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Topic:Hormones

Hormones in horses are chemical messengers produced by various glands and tissues, regulating numerous physiological processes essential for maintaining homeostasis. These hormones influence a wide range of functions, including growth, metabolism, reproduction, and stress responses. Key hormones in equine physiology include cortisol, estrogen, testosterone, and insulin, among others. The levels and effects of these hormones can vary based on factors such as age, sex, and environmental conditions, impacting overall health and performance. This page compiles peer-reviewed research studies and scholarly articles that explore the production, regulation, and physiological roles of hormones in equine biology.
Equine chorionic gonadotropin administered on day 5 of a 7-days fixed-time artificial insemination program improves ovulation synchrony and corpus luteum function in anestrous beef cows.
Theriogenology    October 17, 2022   Volume 195 62-68 doi: 10.1016/j.theriogenology.2022.10.016
Aragunde Vieytes R, Viñoles Gil C, Gastal GDA, Cavestany D.In order to assess the effect of equine chorionic gonadotropin (eCG) administered on Day 5 or 7 of a fixed-time artificial insemination protocol (FTAI) in anestrous suckled beef cows, two experiments were performed to determine the following endpoints: Experiment 1 (n = 22), preovulatory follicle (POF) diameter, ovulation time, corpus luteum (CL) area, estradiol (E2) and progesterone (P4) concentrations; and Experiment 2 (n = 676), a field trial to evaluate conception rate using the same experimental design. In both experiments, a synchronization protocol using estradiol benzoate (EB) (Day...
Pituitary Pars Intermedia Dysfunction (PPID) in Horses.
Veterinary sciences    October 10, 2022   Volume 9, Issue 10 556 doi: 10.3390/vetsci9100556
Kirkwood NC, Hughes KJ, Stewart AJ.Substantial morbidity results from pituitary pars intermedia dysfunction (PPID) which is often underestimated by owners and veterinarians. Clinical signs, pathophysiology, diagnostic tests, and treatment protocols of this condition are reviewed. The importance of improved recognition of early clinical signs and diagnosis are highlighted, as initiation of treatment will result in improved quality of life. Future research should be targeted at improving the accuracy of the diagnosis of PPID, as basal adrenocorticotropic hormone (ACTH) concentration can lack sensitivity and thyrotropin releasing ...
The post-ovulatory rise in progesterone is lower and the persistence of oestrous behaviour longer during the first compared with the second cycle of the breeding season in mares.
Reproduction in domestic animals = Zuchthygiene    October 6, 2022   Volume 58, Issue 1 141-145 doi: 10.1111/rda.14273
Newcombe JR, Wilsher S, Cuervo-Arango J.Mares are seasonally polyoestrous breeders. Therefore, the first ovulation of the season, following winter anoestrus, is the only cycle in which mares ovulate without the presence of an old CL from the previous cycle. The objective of this study was to compare the length of oestrous behaviour, and plasma progesterone concentrations during the early post-ovulatory period between mares after the first and second ovulation of the breeding season. Overall, 38 mares and 167 oestrous periods were used in the study. From those, 11 mares were used during the first and subsequent oestrous period to mea...
Endocrine and ovarian responses to combined estradiol benzoate-sulpiride in seasonally anovulatory mares treated with kisspeptin.
Animal reproduction science    September 30, 2022   Volume 247 107087 doi: 10.1016/j.anireprosci.2022.107087
Bailey VN, Sones JL, Camp CM, Gomes VCL, Oberhaus EL.The objective of this experiment was to determine if incorporation of kisspeptin-10 (Kp10) into treatment with estradiol benzoate (EB) and sulpiride to induce early cyclicity would result in greater endocrine responses and a greater number of mares responding with either follicle(s) > 30 mm or ovulation within 25 days of treatment. Eighteen anestrous mares were blocked by breed, body condition, and age before random assignment to treatment or control. All mares received 50 mg EB before receiving osmotic minipumps containing either saline (n = 9) or Kp10 (50 μg/hour; n = 9) one day ...
Blood Profile, Hormones, and Telomere Responses: Potential Biomarkers in Horses Exhibiting Abnormal Oral Behavior.
