Description

Ovagen Peptide

 

 

CAS Number	N/A
Other Names	Glu-Asp-Leu, glutamyl-aspartyl-leucin, NH2-Glu-Asp-Leu-COOH, SCHEMBL5329396
IUPAC Name	(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-carboxybutanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoic acid
Molecular Formula	C₁₅H₂₅N₃O₈
Molecular Weight	375.37
Purity	≥99% Pure (LC-MS)
Liquid Availability	N/A
Powder Availability	10 milligrams vial (lyophilized/freeze-dried)
Storage Condition	Store cold, keep refrigerated. Do NOT freeze.
Terms	All products are for laboratory developmental research USE ONLY. Products are not for human consumption.

**Important Information: Each peptide comes lyophilized/freeze-dried and must be reconstituted with Bacteriostatic Water in order to be dispensable in liquid form.

Watch How To Reconstitute Peptide Video Here

 

What is Ovagen?

Ovagen is a naturally derived bioactive peptide recognized for its potent regenerative, immunomodulatory, and cytoprotective properties. Composed of low-molecular-weight peptides and nucleoprotein fragments, Ovagen has been studied for its ability to stimulate cellular repair processes, enhance protein synthesis, and support tissue regeneration in damaged or aging cells. Its unique composition enables it to modulate immune responses, reduce inflammation, and promote recovery of epithelial and connective tissues, making it valuable in dermatology, gastroenterology, and hepatology. Additionally, Ovagen exhibits antioxidant and radioprotective activities, contributing to its protective effects against cellular stress and toxicity. These characteristics position Ovagen as a promising therapeutic peptide for use in regenerative medicine and as a supportive agent in treating tissue injury and degenerative diseases.

 

Main Research

1) Administration of low doses of Ovagen were shown to improve impaired functioning of ovarian follicles and closed oocytes in dairy cows.

2) When administered to female sheep, Ovagen was shown to promote natural cervix relaxation to allow for optimal intrauterine penetration.

 

 

Selected Data
1) The study was conducted by the research team of Friedman et al to investigate the effects of the peptide Ovagen, a low-dose follicle-stimulating hormone (FSH) preparation, on follicular development and function in heifers and lactating dairy cows. A series of three experiments were designed to evaluate Ovagen’s efficacy in promoting follicular growth, its influence on preovulatory follicle characteristics, and potential carryover effects on subsequent reproductive cycles [1].
Estrous cycles of all experimental animals were synchronized using two, 625 μg intramuscular injections of prostaglandin F₂α (PGF₂α) analogue, cloprostenol, administered at 13-day intervals for cows and 11-day intervals for heifers. Estrous behavior was monitored visually four times daily for two days beginning 24 hours after the second PGF₂α injection. Only animals exhibiting standing estrus were included in the experiments. Follicular dynamics were tracked using transrectal ultrasonography equipped with a 7.5 MHz linear probe to record the number and size of small follicles ranging from 3–6 mm, and larger follicles >6 mm throughout the cycle [1].
Cows were sedated with 14 mg intramuscular xylazine and received epidural anesthesia with lidocaine to relax the rectovaginal area. Under ultrasound guidance, individual follicles were aspirated using a 7.5 MHz vaginal probe fitted with a needle guide and 5 mL syringe. The follicular fluid from each follicle was collected separately and stored at –20°C for subsequent analysis. Concentrations of key reproductive hormones such as progesterone, estradiol, androstenedione, and insulin were determined by radioimmunoassay (RIA) using validated methods. Estradiol and progesterone were quantified in both plasma and follicular fluid with commercial RIA kits, while androstenedione and insulin were measured using diagnostic RIA kits according to manufacturer protocols.
The first experiment aimed to determine whether low doses of Ovagen or a conventional FSH preparation, Folltropin-V, could enhance follicular development in a defined follicular wave. Conducted during the cool season to minimize environmental stress, the trial used 11–15-month-old cyclic Holstein heifers maintained under controlled feeding conditions. Heifers were randomly assigned to Ovagen, Folltropin, or control groups. Both Ovagen and Folltropin were administered intramuscularly for three consecutive days defined as cycle days 3–5. Folltropin doses totaled 120 mg administered at 100, 10, and 10 mg/day, while Ovagen totaled 5.28 mg administered at 4.4, 0.44, and 0.44 mg/day. These doses represented 25% of those used in standard superovulation protocols. Daily ultrasound scans monitored follicular growth during the treatment period [1].
The second experiment examined whether short-term, low-dose Ovagen administration could improve preovulatory follicle quality under heat stress conditions. Conducted in summer, the study used lactating Holstein cows under a cooling regimen, averaging 180 ± 17 days in milk and producing 32.8 ± 1.3 kg milk per day. Cows were randomly allocated to control, 2.2 mg Ovagen (FSH-2.2), or 4.4 mg Ovagen (FSH-4.4) groups. Treatments were given on days 3–4 and 10–11 of the estrous cycle, corresponding to natural peaks in endogenous FSH. PGF₂α was administered on day 17 to induce luteolysis, and all large follicles ≥10 mm were aspirated 40 hours later. Follicular growth was monitored on days 3–6, 10–13, and 17, while blood was collected at multiple time points across the cycle for hormonal analysis [1].
The third experiment investigated whether administering 4.4 mg Ovagen during one cycle could influence the first-wave preovulatory follicle of the following cycle. Conducted during summer 2008 under similar thermal and dietary conditions, 12 lactating cows were paired based on parity and production before random allocation to control or Ovagen groups. The first FSH injection occurred on day 3, and the second on days 12–13 of the estrous cycle to optimize synchronization with endogenous FSH secretion. PGF₂α was administered on day 18, followed by gonadotropin-releasing hormone (GnRH) on day 20 to induce ovulation. Another PGF₂α dose was given on day 6 of the next cycle to regress the corpus luteum before follicular aspiration 40 hours later. Follicular growth and blood hormone levels were closely monitored throughout the treated and subsequent cycles [1].
Overall, this experimental design allowed detailed evaluation of Ovagen’s role as a low-dose FSH analogue in modulating follicular development, endocrine responses, and reproductive performance in dairy cattle under varying physiological and environmental conditions.

