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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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/8/6914 |
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| author | Xingfa Han Xue Xia Weihao Chen Fengyan Meng Xiaohan Cao Guixian Bu Tian Gan Xiaogang Du Qiuxia Liang Xianyin Zeng |
| author_facet | Xingfa Han Xue Xia Weihao Chen Fengyan Meng Xiaohan Cao Guixian Bu Tian Gan Xiaogang Du Qiuxia Liang Xianyin Zeng |
| author_sort | Xingfa Han |
| collection | DOAJ |
| 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 (<i>p</i> < 0.05) antibody generation, enhanced (<i>p</i> < 0.05) ovarian follicle development, and increased ovulation rate and litter sizes. Mechanistically, INHα13AA-T immunization promoted (<i>p</i> < 0.05) pituitary <i>Fshb</i> transcription and increased (<i>p</i> < 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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| last_indexed | 2024-03-11T04:57:59Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4c8f9df831e54bdea912046d102671cb2023-11-17T19:32:21ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248691410.3390/ijms24086914Efficacy of Immunization against a Novel Synthetic 13-Amino Acid Betaglycan-Binding Peptide Sequence of Inhibin α Subunit on Promoting Fertility in Female RatsXingfa Han0Xue Xia1Weihao Chen2Fengyan Meng3Xiaohan Cao4Guixian Bu5Tian Gan6Xiaogang Du7Qiuxia Liang8Xianyin Zeng9Isotope Research Lab, College of Life Science, Sichuan Agricultural University, Ya’an 625014, ChinaIsotope Research Lab, College of Life Science, Sichuan Agricultural University, Ya’an 625014, ChinaIsotope Research Lab, College of Life Science, Sichuan Agricultural University, Ya’an 625014, ChinaIsotope Research Lab, College of Life Science, Sichuan Agricultural University, Ya’an 625014, ChinaIsotope Research Lab, College of Life Science, Sichuan Agricultural University, Ya’an 625014, ChinaIsotope Research Lab, College of Life Science, Sichuan Agricultural University, Ya’an 625014, ChinaIsotope Research Lab, College of Life Science, Sichuan Agricultural University, Ya’an 625014, ChinaIsotope Research Lab, College of Life Science, Sichuan Agricultural University, Ya’an 625014, ChinaIsotope Research Lab, College of Life Science, Sichuan Agricultural University, Ya’an 625014, ChinaIsotope Research Lab, College of Life Science, Sichuan Agricultural University, Ya’an 625014, ChinaInhibins 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 (<i>p</i> < 0.05) antibody generation, enhanced (<i>p</i> < 0.05) ovarian follicle development, and increased ovulation rate and litter sizes. Mechanistically, INHα13AA-T immunization promoted (<i>p</i> < 0.05) pituitary <i>Fshb</i> transcription and increased (<i>p</i> < 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.https://www.mdpi.com/1422-0067/24/8/6914inhibinvaccinefolliculogenesisovulationfertilityrat |
| spellingShingle | Xingfa Han Xue Xia Weihao Chen Fengyan Meng Xiaohan Cao Guixian Bu Tian Gan Xiaogang Du Qiuxia Liang Xianyin Zeng Efficacy of Immunization against a Novel Synthetic 13-Amino Acid Betaglycan-Binding Peptide Sequence of Inhibin α Subunit on Promoting Fertility in Female Rats International Journal of Molecular Sciences inhibin vaccine folliculogenesis ovulation fertility rat |
| 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 | inhibin vaccine folliculogenesis ovulation fertility rat |
| url | https://www.mdpi.com/1422-0067/24/8/6914 |
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