Development of highly bioactive long-acting recombinant porcine FSH for batch production management of sows

Abstract To improve the economic benefits, exogenous hormones are used to control follicular development and synchronize ovulation in the batch flow management of gilts and weaned sows. Equine chorionic gonadotropin (eCG) is widely used to stimulate follicular development in both experimental and fa...

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Main Authors: Jiawei Zhang, Lei Shi, Xiaorong Zhong, Yunhe Bai, Jun Dou, Lu Zhang, Xiaochao Shi, Bingchun Wu, Zemin Tan, Lin Yan, Jinku Yu, Jingru Zhang, Guo Han, Jiansheng Xiong, Hua Zhang, Xingyuan Cao, Haoshu Luo
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Language:English
Published: Nature Portfolio 2025-02-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-89356-8
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author Jiawei Zhang
Lei Shi
Xiaorong Zhong
Yunhe Bai
Jun Dou
Lu Zhang
Xiaochao Shi
Bingchun Wu
Zemin Tan
Lin Yan
Jinku Yu
Jingru Zhang
Guo Han
Jiansheng Xiong
Hua Zhang
Xingyuan Cao
Haoshu Luo
author_facet Jiawei Zhang
Lei Shi
Xiaorong Zhong
Yunhe Bai
Jun Dou
Lu Zhang
Xiaochao Shi
Bingchun Wu
Zemin Tan
Lin Yan
Jinku Yu
Jingru Zhang
Guo Han
Jiansheng Xiong
Hua Zhang
Xingyuan Cao
Haoshu Luo
author_sort Jiawei Zhang
collection DOAJ
description Abstract To improve the economic benefits, exogenous hormones are used to control follicular development and synchronize ovulation in the batch flow management of gilts and weaned sows. Equine chorionic gonadotropin (eCG) is widely used to stimulate follicular development in both experimental and farm animals. Despite its effectiveness, several side effects have been found, including the occurrence of follicular cysts, follicular premature luteinization, and increased follicular atresia. As eCG is a heterologous protein, the generation of antibodies has been found in the superovulation of cattle. Moreover, the extraction of eCG from pregnant mare serum raises concerns regarding animal welfare, as well as potential risks for disease transmission. Follicle stimulating hormone (FSH) controls the follicular growth and maturation in the porcine ovary under physiological conditions. In the current study, we developed a novel long-acting recombinant porcine FSH (rpFSH-pFc) consisting of porcine FSH and porcine fragment crystallizable (Fc) via (G4S)3 linker by using the available protein fusion technology to control the follicular development and maturation. The results of pharmacokinetic studies indicated that rpFSH-pFc exhibited a prolonged half-life in both rats and sows. The efficacy of rpFSH-pFc was confirmed by cAMP level evaluation and germinal vesicle breakdown (GVBD) analysis in vitro. Through ovarian weight gain, superovulation and fertility testing assays, our results revealed that a single rpFSH-pFc treatment could effectively promote follicular development and maturation in vivo. Meanwhile, the mRNA expression levels of the target genes associated with follicular development, maturation and ovulation were significantly up-regulated after rpFSH-pFc treatment. Taken together, our results revealed that rpFSH-pFc could bind to the FSH receptor, stimulate follicular growth and development in female mice, and possess a prolonged half-life in both rats and sows. These characteristics suggest that rpFSH-pFc may be an ideal candidate for promoting follicular growth and development in livestock production.
