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Efficacy of Immunization against a Novel Synthetic 13-Amino Acid Betaglycan-Binding Peptide Sequence of Inhibin α Subunit on Promoting Fertility in Female Rats

Inhibins suppress the FSH production in pituitary gonadotrope cells by robustly antagonizing activin signaling by competitively binding to activin type II receptors (ACTR II). The binding of inhibin A to ACTR II requires the presence of its co-receptor, namely, betaglycan. In humans, the critical bi...

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Autores principales: Han, Xingfa, Xia, Xue, Chen, Weihao, Meng, Fengyan, Cao, Xiaohan, Bu, Guixian, Gan, Tian, Du, Xiaogang, Liang, Qiuxia, Zeng, Xianyin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138769/
https://www.ncbi.nlm.nih.gov/pubmed/37108077
http://dx.doi.org/10.3390/ijms24086914
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author Han, Xingfa
Xia, Xue
Chen, Weihao
Meng, Fengyan
Cao, Xiaohan
Bu, Guixian
Gan, Tian
Du, Xiaogang
Liang, Qiuxia
Zeng, Xianyin
author_facet Han, Xingfa
Xia, Xue
Chen, Weihao
Meng, Fengyan
Cao, Xiaohan
Bu, Guixian
Gan, Tian
Du, Xiaogang
Liang, Qiuxia
Zeng, Xianyin
author_sort Han, Xingfa
collection PubMed
description Inhibins suppress the FSH production in pituitary gonadotrope cells by robustly antagonizing activin signaling by competitively binding to activin type II receptors (ACTR II). The binding of inhibin A to ACTR II requires the presence of its co-receptor, namely, betaglycan. In humans, the critical binding site for betaglycan to inhibin A was identified on the inhibin α subunit. Through conservation analysis, we found that a core 13-amino-acid peptide sequence <VRTTSDGGYSFKY> within the betaglycan-binding epitope on human inhibin α subunit is highly conserved across species. Based on the tandem sequence of such a conserved 13-amino-acid betaglycan-binding epitope (INHα13AA-T), we developed a novel inhibin vaccine and tested its efficacy in promoting female fertility using the female rat as a model. Compared with placebo-immunized controls, INHα13AA-T immunization induced a marked (p < 0.05) antibody generation, enhanced (p < 0.05) ovarian follicle development, and increased ovulation rate and litter sizes. Mechanistically, INHα13AA-T immunization promoted (p < 0.05) pituitary Fshb transcription and increased (p < 0.05) serum FSH and 17β-estradiol concentrations. In summary, active immunization against INHα13AA-T potently increased FSH levels, ovarian follicle development, ovulation rate and litter sizes, thus causing super-fertility in females. Therefore, immunization against INHα13AA is a promising alternative to the conventional approach of multiple ovulation and super-fertility in mammals.
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spelling pubmed-101387692023-04-28 Efficacy of Immunization against a Novel Synthetic 13-Amino Acid Betaglycan-Binding Peptide Sequence of Inhibin α Subunit on Promoting Fertility in Female Rats Han, Xingfa Xia, Xue Chen, Weihao Meng, Fengyan Cao, Xiaohan Bu, Guixian Gan, Tian Du, Xiaogang Liang, Qiuxia Zeng, Xianyin Int J Mol Sci Article Inhibins suppress the FSH production in pituitary gonadotrope cells by robustly antagonizing activin signaling by competitively binding to activin type II receptors (ACTR II). The binding of inhibin A to ACTR II requires the presence of its co-receptor, namely, betaglycan. In humans, the critical binding site for betaglycan to inhibin A was identified on the inhibin α subunit. Through conservation analysis, we found that a core 13-amino-acid peptide sequence <VRTTSDGGYSFKY> within the betaglycan-binding epitope on human inhibin α subunit is highly conserved across species. Based on the tandem sequence of such a conserved 13-amino-acid betaglycan-binding epitope (INHα13AA-T), we developed a novel inhibin vaccine and tested its efficacy in promoting female fertility using the female rat as a model. Compared with placebo-immunized controls, INHα13AA-T immunization induced a marked (p < 0.05) antibody generation, enhanced (p < 0.05) ovarian follicle development, and increased ovulation rate and litter sizes. Mechanistically, INHα13AA-T immunization promoted (p < 0.05) pituitary Fshb transcription and increased (p < 0.05) serum FSH and 17β-estradiol concentrations. In summary, active immunization against INHα13AA-T potently increased FSH levels, ovarian follicle development, ovulation rate and litter sizes, thus causing super-fertility in females. Therefore, immunization against INHα13AA is a promising alternative to the conventional approach of multiple ovulation and super-fertility in mammals. MDPI 2023-04-07 /pmc/articles/PMC10138769/ /pubmed/37108077 http://dx.doi.org/10.3390/ijms24086914 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Han, Xingfa
Xia, Xue
Chen, Weihao
Meng, Fengyan
Cao, Xiaohan
Bu, Guixian
Gan, Tian
Du, Xiaogang
Liang, Qiuxia
Zeng, Xianyin
Efficacy of Immunization against a Novel Synthetic 13-Amino Acid Betaglycan-Binding Peptide Sequence of Inhibin α Subunit on Promoting Fertility in Female Rats
title Efficacy of Immunization against a Novel Synthetic 13-Amino Acid Betaglycan-Binding Peptide Sequence of Inhibin α Subunit on Promoting Fertility in Female Rats
title_full Efficacy of Immunization against a Novel Synthetic 13-Amino Acid Betaglycan-Binding Peptide Sequence of Inhibin α Subunit on Promoting Fertility in Female Rats
title_fullStr Efficacy of Immunization against a Novel Synthetic 13-Amino Acid Betaglycan-Binding Peptide Sequence of Inhibin α Subunit on Promoting Fertility in Female Rats
title_full_unstemmed Efficacy of Immunization against a Novel Synthetic 13-Amino Acid Betaglycan-Binding Peptide Sequence of Inhibin α Subunit on Promoting Fertility in Female Rats
title_short Efficacy of Immunization against a Novel Synthetic 13-Amino Acid Betaglycan-Binding Peptide Sequence of Inhibin α Subunit on Promoting Fertility in Female Rats
title_sort efficacy of immunization against a novel synthetic 13-amino acid betaglycan-binding peptide sequence of inhibin α subunit on promoting fertility in female rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138769/
https://www.ncbi.nlm.nih.gov/pubmed/37108077
http://dx.doi.org/10.3390/ijms24086914
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