2) The study completed by Leethongdee et al investigated cervical penetrability and morphological changes in the reproductive tract of parous Welsh Mountain ewes, with a focus on the effects of the peptide Ovagen (ovine follicle-stimulating hormone, FSH) and the prostaglandin E₁ analogue misoprostol.
Two separate experiments were conducted using healthy, parous Welsh Mountain ewes. The first experiment involved 24 ewes randomly assigned to six groups of four animals each. The study was conducted in three replicates, allowing for twelve observations per treatment group. After each replicate, the ewes were given a five-day rest period before starting the next treatment cycle. The second experiment included 18 ewes that were divided into four groups of four or five animals each. This trial was replicated twice, providing nine total observations per treatment. In both experiments, ewes were re-randomized between replicates, and the resulting data were treated as independent. All animals were housed indoors in groups of six to eight on straw bedding, with free access to hay, water, and a commercial concentrate feed [2].
To standardize reproductive status, all ewes underwent synchronization of their estrous cycles. This was achieved using intravaginal progesterone-impregnated sponges that remained in place for 12 days, followed by administration of pregnant mare serum gonadotropin (PSMG) at sponge removal to stimulate follicular development and induce estrus. The PMSG dose was 250 IU in the first experiment and 500 IU in the second experiment to account for potential differences in reproductive activity between seasons.
Cervical penetration tests were conducted to evaluate how far a sounding device could pass into the cervix under gentle manipulation. The ewes were restrained in a yoke equipped with sidebars to limit movement, with their hindquarters slightly elevated. The measuring device was a modified stainless-steel artificial insemination pipette. The sheath was 42 cm long and 3.0 mm in external diameter, while the inner plunger was 10 cm longer and etched with 0.5 cm graduations on its distal end. The rounded metal tip allowed smooth insertion without tissue injury. After cleaning the perineal area with disinfectant and visualizing the cervix using a speculum and lamp, the pipette tip was placed at the external cervical os. The plunger was advanced as far as possible without applying force, and the distance advanced beyond the sheath was recorded as the depth of cervical penetration. Penetrations exceeding 8 cm were considered intrauterine. Each measurement was taken in duplicate to ensure accuracy [2].
In the first experiment, the effect of time after sponge removal on cervical penetrability was studied. Five groups of ewes (Groups 1–5) underwent penetration testing only once, at 0, 24, 48, 72, or 96 hours post-sponge removal (“once-only” groups). A sixth group (Group 6) was examined at each of those time points (“repeated” group) to assess how repeated testing influenced cervical response over time. The second experiment examined whether intra-cervical treatment with Ovagen, misoprostol, or their combination affected cervical penetrability and mucus characteristics. Cervical penetration was assessed at 24, 48, 54, 60, 66, and 72 hours after sponge removal. The ewes were randomly assigned to four treatment groups: Ovagen group, receiving 2 mg of intra-cervical ovine FSH in 0.5 mL of 50% gum acacia at 24 hours post-sponge removal, followed by a vehicle control (gelatin) at 48 hours; Misoprostol group, receiving a gum acacia vehicle at 24 hours and 1 mg of misoprostol in 0.5 mL of 30% gelatin at 48 hours; Ovagen + Misoprostol group, treated with Ovagen at 24 hours and misoprostol at 48 hours post-sponge removal; and control group, receiving vehicle-only treatments of gum acacia at 24 hours and gelatin at 48 hours [2].
Treatments were administered using a 1 mL pipette fitted with a 10 cm blunted extension made by gluing together three 1000 μL tips. The extension was sterilized before use, and approximately 0.5 mL of the treatment bolus was deposited 2–4 cm into the cervical canal under speculum guidance. When deep insertion was not possible, the dose was placed at the cervical os. Preliminary tests confirmed that the 0.5 mL bolus volume and vehicle viscosity prevented leakage from the cervical canal.
Samples of cervical mucus were collected by gentle suction using a syringe fitted with a long, flexible plastic tube. The mucus was smeared onto glass slides, air-dried, and examined microscopically. The crystallization, or “ferning,” pattern of the mucus is an indicator of estrogenic activity and was classified into three categories: (i) incomplete or atypical ferning, (ii) complete or typical ferning, and (iii) degraded ferning. These observations helped to correlate hormonal status and cervical mucus properties with cervical penetrability at different time points and treatment conditions [2].
In summary, this controlled series of experiments used synchronized ewes to systematically assess how timing, hormonal treatment with Ovagen, and cervical softening agents like misoprostol influence cervical morphology, mucus properties, and the depth of cervical penetration, factors that are critical for improving the success of intrauterine insemination [2].