Journal of equine veterinary science    September 29, 2022   Volume 118 104130 doi: 10.1016/j.jevs.2022.104130
Hanis F, Chung ELT, Kamalludin MH, Idrus Z.The high prevalence of abnormal oral behavior (AOB) in working horses has been linked to management issues and the pathophysiology of this behavior remains unclear. Therefore, this study aims to elucidate the blood profile, hormones, and telomere length responses between low and high levels of AOB among different horse working groups. A total of 207 healthy horses from various breeds were initially selected from four working groups (leisure riding, equestrian, endurance, and patrolling) and observed for the time spent on AOB. Then, six horses each with higher and lower AOB than the population ...
Management of pituitary pars intermedia dysfunction in practice: A clinical audit.
Veterinary journal (London, England : 1997)    September 24, 2022   Volume 289 105899 doi: 10.1016/j.tvjl.2022.105899
Steel NL, Ireland JL, McGowan CM.In horses/ponies with pituitary pars intermedia dysfunction (PPID), pergolide mesylate treatment, with monitoring of therapeutic response, is recommended by contemporaneous literature and equine endocrinologists. However, it is unknown whether these recommendations are adhered to in private practice. This clinical audit aimed to compare treatment and monitoring of PPID cases in veterinary practice against available recommendations. Case data and basal plasma adrenocorticotropic hormone (ACTH) concentrations from all equids tested for PPID between 2012 and 2016 from a single veterinary practice...
Re-stimulation of testicular function in GnRH-vaccinated stallions by daily GnRH agonist treatment.
Theriogenology    September 24, 2022   Volume 194 27-34 doi: 10.1016/j.theriogenology.2022.09.011
Gautier C, Aurich J, Kaps M, Okada CTC, Wagner LH, Melchert M, Aurich C.In stallions temporarily not intended for breeding, reversible suppression of testicular function by vaccination against GnRH can be of interest. In the present study, effects of GnRH agonist treatment on the resumption of testicular function after GnRH vaccination were investigated. Testis size, testosterone release, semen characteristics and behavior were evaluated. We hypothesized that GnRH agonist treatment would restore testicular function. Shetland stallions were assigned to an experimental and a control group (n = 6 each). Experimental stallions were GnRH-immunized twice, four weeks a...
Determination of hair cortisol in horses: comparison of immunoassay vs LC-HRMS/MS.
Analytical and bioanalytical chemistry    September 22, 2022   Volume 414, Issue 28 8093-8105 doi: 10.1007/s00216-022-04343-6
The measure of hair cortisol concentration (HCC) is becoming an emerging approach to monitor mid-/long-term stress in animals, so it is more and more important to develop accurate and reliable methods. In the light of this, the aim of the present study was to compare mane HCCs of 47 horses with different managements, by means of an immunoassay (ELISA) and liquid chromatography coupled to hybrid high-resolution mass spectrometry (LC-HRMS/MS). After the washing step, the ground hair was extracted with methanol. The extract was evaporated and redissolved in two different aqueous solutions, depend...
Effects of equine-assisted interventions on older adults’ health: A systematic review.
International journal of nursing sciences    September 20, 2022   Volume 9, Issue 4 542-552 doi: 10.1016/j.ijnss.2022.09.008
Badin L, Alibran É, Pothier K, Bailly N.Equine-assisted interventions (EAI) can improve a variety of health problems in older adults and thus promote their well-being. This systematic review aimed to synthesize studies on EAI to understand better their effects on the health of older adults. Unassigned: A systematic search guided by the PRISMA 2020 approach was performed on specific databases: Medline (PubMed), EMBASE, PsycINFO, and Cochrane Library. Peer-reviewed articles published in the English language from inception to June 2022 were retrieved. Methodological quality was established using the modified version of the Downs and Bl...
Uterine extracellular vesicles as multi-signal messengers during maternal recognition of pregnancy in the mare.
Scientific reports    September 16, 2022   Volume 12, Issue 1 15616 doi: 10.1038/s41598-022-19958-z
Rudolf Vegas A, Hamdi M, Podico G, Bollwein H, Fröhlich T, Canisso IF, Bauersachs S, Almiñana C.In contrast to other domestic mammals, the embryo-derived signal(s) leading to maternal recognition of pregnancy (MRP) are still unknow in the mare. We hypothesize that these embryonic signals could be packed into uterine extracellular vesicles (uEVs), acting as multi-signal messengers between the conceptus and the maternal tract, and contributing to MRP. To unveil these signals, the RNA and protein cargos of uEVs isolated from uterine lavages collected from pregnant mares (P; day 10, 11, 12 and 13 after ovulation) and cyclic control mares (C; day 10 and 13 after ovulation) were analyzed. Our ...