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spelling doaj-art-1ad1695fd1b5484bbbae54a80546858b2025-02-09T12:33:02ZengNature PortfolioScientific Reports2045-23222025-02-0115111510.1038/s41598-025-89356-8Development of highly bioactive long-acting recombinant porcine FSH for batch production management of sowsJiawei Zhang0Lei Shi1Xiaorong Zhong2Yunhe Bai3Jun Dou4Lu Zhang5Xiaochao Shi6Bingchun Wu7Zemin Tan8Lin Yan9Jinku Yu10Jingru Zhang11Guo Han12Jiansheng Xiong13Hua Zhang14Xingyuan Cao15Haoshu Luo16Beijing VJTBio Co., LTDBeijing VJTBio Co., LTDBeijing VJTBio Co., LTDBeijing VJTBio Co., LTDBeijing VJTBio Co., LTDDepartment of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural UniversityBeijing VJTBio Co., LTDBeijing VJTBio Co., LTDBeijing VJTBio Co., LTDBeijing VJTBio Co., LTDBeijing VJTBio Co., LTDBeijing VJTBio Co., LTDBeijing VJTBio Co., LTDBeijing VJTBio Co., LTDState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural UniversityDepartment of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural UniversityBeijing VJTBio Co., LTDAbstract To improve the economic benefits, exogenous hormones are used to control follicular development and synchronize ovulation in the batch flow management of gilts and weaned sows. Equine chorionic gonadotropin (eCG) is widely used to stimulate follicular development in both experimental and farm animals. Despite its effectiveness, several side effects have been found, including the occurrence of follicular cysts, follicular premature luteinization, and increased follicular atresia. As eCG is a heterologous protein, the generation of antibodies has been found in the superovulation of cattle. Moreover, the extraction of eCG from pregnant mare serum raises concerns regarding animal welfare, as well as potential risks for disease transmission. Follicle stimulating hormone (FSH) controls the follicular growth and maturation in the porcine ovary under physiological conditions. In the current study, we developed a novel long-acting recombinant porcine FSH (rpFSH-pFc) consisting of porcine FSH and porcine fragment crystallizable (Fc) via (G4S)3 linker by using the available protein fusion technology to control the follicular development and maturation. The results of pharmacokinetic studies indicated that rpFSH-pFc exhibited a prolonged half-life in both rats and sows. The efficacy of rpFSH-pFc was confirmed by cAMP level evaluation and germinal vesicle breakdown (GVBD) analysis in vitro. Through ovarian weight gain, superovulation and fertility testing assays, our results revealed that a single rpFSH-pFc treatment could effectively promote follicular development and maturation in vivo. Meanwhile, the mRNA expression levels of the target genes associated with follicular development, maturation and ovulation were significantly up-regulated after rpFSH-pFc treatment. Taken together, our results revealed that rpFSH-pFc could bind to the FSH receptor, stimulate follicular growth and development in female mice, and possess a prolonged half-life in both rats and sows. These characteristics suggest that rpFSH-pFc may be an ideal candidate for promoting follicular growth and development in livestock production.https://doi.org/10.1038/s41598-025-89356-8Estrous synchronizationFollicular developmentReproductive hormoneRecombinant FSHSwine
spellingShingle Jiawei Zhang
Lei Shi
Xiaorong Zhong
Yunhe Bai
Jun Dou
Lu Zhang
Xiaochao Shi
Bingchun Wu
Zemin Tan
Lin Yan
Jinku Yu
Jingru Zhang
Guo Han
Jiansheng Xiong
Hua Zhang
Xingyuan Cao
Haoshu Luo
Development of highly bioactive long-acting recombinant porcine FSH for batch production management of sows
Scientific Reports
Estrous synchronization
Follicular development
Reproductive hormone
Recombinant FSH
Swine
title Development of highly bioactive long-acting recombinant porcine FSH for batch production management of sows
title_full Development of highly bioactive long-acting recombinant porcine FSH for batch production management of sows
title_fullStr Development of highly bioactive long-acting recombinant porcine FSH for batch production management of sows
title_full_unstemmed Development of highly bioactive long-acting recombinant porcine FSH for batch production management of sows
title_short Development of highly bioactive long-acting recombinant porcine FSH for batch production management of sows
title_sort development of highly bioactive long acting recombinant porcine fsh for batch production management of sows
topic Estrous synchronization
Follicular development
Reproductive hormone
Recombinant FSH
Swine
url https://doi.org/10.1038/s41598-025-89356-8
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