 

Discussion
1) The study performed by Friedman et al evaluated the effects of the peptide Ovagen, a low-dose FSH preparation, on follicular development and endocrine parameters in heifers and lactating dairy cows across three experiments.
The first portion of the experiment investigated whether low doses of exogenous FSH, administered as either Folltropin-V or Ovagen, could enhance early follicular growth. Results showed that both treatments significantly increased the number of medium-sized follicles ≥6 mm in diameter, compared to untreated controls. On day 6 of the estrous cycle, the mean number of follicles ≥6 mm was 5.83 ± 0.77 in the Ovagen group and 6.71 ± 0.72 in the Folltropin group, compared to only 3.42 ± 0.55 in the control group. This finding indicated that low-dose FSH administration successfully promoted follicular recruitment and development at a stage corresponding to the spontaneous emergence of the first follicular wave [1].
The second portion of the experiment examined whether Ovagen affected hormonal profiles and follicular dynamics during the estrous cycle in lactating cows. Treatment with Ovagen at 2.2 mg (FSH-2.2) or 4.4 mg (FSH-4.4) did not significantly alter plasma concentrations of progesterone or estradiol. Average plasma progesterone levels were 2.95 ± 0.53 ng/mL, 3.59 ± 0.43 ng/mL, and 3.37 ± 0.47 ng/mL in control, FSH-2.2, and FSH-4.4 cows, respectively, while estradiol levels were 2.36 ± 0.31 pg/mL, 1.64 ± 0.25 pg/mL, and 1.98 ± 0.28 pg/mL. Although hormone profiles remained unchanged, the higher Ovagen dose (4.4 mg) tended to increase the number of follicles ≥6 mm at the time of the first follicular wave’s emergence. On day 6, FSH-4.4–treated cows had more than twice as many medium-sized follicles as controls. However, Ovagen did not significantly affect the number of follicles emerging in the second follicular wave, possibly due to prolonged dominance of the first-wave dominant follicle, which extended by approximately three days [1].
Follicle size measurements revealed no statistically significant differences in the diameter of dominant or preovulatory follicles between control and treated groups. The dominant follicle of the second wave appeared about two days earlier in control cows than in treated cows, although this difference was not significant. The preovulatory follicle aspirated on day 16 of the estrous cycle was slightly larger in control cows than in Ovagen-treated cows, but this difference was also nonsignificant. Because no major differences were detected between the two Ovagen doses, data from the FSH-2.2 and FSH-4.4 groups were pooled for further analysis. In some treated cows, the second follicular wave did not emerge until the last day of ultrasound monitoring, leading to missing data for those animals.
Analysis of follicular fluid showed no significant differences between groups in estradiol, progesterone, or androstenedione concentrations. Estradiol levels were 836 ± 198, 659 ± 177, and 844 ± 229 ng/mL for control, FSH-2.2, and FSH-4.4 groups, respectively. Progesterone concentrations were 51 ± 10, 57 ± 9, and 75 ± 12 ng/mL, while androstenedione levels were 86 ± 39, 77 ± 35, and 81 ± 45 ng/mL across the same groups. Notably, insulin concentration in the follicular fluid tended to be higher in FSH-4.4 cows at 1114 ± 543 pg/mL, compared to controls at 378 ± 145 pg/mL, and FSH-2.2 cows at 303 ± 90 pg/mL. This suggested a potential metabolic effect of Ovagen on intrafollicular insulin levels, which may influence follicular metabolism and oocyte development [1].

