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In Utero and Peripubertal Metals Exposure in Relation to Reproductive Hormones and Sexual Maturation and Progression among Boys in Mexico City
Deborah Watkins
University of Michigan School of Public Health
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6692-2206
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Environmental Health.
Background
Endocrine disrupting chemicals (EDCs) such as metals have been reported to alter circulating reproductive hormone concentrations and pubertal development in animals. However, the relationship has rarely been investigated among humans, with the exception of heavy metals, such as Pb and Cd. Our aim was to investigate measures of in utero and peripubertal metal exposure in relation to reproductive hormone levels and sexual maturation and progression among boys from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohorts.
Methods
Our analysis included 118 pregnant women and their male children from the ELEMENT study. Essential and non-essential metals were measured in urine collected from the mothers during the third trimester of pregnancy and their male children at 8-14 years. Reproductive hormone levels serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG) were measured in blood samples from the children at 8-14 years. We also assessed Tanner stages for sexual maturation (genital, pubic hair development, and testicular volume), at two time points (8–14, 10-18 years). We used linear regression to independently examine urinary metal levels in relation to each peripubertal reproductive hormones adjusting for child age and BMI. Generalized estimation equations (GEEs) were used to evaluate the association of in utero and peripubertal metal exposures with sexual maturation and progression during follow-up based on Tanner staging and testicular volume.
Results
In utero and prepubertal concentrations of some urinary metals were associated with increased levels of peripubertal reproductive hormones, especially non-essential metal(loid)s As and Cd ( in utero ), and Ba (peripubertal) as well as essential metal Mo ( in utero ) in association with testosterone. More advanced pubic hair developmental stage and higher testicular volume at the early teen visit was observed for boys with higher non-essential metal concentrations, including in utero Al and peripubertal Ba, and essential metal Zn concentration (peripubertal). These metals were also associated with slower pubertal progression between the two visits.
Conclusion
These findings suggest that male reproductive development may be associated with both essential and non-essential metal exposure during in utero and peripubertal windows.
Keywords
Metal, Hormone, In utero exposure, Pregnancy, Puberty
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CURRENT STATUS: Published
Published
On 25 Nov, 2020
No community comments so far
Editorial decision: Accept
On 29 Oct, 2020
Editor assigned
On 22 Oct, 2020
Submission checks complete
On 21 Oct, 2020
Editor invited
On 21 Oct, 2020
No comments provided
Editorial decision: Accept with minor revisions
On 20 Oct, 2020
Reviewers invited
Invitations sent on 14 Oct, 2020
Reviewer #1 agreed
On 14 Oct, 2020
Review #1 received
Received 14 Oct, 2020
Editor assigned
On 13 Oct, 2020
Submission checks complete
On 12 Oct, 2020
Editor invited
On 12 Oct, 2020
No comments provided
Review #2 received
Received 26 Sep, 2020
Editorial decision: Minor revision
On 26 Sep, 2020
Review #1 received
Received 21 Sep, 2020
Reviewer #2 agreed
On 18 Sep, 2020
Reviewers invited
Invitations sent on 17 Sep, 2020
Reviewer #1 agreed
On 17 Sep, 2020
Editor assigned
On 16 Sep, 2020
Submission checks complete
On 15 Sep, 2020
Editor invited
On 15 Sep, 2020
Version 1
Posted 12 Jun, 2020
No comments provided
Editorial decision: Major revision
On 17 Aug, 2020
Review #2 received
Received 16 Aug, 2020
Reviewer #2 agreed
On 25 Jul, 2020
Review #1 received
Received 07 Jul, 2020
Reviewer #1 agreed
On 19 Jun, 2020
Reviewers invited
Invitations sent on 18 Jun, 2020
Editor assigned
On 11 Jun, 2020
First submitted
On 10 Jun, 2020
Submission checks complete
On 10 Jun, 2020
Editor invited
On 10 Jun, 2020
Metrics
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PDF Downloads: ...
