ENVIRONMENTAL CONTAMINANTS AND SPERM Y:X CHROMOSOME RATIO. Impact of androgen- and dioxin-related effects in vivo and in vitro.

Tarmo Tiido

ENVIRONMENTAL CONTAMINANTS AND SPERM Y:X CHROMOSOME RATIO. Impact of androgen- and dioxin-related effects in vivo and in vitro.

Tarmo Tiido

Reproductive medicine, Malmö

Research output: Thesis › Doctoral Thesis (compilation)

Abstract

During the last decades, there has been concern that the environmental contaminants, such as POPs, may contribute to sex ratio changes in offspring of exposed populations. Accidental exposure to TCDD has been shown to be associated with fewer sons in men who were exposed in adolescence or earlier in life. However, it is not known whether POPs could change the proportion of X- and Y-sperm. A variety of studies have indicated that POPs possess sex steroid-mimicking actions and/or AHR binding affinity. The aim of this thesis was to examine whether 1) the exposure to the POPs affects sperm Y:X ratio; 2) the endocrine disrupting action of POPs, in relation to observed changes in sperm sex chromosome ratio, may be modulated by genes involved in androgen and dioxin-mediated pathways; and 3) the functional interaction between AHR and the AR, which may play a part in regulation of sperm Y:X ratio, occurs in cultured Sertoli cells.

The current study indicates that exposure to POPs may be involved in changing the proportion of Y-sperm. However, these findings were subject to modification, most likely due to varying exposure profiles and exposure levels, as indicated by diverging serum concentrations of CB-153 and p,p´-DDE in different cohorts (Sweden, Greenland, Warsaw and Kharkiv) studied. Moreover, our findings lend support to the notion that polymorphisms in genes involved in androgen and dioxin-related pathways may predispose to augmented effects of POPs in increasing the sperm Y:X ratio. Thus, p,p´-DDE levels were associated with Y-sperm proportion in Swedish fishermen carrying <22 CAG repeats in the AR and the AHRR P185A G-allele, but not in those missing one or both of these variants. We obtained, however, no evidence unambiguously demonstrating the mechanistic action of TCDD in interfering with androgen-dependent Pem reporter gene transcription in the SK11 Sertoli cells. A larger series of experiments or another study design may be required before any definitive conclusions can be drawn regarding the anti-androgenic capability of TCDD in testis.

In conclusion, high exposure to POPs could affect sperm sex chromosome ratio. These findings were subject to inter-country differences, likely dependent on differing blood levels and composition of POPs. The AR/AHRR genotypes may act as effect modifiers predisposing to sperm sex ratio changes. The significance of androgen disrupting capability of AHR ligands in androgen-responsive cells of testis, however, waits for further studies.

Original language	English
Qualification	Doctor
Awarding Institution	Reproductive medicine, Malmö
Supervisors/Advisors	Giwercman, Aleksander, Supervisor
Award date	2007 May 16
Publisher	Department of Clinical Sciences, Lund University
ISBN (Print)	978-91-85559-51-0
Publication status	Published - 2007

Bibliographical note

Defence details

Date: 2007-05-16
Time: 09:00
Place: CRC Aula, Clinical Research Centre, Malmö University Hospital, entrance 72

External reviewer(s)

Name: Toppari, Jorma
Title: Professor
Affiliation: Department of Pediatrics and Physiology, University of Turku, Finland

---

<div class="article_info">T Tiido, A Rignell-Hydbom, B Jönsson, YL Giwercman, L Rylander, L Hagmar and A Giwercman. <span class="article_issue_date">2005</span>. <span class="article_title">Exposure to persistent organochlorine pollutants associates with human sperm Y:X chromosome ratio.</span> <span class="journal_series_title">Human Reproduction</span>, <span class="journal_volume">vol 20</span> <span class="journal_pages">pp 1903-1909</span>.</div>
<div class="article_info">T Tiido, A Rignell-Hydbom, BAG Jönsson, YL Giwercman, HS Pedersen, B Wojtyniak, J Ludwicki, V Lesovoy, V Zvezday, M Spano, GC Manicardi, D Bizzaro, EC Bonefeld-Jørgensen, G Toft, JP Bonde, L Rylander, L Hagmar and A Giwercman. <span class="article_issue_date">2006</span>. <span class="article_title">Impact of PCB and p,p´-DDE contaminants on human sperm Y:X chromosome ratio: studies in three European populations and the Inuit population in Greenland.</span> <span class="journal_series_title">Environmental Health Perspectives</span>, <span class="journal_volume">vol 114</span> <span class="journal_pages">pp 718-724</span>.</div>
<div class="article_info">T Tiido, A Rignell-Hydbom, BAG Jönsson, L Rylander, A Giwercman and YL Giwercman. <span class="article_issue_date"></span>. <span class="article_title">Modifying effect of the AR gene trinucleotide repeats and SNPs in the AHR and AHRR genes on the association between persistent organohalogen pollutant exposure and human sperm Y:X ratio.</span> <span class="journal_series_title">Mol Hum Reprod</span>, (inpress)</div>
<div class="article_info">T Tiido and YL Giwercman. <span class="article_issue_date"></span>. <span class="article_title">Effect of dioxin on androgen-induced Pem trans-activation in Sertoli cells.</span> (manuscript)</div>