Figure 1: Changes in concentrations of estradiol and progesterone in control and FSH-4.4 groups.
The third part of the experiment assessed the carryover effects of 4.4 mg Ovagen on follicular activity in subsequent cycles. Ovagen again increased the number of medium-sized follicles ≥6 mm, particularly on days 5 and 6 of the estrous cycle. Plasma progesterone and estradiol profiles were not significantly affected, although progesterone levels tended to be approximately 2 ng/mL higher in treated cows on days 16 and 18. The number of small follicles at the start of the second follicular wave was greater in control cows than in FSH-treated cows, but in Ovagen-treated cows, the number of small follicles increased significantly two to three days after the second FSH administration, indicating a delayed but enhanced recruitment effect. The maximum diameter of the dominant follicle from the first wave tended to be larger in controls measuring at 17.5 ± 1.2 mm than in Ovagen-treated cows measuring at 14.1 ± 1.1 mm. The size of the dominant follicle of the second wave and of the preovulatory follicle in the subsequent cycle did not differ significantly between groups [1].

Figure 2: Changes in the number of follicles ≥6 mm in control and FSH-4.4 groups.
Finally, hormonal analysis of preovulatory follicles confirmed estrogenic activity, with estradiol-to-progesterone ratios greater than one across all samples. Concentrations of estradiol, progesterone, and insulin in follicular fluid did not differ significantly between control and FSH-4.4 cows, averaging 992 ± 161 vs. 1201 ± 176 ng/mL estradiol, 124 ± 19 vs. 118 ± 21 ng/mL progesterone, and 74 ± 34 vs. 119 ± 34 pg/mL insulin, respectively.
In summary, low-dose Ovagen administration effectively stimulated the early recruitment of medium-sized follicles without disrupting the natural endocrine balance of progesterone and estradiol. Ovagen demonstrated a consistent trend toward enhanced follicular growth, supporting its potential as a mild FSH analogue for modulating ovarian function in cattle [1].
2) The experiments performed by Leethongdee et al evaluated how cervical penetration depth and cervical physiological changes varied in Welsh Mountain ewes following synchronization of oestrus and treatment with intra-cervical agents, including the peptide Ovagen and the prostaglandin analogue Misoprostol.
The first experiment examined natural changes in cervical penetrability after oestrous synchronization using progestagen sponges and PMSG. Significant time-dependent variation in the depth of cervical penetration was observed. In ewes examined once at each time point, mean penetration depth increased from 0.73 ± 0.28 cm at sponge removal (0 hours) to a peak of 5.0 ± 1.2 cm at 72 hours, followed by a sharp decline to 1.6 ± 0.84 cm by 96 hours. This increase from sponge removal to 72 hours was highly significant, with penetration depth significantly reduced at 96 hours compared to 72 hours. A similar pattern was observed in the “repeated” group, in which the same ewes were tested multiple times: penetration increased from 0.56 ± 0.15 cm at 0 hours to 6.2 ± 1.2 cm at 72 hours before declining thereafter. Depth of penetration at 0 hours was significantly lower than at all later times. Although the progression between 24 and 72 hours was gradual, differences among those times were not statistically significant. Comparison between groups showed no difference in penetration at 0–72 hours, but at 96 hours penetration depth remained higher in the repeated group, suggesting that repeated manipulation may have contributed to slightly greater penetrability at later time points [2].
Cervical mucus production and characteristics also varied with time. At 24 hours, all ewes exhibited some mucus discharge, and by 72 hours, half of the ewes had copious mucus flow, coinciding with peak cervical penetration and estrogenic activity. By 96 hours, mucus flow diminished, with 75% showing some discharge and 25% none. The color of cervical mucus shifted from predominantly yellow at 24 hours to mostly clear at 48 hours, remained largely clear or slightly pink-tinged at 72 hours, and returned to a thicker, yellow appearance by 96 hours, consistent with the luteal phase. Microscopic examination of mucus smears revealed changing ferning patterns characteristic of hormonal fluctuations. Partial ferning appeared at 24 hours, complete ferning at 48 hours (indicating high estrogen levels), partial degradation by 72 hours, and complete loss of ferning by 96 hours, reflecting declining estrogen and increasing progesterone concentrations.
The second experiment examined the effects of intra-cervical administration of Ovagen, the ovine FSH peptide, Misoprostol, a prostaglandin E1 analogue, or their combination on cervical penetration. Penetrability was significantly affected by both time and treatment, though the interaction between them was not significant. In control ewes, penetration depth was lowest at 24 hours and peaked at 72 hours. In contrast, ewes treated with Ovagen alone exhibited a more rapid and pronounced increase in penetration, reaching maximal intrauterine penetration between 54 and 60 hours in all animals, followed by a decline at 66 and 72 hours. Misoprostol-treated ewes showed a similar trend, with lowest penetration at 24 hours, maximal penetration at 54 hours, and subsequent decline. The combination of Ovagen and Misoprostol produced comparable results, with maximum penetration also at 54 hours [2].

