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Article ; Online: Sperm counts, testicular cancers, and the environment.

Skakkebaek, Niels E

2017 Volume 359, Page(s) j4517

MeSH term(s)	Humans ; Male ; Regression Analysis ; Sperm Count ; Spermatozoa ; Testicular Neoplasms ; Testis
Language	English
Publishing date	2017-10-10
Publishing country	England
Document type	Editorial ; Comment
ZDB-ID	1362901-3
ISSN	1756-1833 ; 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
ISSN (online)	1756-1833
ISSN	0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
DOI	10.1136/bmj.j4517
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A Brief Review of the Link between Environment and Male Reproductive Health: Lessons from Studies of Testicular Germ Cell Cancer.

Skakkebaek, Niels E

Hormone research in paediatrics

2016 Volume 86, Issue 4, Page(s) 240–246

Abstract: During the past few decades there has been a significantly increasing trend in germ cell tumours all over the world, particularly in countries with Caucasian populations. The changes in incidence have occurred so fast that only environmental factors can ... ...

Abstract	During the past few decades there has been a significantly increasing trend in germ cell tumours all over the world, particularly in countries with Caucasian populations. The changes in incidence have occurred so fast that only environmental factors can explain this development. This review focuses on the hypothesis that testicular germ cell cancer, which originates from germ cell neoplasia in situ, is of foetal origin and associated with other male reproductive problems through a testicular dysgenesis syndrome, also including foetal origin of impaired spermatogenesis, hypospadias and cryptorchidism. There is little doubt that environmental factors associated with modern lifestyles have - in a broad sense - had an adverse influence on male reproductive health. The hypothesis that exposure to endocrine-disrupting chemicals plays a fundamental role in this trend is plausible. This is based on evidence from animal studies that demonstrate adverse reproductive effects caused by a number of endocrine-disrupting chemicals to which humans are exposed as part of our modern lifestyle.
Language	English
Publishing date	2016
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2537278-6
ISSN	1663-2826 ; 1663-2818
ISSN (online)	1663-2826
ISSN	1663-2818
DOI	10.1159/000443400
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Book ; Conference proceedings: International Workshop on the Impact of the Environment on Reproductive Health

Skakkebaek, Niels E.

30 September - 4 October 1991, Copenhagen, Denmark

(Environmental health perspectives ; 101, Suppl. 2 ; NIH publication ; 93-218)

1993

Title variant	Impact of the environment on reproductive health
Event/congress	International Workshop on the Impact of the Environment on Reproductive Health (1991, Kopenhagen)
Author's details	ed. by: Niels E. Skakkebaek
Series title	Environmental health perspectives ; 101, Suppl. 2 NIH publication ; 93-218
Collection
Keywords	Environmental Pollutants / adverse effects / congresses ; Environmental Pollution / congresses ; Reproduction / drug effects / congresses ; Reproduction / congresses ; Risk Factors / congresses
Language	English
Size	482 S. : Ill. graph. Darst.
Publishing place	Research Triangle Park, NC
Publishing country	United States
Document type	Book ; Conference proceedings
HBZ-ID	HT006223541
Database	Catalogue ZB MED Medicine, Health

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Zs B 1360 -101,Suppl.2-	verfügbar in Königswinter	Königswinter

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Book ; Conference proceedings: Management and biology of carcinoma in situ and cancer of the testis

Skakkebaek, Niels E.

proceedings of the 3rd Copenhagen Workshop [on Carcinoma in Situ and Cancer of the Testis], November 1 - 4, 1992

(European urology ; 23,1)

1993

Event/congress	Copenhagen Workshop on Carcinoma in Situ and Cancer of the Testis (3, 1992)
Author's details	guest eds.: Niels E. Skakkebaek
Series title	European urology ; 23,1
Keywords	Testicular Neoplasms / therapy / congresses ; Carcinoma In Situ / congresses
Language	English
Size	IV S., S. [1] - 256 : Ill., graph. Darst.
Publisher	Karger
Publishing place	Basel u.a.
Publishing country	Switzerland
Document type	Book ; Conference proceedings
HBZ-ID	HT004509932
Database	Catalogue ZB MED Medicine, Health

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Zs A 1247 -23-	verfügbar in Königswinter	Königswinter

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Article ; Online: Why Do Normal Children Have Acromegalic Levels of IGF-I During Puberty?

Juul, Anders / Skakkebæk, Niels E

The Journal of clinical endocrinology and metabolism

2019 Volume 104, Issue 7, Page(s) 2770–2776

Abstract: Context: The rapid pubertal height growth is unique to humans, but why do we have it? Although the spurt contributes 13% to 15% to the final adult height, we hypothesized that the biological significance of the high acromegalic levels of GH and IGF-I, ... ...