Insulin-like growth factor system components expressed at the conceptus-maternal interface during the establishment of equine pregnancy.
Frontiers in veterinary science    September 13, 2022   Volume 9 912721 doi: 10.3389/fvets.2022.912721
Gibson C, de Ruijter-Villani M, Stout TAE.In many species, the insulin-like growth factors (IGF1 and IGF2), their receptors and IGF binding proteins play important roles in preparing the endometrium for implantation, and regulating conceptus growth and development. To determine whether the IGF system may contribute to conceptus-maternal interaction during equine pre-implantation development, we evaluated mRNA expression for IGF system components in conceptuses, and endometrium recovered from pregnant and cycling mares, on days 7, 14, 21 and 28 after ovulation. We also investigated expression of IGF1, IGF2 and their receptors 6 and 11 ...
Endometrial and luteal gene expression of putative gene regulators of the equine maternal recognition of pregnancy.
Animal reproduction science    September 1, 2022   Volume 245 107064 doi: 10.1016/j.anireprosci.2022.107064
Diel de Amorim M, Bramer SA, Rajamanickam GD, Klein C, Card C.Our understanding of the temporal changes in endometrial and luteal gene transcripts related to the actions of oxytocin and prostaglandin during early equine pregnancy is incomplete. Additionally, the role of oxytocinase, also known as Leucyl-cystinyl aminopeptidase (LNPEP), during early pregnancy in mares has not been previously investigated. Luteal and endometrial biopsies were obtained on Day (D)8, D10, D12 and D15 post-ovulation in pregnant (PREG) and diestrus (DIEST) mares for real-time qPCR. Differences in endometrial gene expression occurred over time in: SLC2A4, SLC2A1, PTGES, OXTR and...
Seasonal changes in the expression of molecular markers of stallion germ cells.
Journal of equine veterinary science    August 24, 2022   Volume 118 104109 doi: 10.1016/j.jevs.2022.104109
Shakeel M, Jung H, Yoon D, Yoon M.The economic impacts of infertility and subfertility of stallions greatly influence the horse breeding industry. Self-renewal and differentiation of spermatogonial stem cells are the initial processes to maintain an adequate sperm population. Thus, understanding these processes may provide useful information to reveal the causes and remedies of subfertile and infertile stallions. Stallions are seasonal breeders. About 50% of the sperm population is reduced during the non-breeding season (NBS) in stallions. The seasonal regulation of spermatogenesis renders stallions as ideal models to understa...
Seasonal variation of endogenous adrenocorticotropic hormone concentrations in healthy non-geriatric donkeys in Northern California.
Frontiers in veterinary science    August 12, 2022   Volume 9 981920 doi: 10.3389/fvets.2022.981920
Humphreys S, Kass PH, Magdesian KG, Goodrich E, Berryhill E.Elevated plasma adrenocorticotropic hormone (ACTH) is often used to diagnose pituitary pars intermedia dysfunction (PPID) in horses. The hormone naturally increases in the fall in horses, and donkeys have been found to have higher ACTH concentrations than horses. However, circannual variation of ACTH has not been assessed in donkeys. The objective of the study was to establish seasonal variation of basal plasma ACTH concentrations over the course of a year in clinically healthy, non-geriatric donkeys. It was hypothesized that donkey ACTH concentrations would be higher than those reported in ho...
The effect of priming and duration of oestradiol benzoate treatment before progesterone administration on embryo development and survival in anestrous recipient mares.
Reproduction in domestic animals = Zuchthygiene    August 8, 2022   Volume 57, Issue 11 1474-1477 doi: 10.1111/rda.14220
Oquendo PS, Silva ESM, Oquendo FMG, Cuervo-Arango J, Beletti ME.The effect of three different hormonal protocols to prepare anestrous recipient mares on embryo survival was evaluated. The first group consisted of only progesterone administration (NE) 4 days before embryo transfer, while the recipients from the other two groups received a single administration of 2.5 mg of oestradiol benzoate (SE) 2 days earlier or 8 mg of oestradiol split in increasing doses for 5 consecutive days (LE) ending 3 days before progesterone treatment. The likelihood of recovering an embryo 2 days after transfer was 46.1% (6/13), 62.5% (5/8) and 85.7% (6/7) for recipie...
