دورية أكاديمية

Antibody fragments targeting the extracellular domain of follicular stimulating hormone receptor for contraception in male dogs and cats.

التفاصيل البيبلوغرافية
العنوان: Antibody fragments targeting the extracellular domain of follicular stimulating hormone receptor for contraception in male dogs and cats.
المؤلفون: Navanukraw P; Department of Obstetrics, Gynaecology and Reproduction, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand., Chotimanukul S; Department of Obstetrics, Gynaecology and Reproduction, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand., Udomthanaisit L; Department of Obstetrics, Gynaecology and Reproduction, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand., Setthawong P; Department of Physiology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, Thailand., Saehlee S; Department of Biochemistry, Faculty of Science, Kasetsart University, Bangkok, Thailand., Seetaha S; Department of Biochemistry, Faculty of Science, Kasetsart University, Bangkok, Thailand., Choowongkomon K; Department of Biochemistry, Faculty of Science, Kasetsart University, Bangkok, Thailand. Electronic address: fsciktc@ku.ac.th., Chatdarong K; Department of Obstetrics, Gynaecology and Reproduction, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand. Electronic address: kaywalee.c@chula.ac.th.
المصدر: Theriogenology [Theriogenology] 2024 Sep 15; Vol. 226, pp. 110-119. Date of Electronic Publication: 2024 Jun 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 0421510 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3231 (Electronic) Linking ISSN: 0093691X NLM ISO Abbreviation: Theriogenology Subsets: MEDLINE
أسماء مطبوعة: Publication: [New York, N.Y.?] : Elsevier
Original Publication: Los Altos, Calif., Geron-X.
مواضيع طبية MeSH: Receptors, FSH*/metabolism , Receptors, FSH*/genetics , Receptors, FSH*/immunology, Animals ; Dogs ; Cats ; Male ; Contraception/veterinary ; Contraception/methods ; Sertoli Cells/metabolism
مستخلص: The increased LH levels resulting from the absence of negative feedback after castration has been linked to long-term health issues. A need exists for an alternative contraceptive agent that functions without interfering the LH pathways. This study aimed to develop antibody fragments against the follicular-stimulating hormone receptor (anti-FSHr) using phage-display technology and evaluate its effects on Sertoli cell functions. Phage clones against the extracellular domain of dog and cat FSHr selected from an antibody fragment phagemid library were analyzed for binding kinetics by surface plasmon resonance. Sertoli cells were isolated from testes of adult animals (five dogs and five cats). Efficacy test was performed by treating Sertoli cell cultures (SCCs) with anti-FSHr antibody fragments compared with untreated in triplicates. Expressions of androgen binding protein (ABP), inhibin subunit beta B (IHBB) and vascular endothelial growth factor A (VEGFA) mRNA in SCCs were quantified by RT-qPCR. The results demonstrated that the molecular weight of the purified dog and cat anti-FSHr antibody fragment was 25 kDa and 15 kDa, respectively. Based on protein molecular weight, the antibody fragment of dogs and cats was therefore, so-called single-chain variable fragments (scFv) and nanobody (nb), respectively. The binding affinity with dissociation constant (K D ) was 2.32 × 10 -7  M and 2.83 × 10 -9  M for dog and cat anti-FSHr antibody fragments, respectively. The cross-binding kinetic interactions between the dog anti-FSHr scFv and the cat ECD of FSHr could not be fitted to the curves to determine the binding kinetics. However, the cross-binding affinity K D between the cat anti-FSHr nb and the dog ECD FSHr was 1.75 × 10 -4  M. The mRNA expression of ABP, IHBB and VEGFA in SCCs was less (P < 0.05) in both dogs (12.26, 4.07 and 5.11 folds, respectively) and cats (39.53, 14.07 and 20.29 folds, respectively) treated with anti-FSHr antibody fragments, indicating the Sertoli cell functions were suppressed. In conclusion, this study demonstrated the establishment of species-specific antibody fragments against FSHr in SCCs for dogs and cats. The fragment proteins illustrate potential to be developed as non-surgical contraceptive agent targeting FSHr in companion animals.
Competing Interests: Declaration of competing interest None of the authors have any conflict of interest to declare.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: Antibody fragment; Canine; Contraception; Feline; Species-specific
المشرفين على المادة: 0 (Receptors, FSH)
تواريخ الأحداث: Date Created: 20240614 Date Completed: 20240722 Latest Revision: 20240722
رمز التحديث: 20240723
DOI: 10.1016/j.theriogenology.2024.06.005
PMID: 38875921
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-3231
DOI:10.1016/j.theriogenology.2024.06.005