Abstract	Context: The rapid pubertal height growth is unique to humans, but why do we have it? Although the spurt contributes 13% to 15% to the final adult height, we hypothesized that the biological significance of the high acromegalic levels of GH and IGF-I, which are behind the pubertal growth spurt, might primarily occur to stimulate the reproductive organs. Evidence synthesis: Animal data have demonstrated that adult Igf1 and Igf2 gene knockout mice that survive show a dramatic reduction in the size of the reproductive organs and are infertile. In humans, case reports of mutations in the genes affecting the GH-IGF axis and growth (GH, GHRH, GH-R, STAT5b, IGF-I, IGF-II, IGF-1R, PAPPA2) are also characterized by delayed pubertal onset and micropenis. Furthermore, GH treatment will tend to normalize the penile size in patients with GH deficiency. Thus, the endocrine effects of high IGF-I levels might be needed for the transition of the sexual organs, including the secondary sex characteristics, from the "dormant" stages of childhood into fully functioning reproductive systems. The peak IGF-I levels, on average, occur 2 years after the peak height growth velocity, suggesting reasons other than longitudinal growth for the high IGF-I levels, and remain high in the years after the height spurt, when the reproductive systems become fully functional. Conclusion: We suggest that the serum levels of IGF-I should be monitored in children with poor development of sexual organs, although it remains to be investigated whether GH should be added to sex steroids in the management of hypogonadism for some pubertal children (e.g., boys with micropenis).
MeSH term(s)	Acromegaly/metabolism ; Adolescent ; Adult ; Child ; Child Development ; Fetal Development ; Genitalia/growth & development ; Gonadotropin-Releasing Hormone/metabolism ; Growth ; Human Growth Hormone/metabolism ; Human Growth Hormone/therapeutic use ; Humans ; Hypogonadism/drug therapy ; Insulin-Like Growth Factor Binding Proteins/metabolism ; Insulin-Like Growth Factor I/metabolism ; Insulin-Like Growth Factor II/metabolism ; Puberty/metabolism ; Young Adult
Chemical Substances	Insulin-Like Growth Factor Binding Proteins ; Human Growth Hormone (12629-01-5) ; Gonadotropin-Releasing Hormone (33515-09-2) ; Insulin-Like Growth Factor I (67763-96-6) ; Insulin-Like Growth Factor II (67763-97-7)
Language	English
Publishing date	2019-03-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/jc.2018-02099
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: The epidemiology of cryptorchidism and potential risk factors, including endocrine disrupting chemicals.

Holmboe, Stine A / Beck, Astrid L / Andersson, Anna-Maria / Main, Katharina M / Jørgensen, Niels / Skakkebæk, Niels E / Priskorn, Lærke

Frontiers in endocrinology

2024 Volume 15, Page(s) 1343887

Abstract: Congenital cryptorchidism, also known as undescended testis, is the condition where one or both testes are not in place in the scrotum at birth and is one of the most common birth defects in boys. Temporal trends and geographic variation in the ... ...

Abstract	Congenital cryptorchidism, also known as undescended testis, is the condition where one or both testes are not in place in the scrotum at birth and is one of the most common birth defects in boys. Temporal trends and geographic variation in the prevalence of cryptorchidism from 1% to 9% have been reported in prospective cohort studies. The testes develop in the abdominal cavity and descend to the scrotum in two phases, which should be completed by gestational week 35. Thus, the risk of cryptorchidism is higher in preterm boys. In many cases a spontaneous descent occurs during the first months of life during the surge of gonadotropins and testosterone. If not, the testis is usually brought down to the scrotum, typically by surgery, to increase future fertility chances and facilitate cancer surveillance. The increasing frequency of impaired semen quality and testicular cancer, with which cryptorchidism is associated, represents a concern for male reproductive health in general and a need to understand its risk factors. The risk of cryptorchidism is closely related to gestational factors (preterm birth, low birth weight and intrauterine growth restriction), and especially maternal smoking seems to be a risk factor. Evidence is accumulating that the increasing prevalence of cryptorchidism is also related to prenatal exposure to environmental chemicals, including endocrine disrupting compounds. This association has been corroborated in rodents and supported by ecological studies. Conducting human studies to assess the effect of endocrine disrupting chemicals and their interactions is, however, challenged by the widespread concomitant exposure of all humans to a wide range of chemicals, the combined effect of which and their interactions are highly complex.
MeSH term(s)	Pregnancy ; Female ; Humans ; Male ; Infant, Newborn ; Cryptorchidism/epidemiology ; Testicular Neoplasms/complications ; Endocrine Disruptors ; Prospective Studies ; Semen Analysis ; Premature Birth ; Risk Factors
Chemical Substances	Endocrine Disruptors
Language	English
Publishing date	2024-04-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2024.1343887
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Article ; Online: In vitro investigation of endocrine disrupting effects of pesticides on Ca2+-signaling in human sperm cells through actions on the sperm-specific and steroid-activated CatSper Ca2+-channel