Effects of Exercise on Donkey Semen Parameters and Some Physiological Indices.
Journal of equine veterinary science    July 16, 2022   Volume 117 104079 doi: 10.1016/j.jevs.2022.104079
Yang F, Wu S, Yang W, Yu J, Liu B, Zeng S.To study the effects of exercise on donkey semen parameters, Dezhou donkey (Equus asinus) jackasses (n = 18) were assigned to three groups: control (CN, n = 6), 1-hour exercise (1 h EX, n = 6) and 2-hour exercise (2 h EX, n = 6) groups. They were exercised with a walking machine for 3 days/week for 8 weeks. Semen parameters and reproductive hormones were evaluated weekly. The heart rate, rectal temperature, blood haematology indexes, and the body condition score (BCS) were also measured. Results showed that the ejaculation volume increased while the sperm concentration decreased after ...
Temporally specific adrenocorticotropic hormone reference intervals for horses in South Africa.
Journal of the South African Veterinary Association    July 12, 2022   Volume 93, Issue 2 116-123 doi: 10.36303/JSAVA.001
Fisher D, Schliewert EC, Hooijberg EH.An endogenous adrenocorticotropic hormone (ACTH) concentration above the reference interval (RI) is commonly used as means for diagnosing equine pituitary pars intermedia dysfunction (PPID). Basal ACTH concentrations are highly dependent on photoperiod and RIs should be month- and location-specific. To date, no ACTH RIs have been specifically established for South Africa. This study aimed to determine geographically and seasonally relevant RIs for equine ACTH in the Gauteng province of South Africa. A longitudinal prospective study was conducted over twelve months to determine ACTH RIs for a r...
Luteal Tissue Area and Immunoreactive Concentration of Progesterone in Plasma of Bred and Non-bred Mares.
Journal of equine veterinary science    July 10, 2022   Volume 118 104075 doi: 10.1016/j.jevs.2022.104075
Colombo I, Podico G, Rudolf-Vegas A, Bauersachs S, Canisso IF.Progesterone is pivotal to maintain pregnancy in the first trimester and low concentration ( .05). Multiple ovulations were associated with greater progesterone concentration and luteal tissue area (P = .0001). There was a moderate positive association between the number of ovulations and luteal tissue area (r = 0.54; P = .0001). The lack of change in the progesterone concentration and luteal tissue area between bred and non-bred mares suggests that horse seminal plasma does not affect luteal function in mares. As all mares had progesterone above 4 ng/mL after 5-days post-ovulation; it i...
The effect of month and breed on plasma adrenocorticotropic hormone concentrations in equids.
Veterinary journal (London, England : 1997)    July 5, 2022   Volume 286 105857 doi: 10.1016/j.tvjl.2022.105857
Durham AE, Potier JF, Huber L.Use of plasma adrenocorticotropic hormone (ACTH) concentrations for the diagnosis of PPID in equids requires awareness of other factors that might influence ACTH concentrations, including breed and time of year. This study was designed to investigate effects of breed on plasma ACTH concentrations and potential interactions between breed and time of year. Ten breeds were selected from a laboratory database containing data on plasma ACTH concentrations. Breeds represented were Arabians, Cobs, Connemara ponies, donkeys, Irish Sports horses, New Forest ponies, Shetland ponies, Thoroughbreds, Warmb...
Molecular Mechanism of Equine Endometrosis: The NF-κB-Dependent Pathway Underlies the Ovarian Steroid Receptors’ Dysfunction.
International journal of molecular sciences    July 1, 2022   Volume 23, Issue 13 7360 doi: 10.3390/ijms23137360
Jasiński T, Zdrojkowski Ł, Ferreira-Dias G, Kautz E, Juszczuk-Kubiak E, Domino M.Endometrosis is a frequently occurring disease decreasing mares' fertility. Thus, it is an important disease of the endometrium associated with epithelial and stromal cell alterations, endometrium gland degeneration and periglandular fibrosis. Multiple degenerative changes are found in uterine mucosa, the endometrium. However, their pathogenesis is not well known. It is thought that nuclear factor-κB (NF-κB), a cell metabolism regulator, and its activation pathways take part in it. The transcription of the profibrotic pathway genes of the NF-κB in fibrotic endometria differed between the fo...
