The efficacy of recombinant equine follicle stimulating hormone (reFSH) to promote follicular growth in mares using a follicular suppression model

Jennings, Myra; Boime, Irving; Daphna-Iken, Dorit; Jablonka‐Shariff, Albina; Conley, Alan J; Colgin, M.; Bidstrup, L.A.; Meyers-Brown, Geraldine; Tr, Famula; Roser, Janet F.

doi:10.1016/j.anireprosci.2009.01.013

Cited by 27 publications

(19 citation statements)

References 50 publications

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“…; Jennings et al. ; Yoon and Roser ). The primary antibodies were as follows: sheep antitestosterone‐11‐BSA (#250, G.Niswender, Colorado State University); sheep antiestradiol‐17 β ‐6BSA (#244, G.Niswender, Colorado State University); mouse antibovine LH monoclonal antibody (518B7; Roser, UC Davis, CA, USA); NIDDK anti‐human FSH‐6 (A.F.Parlow; National Hormone and Peptide Program, Harbor‐UCLA Medical Center, Torrence, CA, USA); rabbit IgG raised against 31 kDa bovine inhibin (rAs, #1989; Roberston, Monash University, Clayton, Vic., Australia).…”

Section: Methodsmentioning

confidence: 98%

Acute and Chronic Effects of a Contraceptive Compound RTI‐4587‐073(l) on Testicular Histology and Endocrine Function in Miniature Horse Stallions

Pozor

Zambrano

Roser

et al. 2014

Reprod Domestic Animals

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The objective of this study was to evaluate acute endocrine effects as well as histological changes in testicular parenchyma induced by the contraceptive compound RTI-4587-073(l). Six miniature stallions were used in this experiment. The treatment group (n = 3) received one oral dose of 12.5 mg/kg of RTI-4587-073(l), and the control group (n = 3) received placebo only. The stallions' baseline parameters (semen, testicular dimensions, endocrine values) were collected and recorded for 5 weeks before treatment and for 6 weeks after treatment. Multiple blood samples were collected for endocrine analysis. Testicular biopsies were obtained before treatment, 1 day after treatment and every other week after treatment. Ultrasound exams were performed to monitor the dimensions of the stallions' testes. All stallions were castrated 6 weeks after treatment. Sperm numbers, motility and percentage of morphologically normal sperm decreased (p < 0.05), while the number of immature germ cells increased in ejaculates from treated animals (p < 0.05). Serum concentrations of inhibin and follicle-stimulating hormone did not change. Testosterone concentrations initially transiently decreased (p < 0.05) after administration of RTI-4587-073(l), and increased several days later (p < 0.05). Testicular content of testosterone and estradiol 17-β was lower in treated stallions than in control stallions on Day 1 after treatment (p < 0.05). Severe disorganization of the seminiferous tubules, significant loss of immature germ cells and complete depletion of elongated spermatids were observed in testicular biopsies obtained from treated stallions 1 day, 2 and 4 weeks after treatment. These changes were still present in the testicular samples taken from treated stallions after castration. The results of this study confirmed that RTI-4587-073(l) has antispermatogenic effects in stallions. Furthermore, we concluded that this compound causes acute sloughing of immature germ cells from the seminiferous tubules. RTI-4587-073(l) has significant but transient effects on Leydig cell function in stallions.

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Section: Methodsmentioning

confidence: 98%

Acute and Chronic Effects of a Contraceptive Compound RTI‐4587‐073(l) on Testicular Histology and Endocrine Function in Miniature Horse Stallions

Pozor

Zambrano

Roser

et al. 2014

Reprod Domestic Animals

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“…2.4.1. Inhibins were determined by RIA essentially as previously described and validated [16,17] Inhibin from bovine follicular fluid (bINH-I-90/1; Robertson, Monash University, Clayton, Victoria, Australia) was used for iodination, and standards were derived from dilutions of equine follicular fluid calibrated against bovine inhibin protein, which ranged from 0.15 to 10 ng/mL. The primary antibody was raised in rabbits against 31-kDa bovine inhibin (rAs, #1989; Robertson, Monash University, Clayton, Victoria, Australia).…”

Section: Radio-immunoassaysmentioning

confidence: 99%

“…Concentrations of FSH were determined using a previously validated RIA [16], with slight modifications. Highly purified Table 1 Sensitivities, and intra-and inter-assay co-efficients of variation (from n ¼ 36 determinations at each of two different concentrations) for inhibin-A, inhibin-B and total inhibin ELISAs.…”