Birch, Michala R. / Johansen, Mathias / Skakkebaek, Niels E. / Andersson, Anna-Maria / Rehfeld, Anders

Environment International. 2022 Sept., v. 167 p.107399-

2022

Abstract: Ca²⁺-signaling controls sperm cell functions necessary for successful fertilization. Multiple endocrine disrupting chemicals have been found to interfere with normal Ca²⁺-signaling in human sperm cells through an activation of the sperm-specific CatSper ... ...

Abstract	Ca²⁺-signaling controls sperm cell functions necessary for successful fertilization. Multiple endocrine disrupting chemicals have been found to interfere with normal Ca²⁺-signaling in human sperm cells through an activation of the sperm-specific CatSper Ca²⁺-channel, which is vital for normal male fertility. We investigated 53 pesticides for their ability to interfere with CatSper mediated Ca²⁺-signaling and function in human sperm cells. Effects of the pesticides on Ca²⁺-signaling in human sperm cells were evaluated using a Ca²⁺-fluorometric assay. Effects via CatSper were assessed using the specific CatSper inhibitor RU1968. Effects on human sperm function and viability were assessed using an image cytometry-based acrosome reaction assay and the modified Kremer's sperm-mucus penetration assay. 28 of 53 pesticides were found to induce Ca²⁺-signals in human sperm cells at 10 µM. The majority of these 28 active pesticides induced Ca²⁺-signals through CatSper and interfered with subsequent Ca²⁺-signals induced by the two endogenous CatSper ligands progesterone and prostaglandin E₁. Multiple active pesticides were found to affect Ca²⁺-mediated sperm functions and viability at 10 µM. Low nM dose mixtures of the active pesticides alone or in combination with other environmental chemicals were found to significantly induce Ca²⁺-signals and inhibit Ca²⁺-signals induced subsequently by progesterone and prostaglandin E₁. Our results show that pesticides, both alone and in low nM dose mixtures, interfere with normal Ca²⁺-signaling in human sperm cells in vitro in low nM concentrations. Biomonitoring of the active pesticides in relevant matrices such as blood and reproductive fluids is very limited and the effects of real time human pesticide exposure on human sperm cells and fertility thus remains largely unknown. To which extent human pesticide exposure affects the chances of a successful fertilization in humans in vivo needs further research.
Keywords	acrosome reaction ; blood ; environment ; environmental monitoring ; humans ; ligands ; male fertility ; pesticides ; progesterone ; prostaglandins ; spermatozoa ; viability ; Endocrine disruption ; Fertility ; CatSper ; Male reproduction
Language	English
Dates of publication	2022-09
Publishing place	Elsevier Ltd
Document type	Article ; Online
Note	Use and reproduction
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2022.107399
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Finasteride interferes with prostaglandin-induced CatSper signalling in human sperm.

Birch, Michala Rosa / Dissing, Steen / Skakkebæk, Niels E / Rehfeld, Anders

Reproduction (Cambridge, England)

2021 Volume 161, Issue 5, Page(s) 561–572

Abstract: Ca2+ signalling controls human sperm functions necessary for successful fertilization. Multiple endocrine-disrupting chemicals have been found to activate the CatSper Ca2+ channel and thereby interfering with Ca2+ signalling in human sperm. Finasteride ... ...

