men exposed to environmental pollutants

Kvist, Linus LU (2015) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2015:44.
Abstract
The last several decades have seen an increase in male infertility concomitant with a decline in the birth sex ratio. The conditions are believed to be linked to increased exposure to endocrine disrupting chemicals (EDCs), including the persistent organic pollutants or lifestyle factors e.g. smoking. The mechanism behind the lowered birth sex ratio is unknown, but might be due to an EDC-induced skewing of the proportions of Y to X chromosome bearing sperms.

The aims of this thesis were: to elucidate possible associations between the sperm Y:X ratio and EDCs in several highly exposed populations, to evaluate any relationships that might exist between the Y:X ratio and sperm parameters in subfertile men, and to investigate the... (More)
The last several decades have seen an increase in male infertility concomitant with a decline in the birth sex ratio. The conditions are believed to be linked to increased exposure to endocrine disrupting chemicals (EDCs), including the persistent organic pollutants or lifestyle factors e.g. smoking. The mechanism behind the lowered birth sex ratio is unknown, but might be due to an EDC-induced skewing of the proportions of Y to X chromosome bearing sperms.

The aims of this thesis were: to elucidate possible associations between the sperm Y:X ratio and EDCs in several highly exposed populations, to evaluate any relationships that might exist between the Y:X ratio and sperm parameters in subfertile men, and to investigate the effect of smoking on androgen regulation in vivo as well as in vitro.

The sperm sex chromosome ratio was investigated by fluorescent in situ hybridization (FISH) in n=449 men from the Faroe Islands and compared to n=414 men from Greenland, Ukraine and Poland. Infertile men n=190 were enrolled at a fertility clinic in Denmark and androgenicity in smoking men was measured in n=2156 men recruited for several previous epidemiological studies. The effect of smoking was assessed in a reporter system with the prostate specific antigen promoter driving a luciferase gene, in the presence or absence of various concentrations of the cigarette smoke constituent Benzo[α]Pyrene (BaP).

In men from the Faroe Islands, the Y:X ratio was lower than in other highly exposed populations and a negative association between the sperm sex chromosome ratio and both dichlorodiphenyl dichloroethane (DDE) and selected polychlorinated biphenyls (PCBs) in the somewhat older, proven fertile men was found. A positive trend between the Y:X ratio and perfuorooctane sulfonate (PFOS) in a combined population of men from Greenland, Ukraine and Poland was found. The opposite association was observed in the Greenland Inuit alone. In subfertile men, a positive association between the Y:X ratio and progressive motility was noted. In two cohorts of smoking men, positive trends between groups of men with increasing exposure to cigarette smoke and androgen insensitivity was found. The in vitro experiments showed a significant deactivation of the AR at the highest BaP concentration.

To conclude, high concentrations of EDCs influence the Y:X ratio in highly exposed populations i.e. men from Greenland and the Faroe Islands. The inter-population differences in Y:X ratio might be genetic or due to lifestyle factors such as diet. Men with low progressive motility had lower Y:X ratio, possibly explaining the low birth sex ratio seen following intra cytoplasmic sperm injection. Indications that smoking has adverse effects on the androgenicity were observed both in vivo and in vitro. (Less)
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author
supervisor
opponent
  • Professor Söder, Olle, Department of women's and children's health, division of pediatric endocrinology, Karolinska institutet Stockholm, Sweden
organization
publishing date
type
Thesis
publication status
published
subject
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2015:44
pages
83 pages
publisher
Institutionen för translationell medicin
defense location
Patologens aula, Jan Waldenströms gata 59, ing 78, Skånes Universitetssjukhus i Malmö
defense date
2015-05-08 13:00
ISSN
1652-8220
ISBN
978-91-7619-123-1
language
English
LU publication?
yes
id
afd81cb5-fb60-4c6c-90ee-5c0ea97c0e78 (old id 5268138)
date added to LUP
2015-04-13 09:35:26
date last changed
2016-09-19 08:44:50
@phdthesis{afd81cb5-fb60-4c6c-90ee-5c0ea97c0e78,
  abstract     = {The last several decades have seen an increase in male infertility concomitant with a decline in the birth sex ratio. The conditions are believed to be linked to increased exposure to endocrine disrupting chemicals (EDCs), including the persistent organic pollutants or lifestyle factors e.g. smoking. The mechanism behind the lowered birth sex ratio is unknown, but might be due to an EDC-induced skewing of the proportions of Y to X chromosome bearing sperms. <br/><br>
The aims of this thesis were: to elucidate possible associations between the sperm Y:X ratio and EDCs in several highly exposed populations, to evaluate any relationships that might exist between the Y:X ratio and sperm parameters in subfertile men, and to investigate the effect of smoking on androgen regulation in vivo as well as in vitro. <br/><br>
The sperm sex chromosome ratio was investigated by fluorescent in situ hybridization (FISH) in n=449 men from the Faroe Islands and compared to n=414 men from Greenland, Ukraine and Poland. Infertile men n=190 were enrolled at a fertility clinic in Denmark and androgenicity in smoking men was measured in n=2156 men recruited for several previous epidemiological studies. The effect of smoking was assessed in a reporter system with the prostate specific antigen promoter driving a luciferase gene, in the presence or absence of various concentrations of the cigarette smoke constituent Benzo[α]Pyrene (BaP).<br/><br>
In men from the Faroe Islands, the Y:X ratio was lower than in other highly exposed populations and a negative association between the sperm sex chromosome ratio and both dichlorodiphenyl dichloroethane (DDE) and selected polychlorinated biphenyls (PCBs) in the somewhat older, proven fertile men was found. A positive trend between the Y:X ratio and perfuorooctane sulfonate (PFOS) in a combined population of men from Greenland, Ukraine and Poland was found. The opposite association was observed in the Greenland Inuit alone. In subfertile men, a positive association between the Y:X ratio and progressive motility was noted. In two cohorts of smoking men, positive trends between groups of men with increasing exposure to cigarette smoke and androgen insensitivity was found. The in vitro experiments showed a significant deactivation of the AR at the highest BaP concentration.<br/><br>
To conclude, high concentrations of EDCs influence the Y:X ratio in highly exposed populations i.e. men from Greenland and the Faroe Islands. The inter-population differences in Y:X ratio might be genetic or due to lifestyle factors such as diet. Men with low progressive motility had lower Y:X ratio, possibly explaining the low birth sex ratio seen following intra cytoplasmic sperm injection. Indications that smoking has adverse effects on the androgenicity were observed both in vivo and in vitro.},
  author       = {Kvist, Linus},
  isbn         = {978-91-7619-123-1},
  issn         = {1652-8220},
  language     = {eng},
  pages        = {83},
  publisher    = {Institutionen för translationell medicin},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Sperm Y:X chromosome ratio and androgen response in men exposed to environmental pollutants},
  volume       = {2015:44},
  year         = {2015},
}