Abstract:
BACKGROUND:Overall, the incidence of male reproductive disorders has increased in recent decades. Testicular development during fetal life is crucial for subsequent male reproductive function. Non-genomic factors such as environmental chemicals, pharmaceuticals and lifestyle have been proposed to impact on human fetal testicular development resulting in subsequent effects on male reproductive health. Whilst experimental studies using animal models have provided support for this hypothesis, more recently a number of experimental studies using human tissues and cells have begun to translate these findings to determine direct human relevance. OBJECTIVE AND RATIONALE:The objective of this systematic review was to provide a comprehensive description of the evidence for effects of prenatal exposure(s) on human fetal testis development and function. We present the effects of environmental, pharmaceutical and lifestyle factors in experimental systems involving exposure of human fetal testis tissues and cells. Comparison is made with existing epidemiological data primarily derived from a recent meta-analysis. SEARCH METHODS:For identification of experimental studies, PubMed and EMBASE were searched for articles published in English between 01/01/1966 and 13/07/2018 using search terms including 'endocrine disruptor', 'human', 'fetal', 'testis', 'germ cells', 'testosterone' and related search terms. Abstracts were screened for selection of full-text articles for further interrogation. Epidemiological studies involving exposure to the same agents were extracted from a recent systematic review and meta-analysis. Additional studies were identified through screening of bibliographies of full-texts of articles identified through the initial searches. OUTCOMES:A total of 25 experimental studies and 44 epidemiological studies were included. Consistent effects of analgesic and phthalate exposure on human fetal germ cell development are demonstrated in experimental models, correlating with evidence from epidemiological studies and animal models. Furthermore, analgesic-induced reduction in fetal testosterone production, which predisposes to the development of male reproductive disorders, has been reported in studies involving human tissues, which also supports data from animal and epidemiological studies. However, whilst reduced testosterone production has been demonstrated in animal studies following exposure(s) to a variety of environmental chemicals including phthalates and bisphenol A, these effects are not reproduced in experimental approaches using human fetal testis tissues. WIDER IMPLICATIONS:Direct experimental evidence for effects of prenatal exposure(s) on human fetal testis development and function exists. However, for many exposures the data is limited. The increasing use of human-relevant models systems in which to determine the effects of environmental exposure(s) (including mixed exposures) on development and function of human tissues should form an important part of the process for assessment of such exposures by regulatory bodies to take account of animal-human differences in susceptibility.
journal_name
Hum Reprod Updatejournal_title
Human reproduction updateauthors
Kilcoyne KR,Mitchell RTdoi
10.1093/humupd/dmz004subject
Has Abstractpub_date
2019-07-01 00:00:00pages
397-421issue
4eissn
1355-4786issn
1460-2369pii
5380620journal_volume
25pub_type
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pub_type: 杂志文章,meta分析,评审
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更新日期:2016-03-01 00:00:00
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
doi:10.1093/humupd/dmy026
更新日期:2018-11-01 00:00:00
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pub_type: 杂志文章,评审
doi:10.1093/humupd/dmr028
更新日期:2011-11-01 00:00:00
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pub_type: 杂志文章,评审
doi:10.1093/humupd/dmh052
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pub_type: 杂志文章,评审
doi:10.1093/humupd/4.5.752
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pub_type: 杂志文章,meta分析,评审
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更新日期:2010-09-01 00:00:00
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pub_type: 历史文章,杂志文章,评审
doi:10.1093/humupd/5.6.565
更新日期:1999-11-01 00:00:00
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pub_type: 杂志文章,评审
doi:10.1093/humupd/4.6.904
更新日期:1998-11-01 00:00:00
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pub_type: 杂志文章,meta分析
doi:10.1093/humupd/dmq031
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pub_type: 社论
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pub_type:
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更新日期:2011-11-01 00:00:00
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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更新日期:2008-03-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2007-05-01 00:00:00
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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更新日期:2003-03-01 00:00:00