Abstract	Ca2+ signalling controls human sperm functions necessary for successful fertilization. Multiple endocrine-disrupting chemicals have been found to activate the CatSper Ca2+ channel and thereby interfering with Ca2+ signalling in human sperm. Finasteride is prescribed to men in the fertile age to treat hair loss and its use has been associated with impaired male fertility. Due to the structural relatedness of finasteride to the endogenous CatSper ligand progesterone, this study aimed to investigate whether finasteride affects human sperm in a progestogen-like manner. The effect of finasteride on Ca2+ signalling via CatSper in human sperm was investigated in cell suspensions by single-cell imaging. Additionally, effects on sperm penetration into viscous medium and acrosome reaction were assessed. Finasteride alone caused a minor transient rise in the intracellular, free Ca2+ concentration ([Ca2+]i) at physiologically relevant concentrations. Ca2+ signals induced by PGE1 were inhibited by finasteride displaying mixed type of inhibition consistent with multiple binding sites. Finasteride did not interfere with progesterone-induced Ca2+ signalling and no effect on acrosome reaction or sperm viability was found. Finasteride significantly decreased PGE1-induced penetration into viscous medium but in concentrations above what is measured in blood and seminal fluids during regular finasteride administration. In conclusion, the use of finasteride may affect Ca2+ signalling in human sperm through an interaction with the PGE1-binding site, but to which extend it alters the chances of a successful fertilization needs further investigation. It remains to be investigated whether finasteride administration may give rise to side effects by interfering with prostaglandin signalling elsewhere in the human body.
MeSH term(s)	5-alpha Reductase Inhibitors/pharmacology ; Calcium/metabolism ; Calcium Channels/genetics ; Calcium Channels/metabolism ; Calcium Signaling ; Finasteride/pharmacology ; Gene Expression Regulation/drug effects ; Humans ; Male ; Prostaglandins/pharmacology ; Sperm Motility/drug effects ; Spermatozoa/drug effects ; Spermatozoa/metabolism
Chemical Substances	5-alpha Reductase Inhibitors ; CATSPER1 protein, human ; Calcium Channels ; Prostaglandins ; Finasteride (57GNO57U7G) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2021-04-06
Publishing country	England
Document type	Journal Article
ZDB-ID	2034501-X
ISSN	1741-7899 ; 1470-1626 ; 1476-3990
ISSN (online)	1741-7899
ISSN	1470-1626 ; 1476-3990
DOI	10.1530/REP-20-0287
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Article ; Online: In vitro investigation of endocrine disrupting effects of pesticides on Ca

Birch, Michala R / Johansen, Mathias / Skakkebæk, Niels E / Andersson, Anna-Maria / Rehfeld, Anders

Environment international

2022 Volume 167, Page(s) 107399

Abstract: Background: Ca: Objectives: We investigated 53 pesticides for their ability to interfere with CatSper mediated Ca: Methods: Effects of the pesticides on Ca: Results: 28 of 53 pesticides were found to induce Ca: Conclusions: Our results show ... ...

Abstract	Background: Ca Objectives: We investigated 53 pesticides for their ability to interfere with CatSper mediated Ca Methods: Effects of the pesticides on Ca Results: 28 of 53 pesticides were found to induce Ca Conclusions: Our results show that pesticides, both alone and in low nM dose mixtures, interfere with normal Ca
MeSH term(s)	Calcium ; Calcium Channels/metabolism ; Calcium Signaling ; Humans ; Male ; Pesticides/metabolism ; Progesterone ; Prostaglandins/metabolism ; Prostaglandins/pharmacology ; Semen/metabolism ; Sperm Motility ; Spermatozoa
Chemical Substances	Calcium Channels ; Pesticides ; Prostaglandins ; Progesterone (4G7DS2Q64Y) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2022-07-09
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2022.107399
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Article: A Brief Review of the Link between Environment and Male Reproductive Health: Lessons from Studies of Testicular Germ Cell Cancer

Skakkebaek, Niels E.

Hormone Research in Paediatrics

2016 Volume 86, Issue 4, Page(s) 240–246

Institution	University Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark
Abstract	During the past few decades there has been a significantly increasing trend in germ cell tumours all over the world, particularly in countries with Caucasian populations. The changes in incidence have occurred so fast that only environmental factors can explain this development. This review focuses on the hypothesis that testicular germ cell cancer, which originates from germ cell neoplasia in situ, is of foetal origin and associated with other male reproductive problems through a testicular dysgenesis syndrome, also including foetal origin of impaired spermatogenesis, hypospadias and cryptorchidism. There is little doubt that environmental factors associated with modern lifestyles have - in a broad sense - had an adverse influence on male reproductive health. The hypothesis that exposure to endocrine-disrupting chemicals plays a fundamental role in this trend is plausible. This is based on evidence from animal studies that demonstrate adverse reproductive effects caused by a number of endocrine-disrupting chemicals to which humans are exposed as part of our modern lifestyle.
Keywords	Testicular cancer ; Testicular dysgenesis syndrome ; Endocrine disrupters ; Reproduction ; Hypospadias ; Cryptorchidism
Language	English
Publishing date	2016-02-13
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Mini Review
ZDB-ID	2537278-6
ISBN	978-3-318-05971-7 ; 978-3-318-05972-4 ; 3-318-05971-4 ; 3-318-05972-2
ISSN	1663-2826 ; 1663-2818
ISSN (online)	1663-2826
ISSN	1663-2818
DOI	10.1159/000443400
Database	Karger publisher's database

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