Subject classification (UKÄ)

Gynaecology, Obstetrics and Reproductive Medicine

Free keywords

AR
polymorphisms
Sertoli cell
endocrine disruption
inhibitory cross-talk
Biomedicinska vetenskaper
Biomedical sciences
AHR
sperm Y:X chromosome ratio
sex ratio
POPs
TCDD

Cite this

@phdthesis{6eeade58932f42f6826e9f71cd5a2efb,

title = "ENVIRONMENTAL CONTAMINANTS AND SPERM Y:X CHROMOSOME RATIO. Impact of androgen- and dioxin-related effects in vivo and in vitro.",

abstract = "During the last decades, there has been concern that the environmental contaminants, such as POPs, may contribute to sex ratio changes in offspring of exposed populations. Accidental exposure to TCDD has been shown to be associated with fewer sons in men who were exposed in adolescence or earlier in life. However, it is not known whether POPs could change the proportion of X- and Y-sperm. A variety of studies have indicated that POPs possess sex steroid-mimicking actions and/or AHR binding affinity. The aim of this thesis was to examine whether 1) the exposure to the POPs affects sperm Y:X ratio; 2) the endocrine disrupting action of POPs, in relation to observed changes in sperm sex chromosome ratio, may be modulated by genes involved in androgen and dioxin-mediated pathways; and 3) the functional interaction between AHR and the AR, which may play a part in regulation of sperm Y:X ratio, occurs in cultured Sertoli cells. The current study indicates that exposure to POPs may be involved in changing the proportion of Y-sperm. However, these findings were subject to modification, most likely due to varying exposure profiles and exposure levels, as indicated by diverging serum concentrations of CB-153 and p,p´-DDE in different cohorts (Sweden, Greenland, Warsaw and Kharkiv) studied. Moreover, our findings lend support to the notion that polymorphisms in genes involved in androgen and dioxin-related pathways may predispose to augmented effects of POPs in increasing the sperm Y:X ratio. Thus, p,p´-DDE levels were associated with Y-sperm proportion in Swedish fishermen carrying <22 CAG repeats in the AR and the AHRR P185A G-allele, but not in those missing one or both of these variants. We obtained, however, no evidence unambiguously demonstrating the mechanistic action of TCDD in interfering with androgen-dependent Pem reporter gene transcription in the SK11 Sertoli cells. A larger series of experiments or another study design may be required before any definitive conclusions can be drawn regarding the anti-androgenic capability of TCDD in testis. In conclusion, high exposure to POPs could affect sperm sex chromosome ratio. These findings were subject to inter-country differences, likely dependent on differing blood levels and composition of POPs. The AR/AHRR genotypes may act as effect modifiers predisposing to sperm sex ratio changes. The significance of androgen disrupting capability of AHR ligands in androgen-responsive cells of testis, however, waits for further studies.",

keywords = "AR, polymorphisms, Sertoli cell, endocrine disruption, inhibitory cross-talk, Biomedicinska vetenskaper, Biomedical sciences, AHR, sperm Y:X chromosome ratio, sex ratio, POPs, TCDD",