The Kisspeptin analogue C6 induces ovulation in jennies.
Theriogenology    June 15, 2022   Volume 189 107-112 doi: 10.1016/j.theriogenology.2022.06.014
Fanelli D, Beltramo M, Conte G, Cerretini B, Lomet D, Rota A, Aucagne V, Camillo F, Panzani D.Kisspeptins (KPs) are the most potent stimulating neurotransmitters of GnRH release, and consequently KP administration triggers LH and/or FSH release. In small ruminants, KP or its analogs induced an LH surge followed by ovulation in both cyclic and acyclic animals, while in the mare KP only increased LH plasma levels but failed to induce ovulation. This study in jennies compares the endocrinological effects, ovulatory and pregnancy rates of the KP analog C6 and the GnRH analog buserelin acetate. The ovarian activity of nine Amiata jennies was monitored daily by transrectal ultrasound for thr...
The effect of embryo reduction and transfer on luteostasis in the mare.
Animal reproduction science    May 17, 2022   Volume 242 107002 doi: 10.1016/j.anireprosci.2022.107002
This study investigated the effects of embryo reduction and transfer of Day 11 embryos, with or without subsequent reduction, on luteostasis in the mare. In Experiment 1, reduction of embryos at Days 10 (n = 15), 11 (n = 47), 12 (n = 36), 13 (n = 27), 14 (n = 5) and 16 (n = 2) of pregnancy resulted in luteostasis in 13%, 47%, 78%, 89%, 80% and 100% mares. Mares undergoing > 1 embryo reduction showed consistency in when luteostasis occurred. In Experiment 2, transfer of Day 11 embryos to recipient mares 10 (n = 9), 11 (n = 8), 12 (n = 9) and 13 (n = 8) days post ovulatio...
Cortisol Concentration in Horsehair and its Relationship to Body Location, Coat Colour, and Gender.
Journal of equine veterinary science    May 13, 2022   Volume 115 104010 doi: 10.1016/j.jevs.2022.104010
Lelláková M, Lešková L, Florián M, Mesarčová L, Skurková L, Peťková B, Takáčová D, Kottferová J.The determination of cortisol concentrations in animal hair appears to be a relatively simple and non-invasive method of assessing chronic stress. This method has advantages but it also has some drawbacks. We discovered that there are specific coat properties and individual factors in animlas that can affect corisol levels and skew the interpretation of results. We removed horsehair from 8 different areas of the body (chest, left saddle, right saddle, right thoracic fetlock, and left thoracic fetlock, the mane was also sampled at the withers, just behind the ears, and the tail strand) in 31 ho...
Effects of an anti-gonadoliberin releasing hormone vaccine on testicular, epididymal and spermatogenic development in the horse.
Reproduction in domestic animals = Zuchthygiene    May 12, 2022   Volume 57, Issue 8 919-927 doi: 10.1111/rda.14141
Botha AE, Schulman ML, Birrell J, du Plessis L, Laver PN, Soley J, Colenbrander B, Bertschinger HJ.The effects of the GnRH vaccine Improvac on testicular and epididymal morphometrics, histology and spermatogenesis were measured in 19 young (15-20 months) colts randomly assigned to one control (saline, castration at 57 days, n = 6) or either of two GnRH vaccine-treatment groups, T-57 (castration at 57 days, n = 7) or T-100 (castration at 100 days, n = 6), respectively. All were immunized on Day 0 with a single booster on Day 28. Excised testes and epididymides were weighed and processed for histology to measure tubule, epithelial and muscle dimensions, the ratio of interstitial tis...
Emergence and selection of the dominant follicle and gonadotropin dynamics in postpartum lactating versus non-postpartum cycling mares.
Reproductive biology    May 10, 2022   Volume 22, Issue 2 100618 doi: 10.1016/j.repbio.2022.100618
Pastorello M, Gastal MO, Godoi DB, Gastal EL.Among female livestock, the mare has the shortest interval from parturition to first ovulation. Due to the scarcity of research on postpartum mares, little progress has been made on the characterization of the resumption of ovarian cyclicity after parturition. This study compared follicular and gonadotropin dynamics during follicle emergence and deviation in postpartum lactating (PP Lactating) versus non-postpartum cycling (N-PP Cycling) mares. On the day of parturition, every PP Lactating mare was paired with a N-PP Cycling mare. Comparisons were made by considering the partum-ovulation inter...
