ENVIRONMENTAL CONTAMINANTS AND SPERM Y:X CHROMOSOME RATIO. Impact of androgen- and dioxin-related effects in vivo and in vitro.
Author
Summary, in English
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.
Department/s
Publishing year
2007
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2007:73
Document type
Dissertation
Publisher
Department of Clinical Sciences, Lund University
Topic
- Obstetrics, Gynecology and Reproductive Medicine
Keywords
- AR
- polymorphisms
- Sertoli cell
- endocrine disruption
- inhibitory cross-talk
- Biomedicinska vetenskaper
- Biomedical sciences
- AHR
- sperm Y:X chromosome ratio
- sex ratio
- POPs
- TCDD
Status
Published
Research group
- Reproductive medicine, Malmö
Supervisor
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-85559-51-0
Defence date
16 May 2007
Defence time
09:00
Defence place
CRC Aula, Clinical Research Centre, Malmö University Hospital, entrance 72
Opponent
- Jorma Toppari (Professor)