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This preprint is under consideration at Environmental Health. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
In Utero and Peripubertal Metals Exposure in Relation to Reproductive Hormones and Sexual Maturation and Progression among Boys in Mexico City
Deborah Watkins
University of Michigan School of Public Health
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6692-2206
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Published
On 25 Nov, 2020
No community comments so far
Editorial decision: Accept
On 29 Oct, 2020
Editor assigned
On 22 Oct, 2020
Submission checks complete
On 21 Oct, 2020
Editor invited
On 21 Oct, 2020
No comments provided
Editorial decision: Accept with minor revisions
On 20 Oct, 2020
Reviewers invited
Invitations sent on 14 Oct, 2020
Reviewer #1 agreed
On 14 Oct, 2020
Review #1 received
Received 14 Oct, 2020
Editor assigned
On 13 Oct, 2020
Submission checks complete
On 12 Oct, 2020
Editor invited
On 12 Oct, 2020
No comments provided
Review #2 received
Received 26 Sep, 2020
Editorial decision: Minor revision
On 26 Sep, 2020
Review #1 received
Received 21 Sep, 2020
Reviewer #2 agreed
On 18 Sep, 2020
Reviewers invited
Invitations sent on 17 Sep, 2020
Reviewer #1 agreed
On 17 Sep, 2020
Editor assigned
On 16 Sep, 2020
Submission checks complete
On 15 Sep, 2020
Editor invited
On 15 Sep, 2020
Version 1
Posted 12 Jun, 2020
No comments provided
Editorial decision: Major revision
On 17 Aug, 2020
Review #2 received
Received 16 Aug, 2020
Reviewer #2 agreed
On 25 Jul, 2020
Review #1 received
Received 07 Jul, 2020
Reviewer #1 agreed
On 19 Jun, 2020
Reviewers invited
Invitations sent on 18 Jun, 2020
Editor assigned
On 11 Jun, 2020
First submitted
On 10 Jun, 2020
Submission checks complete
On 10 Jun, 2020
Editor invited
On 10 Jun, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Environmental Health.
Background
Endocrine disrupting chemicals (EDCs) such as metals have been reported to alter circulating reproductive hormone concentrations and pubertal development in animals. However, the relationship has rarely been investigated among humans, with the exception of heavy metals, such as Pb and Cd. Our aim was to investigate measures of in utero and peripubertal metal exposure in relation to reproductive hormone levels and sexual maturation and progression among boys from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohorts.
Methods
Our analysis included 118 pregnant women and their male children from the ELEMENT study. Essential and non-essential metals were measured in urine collected from the mothers during the third trimester of pregnancy and their male children at 8-14 years. Reproductive hormone levels serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG) were measured in blood samples from the children at 8-14 years. We also assessed Tanner stages for sexual maturation (genital, pubic hair development, and testicular volume), at two time points (8–14, 10-18 years). We used linear regression to independently examine urinary metal levels in relation to each peripubertal reproductive hormones adjusting for child age and BMI. Generalized estimation equations (GEEs) were used to evaluate the association of in utero and peripubertal metal exposures with sexual maturation and progression during follow-up based on Tanner staging and testicular volume.
Results
In utero and prepubertal concentrations of some urinary metals were associated with increased levels of peripubertal reproductive hormones, especially non-essential metal(loid)s As and Cd ( in utero ), and Ba (peripubertal) as well as essential metal Mo ( in utero ) in association with testosterone. More advanced pubic hair developmental stage and higher testicular volume at the early teen visit was observed for boys with higher non-essential metal concentrations, including in utero Al and peripubertal Ba, and essential metal Zn concentration (peripubertal). These metals were also associated with slower pubertal progression between the two visits.
Conclusion
These findings suggest that male reproductive development may be associated with both essential and non-essential metal exposure during in utero and peripubertal windows.
Figure 1
Figure 2
Figure 3