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Androgen receptor gene CAG and GGN repeat lengths as predictors of recovery of spermatogenesis following testicular germ cell cancer treatment

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Asian Journal of Andrology 2017年第5期19卷 538-542页

作者： Karolina Bogefors yvonne lundberg giwercman Jakob Eberhard Olof Stahl Eva Cavallin-Stahl Gabriella Cohn-Cedermark Stefan Arver Aleksander giwercman Reproductive Medicine Centre Skane University Hospital Malmo Sweden Department of Oncology Skane University Hospital Malmo Sweden Department of Translational Medicine Lund University Malmo Sweden Department of Oncology Skane University Hospital Lund Sweden Radiumhemmet Karolinska HospitalStockholm Sweden Centre of Andrology and Sexual Medicine Karolinska Hospital Stockholm Sweden

Spermatogenesis is an androgen-regulated process that depends on the action of androgen receptor （AR）. Sperm production may be affected in men treated for testicular cancer （TC）, and it is important to identify the factors influencing the timing of spermatogenesis recovery following cancer treatment. It is known that the CAG and GGN repeat numbers affect the activity of the AR; therefore, the aim of this study is to investigate if the CAG and GGN polymorphisms in the AR gene predict recovery of sperm production after TC treatment. TC patients （n = 130） delivered ejaculates at the following time points： postorchiectomy and at 6, 12, 24, 36, and 60 months posttherapy （TO, T6, T12, T24, T36, and T60）. The CAG lengths were categorized into three groups, 〈22 CAG, 22-23 CAG, and 〉23 CAG, and the GGN tracts were also categorized into three groups, 〈23 GGN, 23 GGN, and 〉23 GGN. At T12, men with 22-23 CAG presented with a statistically significantly （P = 0.045） lower sperm concentration than those with other CAG numbers （8.4 × 10^6 ml^-1 vs 16 × 10^6 ml^-1; 95% CI： 1.01-2.65）. This association was robust to omitting adjustment for treatment type and sperm concentration at TO （P= 0.021; 3.7× 10^6 ml^-1 vs 10 × 10^6 ml^-1; 95% CI： 1.13-4.90）. The same trends were observed for total sperm number. The least active AR variant seems to be associated with a more rapid recovery of spermatogenesis. This finding adds to our understanding of the biology of postcancer therapy recovery of fertility in males and has clinical implications.

关键词： androgen receptor CAG and GGN repeat sperm number testicular cancer

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Gene-environment interactions in male reproductive health： special reference to the aryl hydrocarbon receptor signaling pathway

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Asian Journal of Andrology 2014年第1期16卷 89-96页

作者： Leon J S Brokken yvonne lundberg giwercman Department of Clinical Sciences Molecular Genetic Reproductive Medicine Lund University MalmO Sweden

Over the last few decades, there have been numerous reports of adverse effects on the reproductive health of wildlife and laboratory animals caused by exposure to endocrine disrupting chemicals （EDCs）. The increasing trends in human male reproductive disorders and the mounting evidence for causative environmental factors have therefore sparked growing interest in the health threat posed to humans by EDCs, which are substances in our food, environment and consumer items that interfere with hormone action, biosynthesis or metabolism, resulting in disrupted tissue homeostasis or reproductive function. The mechanisms of EDCs involve a wide array of actions and pathways. Examples include the estrogenic, androgenic, thyroid and retinoid pathways, in which the EDCs may act directly as agonists or antagonists, or indirectly via other nuclear receptors. Dioxins and dioxin-like EDCs exert their biological and toxicological actions through activation of the aryl hydrocarbon-receptor, which besides inducing transcription of detoxifying enzymes also regulates transcriptional activity of other nuclear receptors. There is increasing evidence that genetic predispositions may modify the susceptibility to adverse effects of toxic chemicals. In this review, potential consequences of hereditary predisposition and EDCs are discussed, with a special focus on the currently available publications on interactions between dioxin and androgen signaling.

关键词： androgen receptor aryl hydrocarbon receptor endocrine disrupter

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通过辅助生殖生育的男性罹患前列腺癌的风险:全国人口登记研究

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英国医学杂志中文版 2022年第7期25卷 375-375页

作者： Yahia AI-Jebari Angel Elenkov Elin Wirestrand Indra Schütz Aleksander Giwereman yvonne lundberg giwercman 董强(译) 李宏军(校) Department of Translational Medicine Lund UniversityMalmöSweden Department of Urology Medical University SofiaSofiaBulgaria Reproductive Medicine Center Skane University Hospital MalmoMalmöSweden 四川大学华西医院泌尿外科中国医学科学院北京协和医院泌尿外科

摘要目的比较通过辅助生殖生育的男性和可让女性自然受孕的男性罹患前列腺癌的风险和严重程度。设计基于国家登记的队列研究。研究地点1994年1月到2014年12月,瑞典。参与者1994-2014年,瑞典有1181490名出生儿童及相同数量的父亲。根据... 详细信息

摘要目的比较通过辅助生殖生育的男性和可让女性自然受孕的男性罹患前列腺癌的风险和严重程度。设计基于国家登记的队列研究。研究地点1994年1月到2014年12月,瑞典。参与者1994-2014年,瑞典有1181490名出生儿童及相同数量的父亲。根据受孕方式进行分组:体外受精(In Vitro Fertilization,IVF)组20618例,胞质内单精子注射(Intracytoplasmic Spermn Injection,ICSI)组14882例,自然受孕组1145990例。

关键词：前列腺癌自然受孕人口登记队列研究生殖生育体外受精胞质内单精子注射

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