author = "Tarmo Tiido",

note = "Defence details Date: 2007-05-16 Time: 09:00 Place: CRC Aula, Clinical Research Centre, Malm{\"o} University Hospital, entrance 72 External reviewer(s) Name: Toppari, Jorma Title: Professor Affiliation: Department of Pediatrics and Physiology, University of Turku, Finland --- <div class={"}article_info{"}>T Tiido, A Rignell-Hydbom, B J{\"o}nsson, YL Giwercman, L Rylander, L Hagmar and A Giwercman. <span class={"}article_issue_date{"}>2005</span>. <span class={"}article_title{"}>Exposure to persistent organochlorine pollutants associates with human sperm Y:X chromosome ratio.</span> <span class={"}journal_series_title{"}>Human Reproduction</span>, <span class={"}journal_volume{"}>vol 20</span> <span class={"}journal_pages{"}>pp 1903-1909</span>.</div> <div class={"}article_info{"}>T Tiido, A Rignell-Hydbom, BAG J{\"o}nsson, YL Giwercman, HS Pedersen, B Wojtyniak, J Ludwicki, V Lesovoy, V Zvezday, M Spano, GC Manicardi, D Bizzaro, EC Bonefeld-J{\o}rgensen, G Toft, JP Bonde, L Rylander, L Hagmar and A Giwercman. <span class={"}article_issue_date{"}>2006</span>. <span class={"}article_title{"}>Impact of PCB and p,p´-DDE contaminants on human sperm Y:X chromosome ratio: studies in three European populations and the Inuit population in Greenland.</span> <span class={"}journal_series_title{"}>Environmental Health Perspectives</span>, <span class={"}journal_volume{"}>vol 114</span> <span class={"}journal_pages{"}>pp 718-724</span>.</div> <div class={"}article_info{"}>T Tiido, A Rignell-Hydbom, BAG J{\"o}nsson, L Rylander, A Giwercman and YL Giwercman. <span class={"}article_issue_date{"}></span>. <span class={"}article_title{"}>Modifying effect of the AR gene trinucleotide repeats and SNPs in the AHR and AHRR genes on the association between persistent organohalogen pollutant exposure and human sperm Y:X ratio.</span> <span class={"}journal_series_title{"}>Mol Hum Reprod</span>, (inpress)</div> <div class={"}article_info{"}>T Tiido and YL Giwercman. <span class={"}article_issue_date{"}></span>. <span class={"}article_title{"}>Effect of dioxin on androgen-induced Pem trans-activation in Sertoli cells.</span> (manuscript)</div>",

year = "2007",

language = "English",

isbn = "978-91-85559-51-0",

series = "Lund University Faculty of Medicine Doctoral Dissertation Series ",

publisher = "Department of Clinical Sciences, Lund University",

type = "Doctoral Thesis (compilation)",

school = "Reproductive medicine, Malm{\"o}",

}

TY - THES

T1 - ENVIRONMENTAL CONTAMINANTS AND SPERM Y:X CHROMOSOME RATIO. Impact of androgen- and dioxin-related effects in vivo and in vitro.

AU - Tiido, Tarmo

N1 - Defence details Date: 2007-05-16 Time: 09:00 Place: CRC Aula, Clinical Research Centre, Malmö University Hospital, entrance 72 External reviewer(s) Name: Toppari, Jorma Title: Professor Affiliation: Department of Pediatrics and Physiology, University of Turku, Finland --- <div class="article_info">T Tiido, A Rignell-Hydbom, B Jönsson, YL Giwercman, L Rylander, L Hagmar and A Giwercman. <span class="article_issue_date">2005</span>. <span class="article_title">Exposure to persistent organochlorine pollutants associates with human sperm Y:X chromosome ratio.</span> <span class="journal_series_title">Human Reproduction</span>, <span class="journal_volume">vol 20</span> <span class="journal_pages">pp 1903-1909</span>.</div> <div class="article_info">T Tiido, A Rignell-Hydbom, BAG Jönsson, YL Giwercman, HS Pedersen, B Wojtyniak, J Ludwicki, V Lesovoy, V Zvezday, M Spano, GC Manicardi, D Bizzaro, EC Bonefeld-Jørgensen, G Toft, JP Bonde, L Rylander, L Hagmar and A Giwercman. <span class="article_issue_date">2006</span>. <span class="article_title">Impact of PCB and p,p´-DDE contaminants on human sperm Y:X chromosome ratio: studies in three European populations and the Inuit population in Greenland.</span> <span class="journal_series_title">Environmental Health Perspectives</span>, <span class="journal_volume">vol 114</span> <span class="journal_pages">pp 718-724</span>.</div> <div class="article_info">T Tiido, A Rignell-Hydbom, BAG Jönsson, L Rylander, A Giwercman and YL Giwercman. <span class="article_issue_date"></span>. <span class="article_title">Modifying effect of the AR gene trinucleotide repeats and SNPs in the AHR and AHRR genes on the association between persistent organohalogen pollutant exposure and human sperm Y:X ratio.</span> <span class="journal_series_title">Mol Hum Reprod</span>, (inpress)</div> <div class="article_info">T Tiido and YL Giwercman. <span class="article_issue_date"></span>. <span class="article_title">Effect of dioxin on androgen-induced Pem trans-activation in Sertoli cells.</span> (manuscript)</div>