Section: Follicle Stimulating Hormone (Fsh)mentioning

confidence: 99%

Inhibin-A and inhibin-B in cyclic and pregnant mares, and mares with granulosa-theca cell tumors: Physiological and diagnostic implications

et al. 2018

Self Cite

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Studies in mares have examined serum inhibin concentrations using immuno-assays unable to distinguish dimeric inhibin-A from inhibin-B isoforms. Inhibin-A and inhibin-B immuno-assays were used to investigate concentrations in cyclic mares, young and old (6 vs 19 years old, respectively) mares following hemi-ovariectomy, mares during pregnancy and in mares with confirmed granulosa cell tumors (GCTs). Mares with inter-ovulatory intervals of 26 days had ovulatory peaks of inhibin-A averaging 80 pg/mL with a mid-cycle nadir of 5 pg/mL. Inhibin-A and inhibin-B concentrations were highly correlated (r = + 0.79, P < 0.01) though peak and nadir concentrations of inhibin-B were not significantly different. However, the ratio of inhibin-A to inhibin-B (A/B) changed significantly through the cycle, highest at ovulation and <1 (more inhibin-B than -A) at mid-cycle. Two mares with grossly extended inter-ovulatory intervals demonstrated mid-cycle inhibin-A (and inhibin-B) excursions suggestive of follicular waves. Follicle-stimulating hormone was negatively correlated with inhibin-A and -B concentrations in all 6 mares. Hemi-ovariectomy in young mares resulted in a significant decrease in inhibin-A and inhibin-B concentrations one day later (P < 0.05) but older mares did not, suggesting a possible extra-ovarian source(s) of these hormones. Both inhibin isoforms dropped to very low levels during pregnancy (P < 0.0001), inhibin-A (P < 0.0001) more rapidly than -B (P < 0.05), so that inhibin-B became the predominant measured form throughout most of gestation (P < 0.05). Mares with confirmed GCTs had elevated inhibin-B concentrations more reliably than inhibin-A but neither inhibin-A or -B was correlated with anti-Müllerian hormone concentrations. Collectively, concentrations of inhibin-A and -B were aligned with physiological events in healthy mares, though more pronounced cyclic changes were seen with inhibin-A. Inhibin-B concentrations were significantly associated with GCTs (P < 0.01), inhibin-A concentrations were not. While both inhibin-A and -B concentrations track physiological events such as cyclic follicular activity, only inhibin-B concentrations effectively signal ovarian neoplasia in mares.

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“…In some cases, human embryonic kidney (HEK) cells have been chosen as a cell factory to produce bovine FSH (Nanocore Biotecnologia SA) used to supplement culture medium for in vitro follicle development in mares [29], dogs [30], goats, and sheep [31] (Table 1). The equine reproduction research industry has clearly been a user and promoter of this drug to stimulate follicular growth [6, 19, 32, 33] and ovulation [34] in mares. Even so, although the human version of this long-acting and single-chain FSH, Elonva (Corifollitropin α; MSD) was already available in 1992 [35–38], the bovine and equine analogs did not reach the market until 2008 [6].…”

Section: Recombinant Hormones In Reproductionmentioning

confidence: 99%

“…The CG has a longer region because of a peptide called carboxyl terminal peptide (CTP) that provides the CG with more glycosylation places and prolong CG half-life by reducing its renal clearance [56]. These extra glycosylation sites have been fused to FSH [6, 19, 32–34] and LH [21, 24, 57–59], which do not naturally contain this sequence, to achieve long-acting hormones. This allowed the reduction in the number of injections for superovulation treatments [13, 36, 40].…”

Section: Recombinant Hormones In Reproductionmentioning

confidence: 99%

Trends in recombinant protein use in animal production

et al. 2017

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Recombinant technologies have made possible the production of a broad catalogue of proteins of interest, including those used for animal production. The most widely studied proteins for the animal sector are those with an important role in reproduction, feed efficiency, and health. Nowadays, mammalian cells and fungi are the preferred choice for recombinant production of hormones for reproductive purposes and fibrolytic enzymes to enhance animal performance, respectively. However, the development of low-cost products is a priority, particularly in livestock. The study of cell factories such as yeast and bacteria has notably increased in the last decades to make the new developed reproductive hormones and fibrolytic enzymes a real alternative to the marketed ones. Important efforts have also been invested to developing new recombinant strategies for prevention and therapy, including passive immunization and modulation of the immune system. This offers the possibility to reduce the use of antibiotics by controlling physiological processes and improve the efficacy of preventing infections. Thus, nowadays different recombinant fibrolytic enzymes, hormones, and therapeutic molecules with optimized properties have been successfully produced through cost-effective processes using microbial cell factories. However, despite the important achievements for reducing protein production expenses, alternative strategies to further reduce these costs are still required. In this context, it is necessary to make a giant leap towards the use of novel strategies, such as nanotechnology, that combined with recombinant technology would make recombinant molecules affordable for animal industry.

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The efficacy of recombinant equine follicle stimulating hormone (reFSH) to promote follicular growth in mares using a follicular suppression model

Cited by 27 publications

References 50 publications

Acute and Chronic Effects of a Contraceptive Compound RTI‐4587‐073(l) on Testicular Histology and Endocrine Function in Miniature Horse Stallions

Acute and Chronic Effects of a Contraceptive Compound RTI‐4587‐073(l) on Testicular Histology and Endocrine Function in Miniature Horse Stallions

Inhibin-A and inhibin-B in cyclic and pregnant mares, and mares with granulosa-theca cell tumors: Physiological and diagnostic implications

Trends in recombinant protein use in animal production

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