Suppression of reproductive behaviour and gonadal function in female horses-An update.
Reproduction in domestic animals = Zuchthygiene    May 1, 2022   Volume 57 Suppl 4, Issue Suppl 4 4-12 doi: 10.1111/rda.14129
Aurich C, Kaps M.The behaviour of mares is often detrimental to their performance resulting in frequent demand for methods to suppress gonadal function. In addition, prevention of unintended reproduction especially in feral horse populations may require methods for suppression of gonadal function. Surgical ovariectomy is a safe method but not an acceptable approach in feral mares and undesired in mares where future breeding is considered. There are different approaches for artificial prolongation of the luteal phase resulting in transient inhibition of oestrus and ovulation. Among those, treatment with natural...
The effect of pergolide mesylate on adrenocorticotrophic hormone responses to exogenous thyrotropin releasing hormone in horses.
Veterinary journal (London, England : 1997)    April 25, 2022   Volume 285 105831 doi: 10.1016/j.tvjl.2022.105831
Durham AE.Thyrotropin releasing hormone (TRH) stimulation testing is often used to support a diagnosis of pituitary pars intermedia dysfunction (PPID) in horses although it is unclear whether or not repeat TRH stimulation testing post-treatment is a valid means of assessing response to medical therapy. Laboratory submissions from 64 suspected equine PPID cases were examined including the initial pre-treatment TRH stimulation test and a follow up test within 100 days of starting medical therapy with pergolide. In a subset of cases, further follow-up tests were examined beyond 100 days of starting treatme...
Effect of short-term artificial light and transvaginal progesterone device on first ovulation in late transitional mares.
Journal of equine science    April 19, 2022   Volume 33, Issue 1 1-6 doi: 10.1294/jes.33.1
Bianchi CP, Bruno S, Videla Dorna I, Rodríguez E, Aba MA.In study I, plasma progesterone concentrations were evaluated in anoestrous mares that received an intravaginal progesterone release device (IPRD) for 10 days. Mares were divided into 3 groups based on the dosage of progesterone (0 g, n=3; 1.38 g, n=5; and 1.9 g, n=5). No statistical differences were found in plasma progesterone concentrations between the two doses tested. In study II, the effects of a protocol based on a short program of artificial light combined with an IPRD containing 1.38 g of progesterone on oestrous behaviour and onset of ovulation were evaluated. IPRDs were inserted int...
Serum Cortisol and Its Correlation with Leucocyte Profile and Circulating Lipids in Donkeys (Equus asinus).
Animals : an open access journal from MDPI    March 26, 2022   Volume 12, Issue 7 841 doi: 10.3390/ani12070841
Alberghina D, Statelli A, Monteverde V, Vazzana I, Cascone G, Panzera M.The values for basal serum cortisol concentrations of horses are available in many studies. However, there are limited data about serum cortisol in donkeys. The present study aimed to determine the baseline values for serum cortisol, to evaluate the influence of age and pregnancy on its levels, and to correlate its values with leucocyte profile, serum cholesterol, and triglycerides. Serum samples were collected from 97 healthy donkeys. Cortisol was analyzed by chemo-luminescent assay. The median and the 2.5th and 97.5th percentiles of serum cortisol measured and calculated in all donkeys were ...
Altrenogest treatment reduces the stress response of three-year-old warmblood mares during their initial equestrian training.
Domestic animal endocrinology    March 20, 2022   Volume 80 106728 doi: 10.1016/j.domaniend.2022.106728
Kaps M, Lutzer A, Gautier C, Nagel C, Aurich J, Aurich C.Horse mares are frequently treated with the progestin altrenogest with the aim to suppress estrous behavior and its negative impact on equestrian performance. Progestogens, however, also have sedative effects in males, and females of different species. The aim of our study was therefore to investigate altrenogest-induced changes in the stress response of female horses during initial equestrian training. Three-yr-old Warmblood mares were randomly assigned to treatment with altrenogest (ALT; 0.044 mg/kg once daily; n = 6) or sunflower oil (CON; n = 5) for 12 wk during training. At predefined...
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