Figure 3: Depth of penetration of the cervix at varying times following sponge removal during the peri-ovulatory phase
Additional qualitative observations revealed that control ewes reached peak penetrability later at 72 hours, while Ovagen and Misoprostol treatments accelerated cervical softening and dilation, achieving maximal penetration earlier at 54 hours. Ovagen treatment appeared to sustain intrauterine penetration longer than Misoprostol or the combination treatment. Furthermore, the external cervical os was visibly more dilated in Ovagen- and Misoprostol-treated ewes, and penetration was technically easiest in the combination group, followed by Ovagen, Misoprostol, and then control ewes. Ovagen treatment was also associated with increased production of thin, watery mucus, suggesting enhanced cervical relaxation and secretory activity [2].
Overall, these experiments demonstrate that cervical penetration in ewes follows a predictable peri-ovulatory pattern influenced by hormonal changes, and that intra-cervical Ovagen and Misoprostol significantly enhance cervical softening, mucus secretion, and penetrability, facilitating intrauterine access earlier in the oestrous cycle compared to untreated controls [2].

 

Disclaimer

**LAB USE ONLY**
*This information is for educational purposes only and does not constitute medical advice. THE PRODUCTS DESCRIBED HEREIN ARE FOR RESEARCH USE ONLY. All clinical research must be conducted with oversight from the appropriate Institutional Review Board (IRB). All preclinical research must be conducted with oversight from the appropriate Institutional Animal Care and Use Committee (IACUC) following the guidelines of the Animal Welfare Act (AWA).

 

Citations

[1] Friedman E, Glick G, Lavon Y, Roth Z. Effects of low-dose follicle-stimulating hormone administration on follicular dynamics and preovulatory follicle characteristics in dairy cows during the summer. Domest Anim Endocrinol. 2010;39(2):106-115. doi:10.1016/j.domaniend.2010.02.008

[2] Leethongdee S, Khalid M, Bhatti A, Ponglowhapan S, Kershaw CM, Scaramuzzi RJ. The effects of the prostaglandin E analogue Misoprostol and follicle-stimulating hormone on cervical penetrability in ewes during the peri-ovulatory period. Theriogenology. 2007;67(4):767-777. doi:10.1016/j.theriogenology.2006.10.012

 

 

PEPTIDES PREFER THE COLD
Keep peptide vials refrigerated at all times to reduce peptide bond breakdown. DO NOT FREEZE. Most peptides, especially shorter ones, can be preserved for weeks if careful.
Always swab the top of the vial with an alcohol wipe, rubbing alcohol or 95% ethanol before use.
Before drawing solution from any dissolved peptide vial, fill the pin with air to the same measurement you will be filling with solution, ie. if you plan to take 0.1 ml, first fill the pin with 0.1ml of air, push the air into the vial, and then draw the peptide back up to the 0.1 ml marker. Doing so will maintain even pressure in the vial. Always remember to remove air bubbles from the pin by flicking it gently, pin side up, and pushing bubbles out. In addition, push out a tiny amount of solution to ensure there is no air left in the metal tip.

ONLY MIX WITH STERILE BACTERIOSTATIC WATER
The purity and sterility of bacteriostatic water are essential to prevent contamination and to preserve the shelf-life of dissolved peptides.
Push the pin through the rubber stopper at a slight angle, so that you inject the bacteriostatic water toward the inside wall of the vial, not directly onto the powder.
Lyophilized peptide should be stored at -20°C (freezer), and the reconstituted peptide solution at 4°C (refrigerated). Do not freeze once reconstituted.
NEVER SHAKE A VIAL TO MIX.

Air bubbles are unfavorable to the stability of proteins.

Ovagen is sold for laboratory research use only. Terms of sale apply. Not for human consumption, nor medical, veterinary, or household uses. Please familiarize yourself with our Terms & Conditions prior to ordering.

 

 

 

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