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Research
Suyun Zhang
Nanjing Medical University affiliated Nanjing Hospital: Nanjing First Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0003-3445-0088
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Perfluorohexane sulfonate (PFHxS) is a six-carbon perfluoroalkyl sulfonic acid found as an environmental contaminant. This study aims to investigate the effects of PFHxS exposure on female reproduction and the underlying mechanism in mice.
Methods
Eight-week-old ICR mice were divided randomly into four groups: corn oil (vehicle) and PFHxS at doses of 0.5, 5, and 50 mg/kg/day for 42 days by intragastric administration. Body weight, ovarian weight, estrous cycle, follicle counts, and serum sex hormone levels were evaluated. Expression of kisspeptin and gonadotropin releasing hormone (GnRH) in the hypothalamus was also detected.
Results
Compared to vehicle exposure, 5 mg/kg/day PFHxS prolonged the estrous cycle, especially the duration of diestrus, after 42 days of treatment. The numbers of antral follicles and corpus lutea were significantly reduced in PFHxS-treated mice. Moreover, compared with the control group, PFHxS-treated mice showed decreases in serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estrogen (E2), and reduced GnRH mRNA levels, along with the lack of an LH surge. Furthermore, PFHxS-treated mice had lower levels of kisspeptin immunoreactivity and kiss-1 mRNA in the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV). After intraventricular administration of kisspeptin-10, the numbers of antral follicles and corpus lutea recovered, along with the levels of GnRH mRNA, FSH, and LH in mice treated with 5 mg/kg/day PFHxS.
Conclusion
These results indicate that chronic exposure of mice to 5 mg/kg/day PFHxS affects reproductive functions by inhibiting kisspeptin expression in the ARC and AVPV regions, leading to the deficit of follicular development and ovulation.
Keywords
perfluorohexane sulfonate, kisspeptin, reproduction, hypothalamus
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CURRENT STATUS: Under Review
Version 1
Posted 09 Jun, 2021
No community comments so far
Editorial decision: Major revision
On 03 Aug, 2021
Review #2 received
Received 19 Jul, 2021
Review #1 received
Received 11 Jul, 2021
Reviewer #2 agreed
On 08 Jul, 2021
Reviews received
Received 08 Jul, 2021
Reviewers invited
Invitations sent on 08 Jul, 2021
Reviewer #1 agreed
On 07 Jul, 2021
Editor assigned
On 30 May, 2021
Submission checks complete
On 30 May, 2021
Editor invited
On 30 May, 2021
First submitted
On 28 May, 2021
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This preprint is under consideration at Journal of Ovarian Research. 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
Suyun Zhang
Nanjing Medical University affiliated Nanjing Hospital: Nanjing First Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0003-3445-0088
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: Under Review
Version 1
Posted 09 Jun, 2021
No community comments so far
Editorial decision: Major revision
On 03 Aug, 2021
Review #2 received
Received 19 Jul, 2021
Review #1 received
Received 11 Jul, 2021
Reviewer #2 agreed
On 08 Jul, 2021
Reviews received
Received 08 Jul, 2021
Reviewers invited
Invitations sent on 08 Jul, 2021
Reviewer #1 agreed
On 07 Jul, 2021
Editor assigned
On 30 May, 2021
Submission checks complete
On 30 May, 2021
Editor invited
On 30 May, 2021
First submitted
On 28 May, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Perfluorohexane sulfonate (PFHxS) is a six-carbon perfluoroalkyl sulfonic acid found as an environmental contaminant. This study aims to investigate the effects of PFHxS exposure on female reproduction and the underlying mechanism in mice.
Methods
Eight-week-old ICR mice were divided randomly into four groups: corn oil (vehicle) and PFHxS at doses of 0.5, 5, and 50 mg/kg/day for 42 days by intragastric administration. Body weight, ovarian weight, estrous cycle, follicle counts, and serum sex hormone levels were evaluated. Expression of kisspeptin and gonadotropin releasing hormone (GnRH) in the hypothalamus was also detected.
Results
Compared to vehicle exposure, 5 mg/kg/day PFHxS prolonged the estrous cycle, especially the duration of diestrus, after 42 days of treatment. The numbers of antral follicles and corpus lutea were significantly reduced in PFHxS-treated mice. Moreover, compared with the control group, PFHxS-treated mice showed decreases in serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estrogen (E2), and reduced GnRH mRNA levels, along with the lack of an LH surge. Furthermore, PFHxS-treated mice had lower levels of kisspeptin immunoreactivity and kiss-1 mRNA in the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV). After intraventricular administration of kisspeptin-10, the numbers of antral follicles and corpus lutea recovered, along with the levels of GnRH mRNA, FSH, and LH in mice treated with 5 mg/kg/day PFHxS.
Conclusion
These results indicate that chronic exposure of mice to 5 mg/kg/day PFHxS affects reproductive functions by inhibiting kisspeptin expression in the ARC and AVPV regions, leading to the deficit of follicular development and ovulation.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
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