PY - 2007

Y1 - 2007

N2 - During the last decades, there has been concern that the environmental contaminants, such as POPs, may contribute to sex ratio changes in offspring of exposed populations. Accidental exposure to TCDD has been shown to be associated with fewer sons in men who were exposed in adolescence or earlier in life. However, it is not known whether POPs could change the proportion of X- and Y-sperm. A variety of studies have indicated that POPs possess sex steroid-mimicking actions and/or AHR binding affinity. The aim of this thesis was to examine whether 1) the exposure to the POPs affects sperm Y:X ratio; 2) the endocrine disrupting action of POPs, in relation to observed changes in sperm sex chromosome ratio, may be modulated by genes involved in androgen and dioxin-mediated pathways; and 3) the functional interaction between AHR and the AR, which may play a part in regulation of sperm Y:X ratio, occurs in cultured Sertoli cells. The current study indicates that exposure to POPs may be involved in changing the proportion of Y-sperm. However, these findings were subject to modification, most likely due to varying exposure profiles and exposure levels, as indicated by diverging serum concentrations of CB-153 and p,p´-DDE in different cohorts (Sweden, Greenland, Warsaw and Kharkiv) studied. Moreover, our findings lend support to the notion that polymorphisms in genes involved in androgen and dioxin-related pathways may predispose to augmented effects of POPs in increasing the sperm Y:X ratio. Thus, p,p´-DDE levels were associated with Y-sperm proportion in Swedish fishermen carrying <22 CAG repeats in the AR and the AHRR P185A G-allele, but not in those missing one or both of these variants. We obtained, however, no evidence unambiguously demonstrating the mechanistic action of TCDD in interfering with androgen-dependent Pem reporter gene transcription in the SK11 Sertoli cells. A larger series of experiments or another study design may be required before any definitive conclusions can be drawn regarding the anti-androgenic capability of TCDD in testis. In conclusion, high exposure to POPs could affect sperm sex chromosome ratio. These findings were subject to inter-country differences, likely dependent on differing blood levels and composition of POPs. The AR/AHRR genotypes may act as effect modifiers predisposing to sperm sex ratio changes. The significance of androgen disrupting capability of AHR ligands in androgen-responsive cells of testis, however, waits for further studies.

AB - During the last decades, there has been concern that the environmental contaminants, such as POPs, may contribute to sex ratio changes in offspring of exposed populations. Accidental exposure to TCDD has been shown to be associated with fewer sons in men who were exposed in adolescence or earlier in life. However, it is not known whether POPs could change the proportion of X- and Y-sperm. A variety of studies have indicated that POPs possess sex steroid-mimicking actions and/or AHR binding affinity. The aim of this thesis was to examine whether 1) the exposure to the POPs affects sperm Y:X ratio; 2) the endocrine disrupting action of POPs, in relation to observed changes in sperm sex chromosome ratio, may be modulated by genes involved in androgen and dioxin-mediated pathways; and 3) the functional interaction between AHR and the AR, which may play a part in regulation of sperm Y:X ratio, occurs in cultured Sertoli cells. The current study indicates that exposure to POPs may be involved in changing the proportion of Y-sperm. However, these findings were subject to modification, most likely due to varying exposure profiles and exposure levels, as indicated by diverging serum concentrations of CB-153 and p,p´-DDE in different cohorts (Sweden, Greenland, Warsaw and Kharkiv) studied. Moreover, our findings lend support to the notion that polymorphisms in genes involved in androgen and dioxin-related pathways may predispose to augmented effects of POPs in increasing the sperm Y:X ratio. Thus, p,p´-DDE levels were associated with Y-sperm proportion in Swedish fishermen carrying <22 CAG repeats in the AR and the AHRR P185A G-allele, but not in those missing one or both of these variants. We obtained, however, no evidence unambiguously demonstrating the mechanistic action of TCDD in interfering with androgen-dependent Pem reporter gene transcription in the SK11 Sertoli cells. A larger series of experiments or another study design may be required before any definitive conclusions can be drawn regarding the anti-androgenic capability of TCDD in testis. In conclusion, high exposure to POPs could affect sperm sex chromosome ratio. These findings were subject to inter-country differences, likely dependent on differing blood levels and composition of POPs. The AR/AHRR genotypes may act as effect modifiers predisposing to sperm sex ratio changes. The significance of androgen disrupting capability of AHR ligands in androgen-responsive cells of testis, however, waits for further studies.

KW - AR

KW - polymorphisms

KW - Sertoli cell

KW - endocrine disruption

KW - inhibitory cross-talk

KW - Biomedicinska vetenskaper

KW - Biomedical sciences

KW - AHR

KW - sperm Y:X chromosome ratio

KW - sex ratio

KW - POPs

KW - TCDD

M3 - Doctoral Thesis (compilation)

SN - 978-91-85559-51-0

T3 - Lund University Faculty of Medicine Doctoral Dissertation Series

PB - Department of Clinical Sciences, Lund University

ER -

ENVIRONMENTAL CONTAMINANTS AND SPERM Y:X CHROMOSOME RATIO. Impact of androgen- and dioxin-related effects in vivo and in vitro.

Abstract

Bibliographical note

Subject classification (UKÄ)

Free keywords

Fingerprint

Cite this