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Topic:Fertility

Fertility in horses encompasses the physiological processes and factors influencing reproductive success in equine species. It involves the study of reproductive anatomy, endocrinology, and behavior, as well as the management practices that affect breeding outcomes. Key aspects include the estrous cycle, conception rates, and factors impacting stallion and mare fertility. Reproductive technologies such as artificial insemination, embryo transfer, and hormonal therapies are also explored to enhance breeding efficiency. This page compiles peer-reviewed research studies and scholarly articles that examine the biological mechanisms, management strategies, and technological advancements related to equine fertility.
The role of leptospirosis in reproductive disorders in horses.
Tropical animal health and production    August 30, 2013   Volume 46, Issue 1 1-10 doi: 10.1007/s11250-013-0459-3
Hamond C, Pinna A, Martins G, Lilenbaum W.Leptospirosis is a zoonotic disease of global importance and has a worldwide distribution. This infection displays clear seasonal nature in some regions of the tropics, where the rainy season is marked by high temperatures. Household and wild animals carry leptospires and contribute to their dissemination in nature. Transmission mainly occurs by contact with water contaminated with the urine of infected animals, and consequently, it is quite widespread especially in times of rain, since many areas are subject to flooding and have poor sanitation. Serological tests demonstrate that Leptospira s...
Equine endometrial cytology and bacteriology: effectiveness for predicting live foaling rates.
Veterinary journal (London, England : 1997)    August 11, 2013   Volume 198, Issue 1 206-211 doi: 10.1016/j.tvjl.2013.08.002
Davies Morel MC, Lawlor O, Nash DM.Endometritis is an important cause of sub-fertility in mares. The critical indicator of reproductive success and financial return for commercial studs is live foaling rate. Endometrial bacteriology and/or cytology are used to diagnose endometritis and thus identify mares at risk of early embryonic death. However, mares with endometritis may conceive but then abort in late gestation. The aims of this study were to establish, as part of a standard breeding examination (1) whether a threshold percentage of uterine polymorphonuclear neutrophils (PMNs) exists above which a significant reduction in ...
Biochemical characterization of stallion prostasomes and comparison to their human counterparts.
Systems biology in reproductive medicine    August 2, 2013   Volume 59, Issue 6 297-303 doi: 10.3109/19396368.2013.822612
Ronquist GK, Ek B, Ronquist G, Morrell J, Carlsson L, Larsson A.Release of nanometer-sized prostasomes into human and equine semen suggests essential functions in their relationships with sperm cells and the fertilization process. The two types of prostasomes displayed ultrastructural similarities, albeit the human prostasomes were somewhat larger than the stallion prostasomes. A high ratio of saturated fatty acids was characteristic for the two prostasome types. Electrophoretic separation systems revealed an equine prostasomal pattern different from that of human. The 21 distinctive low molecular weight protein spots in the 2D-gel (with no counterparts in...
Involvement of miRNAs in equine follicle development.
Reproduction (Cambridge, England)    July 31, 2013   Volume 146, Issue 3 273-282 doi: 10.1530/REP-13-0107
Schauer SN, Sontakke SD, Watson ED, Esteves CL, Donadeu FX.Previous evidence from in vitro studies suggests specific roles for a subset of miRNAs, including miR-21, miR-23a, miR-145, miR-503, miR-224, miR-383, miR-378, miR-132, and miR-212, in regulating ovarian follicle development. The objective of this study was to determine changes in the levels of these miRNAs in relation to follicle selection, maturation, and ovulation in the monovular equine ovary. In Experiment 1, follicular fluid was aspirated during ovulatory cycles from the dominant (DO) and largest subordinate (S) follicles of an ovulatory wave and the dominant (DA) follicle of a mid-cycle...
Effect of sex sorting on stallion spermatozoa: Heterologous oocyte binding, tyrosine phosphorylation and acrosome reaction assay.
Animal reproduction science    July 26, 2013   Volume 141, Issue 1-2 68-74 doi: 10.1016/j.anireprosci.2013.07.008
Balao da Silva CM, Spinaci M, Bucci D, Giaretta E, Peña FJ, Mari G, Galeati G.The interest on sex sorting by flow cytometry on the equine industry has been increasing over the years. In this work, three different tests were performed in order to evaluate the membrane status of sorted stallion spermatozoa: assessment of binding ability to porcine oocytes, evaluation of acrosome integrity after stimulation with A23187, and detection of tyrosine phosphorylation. These evaluations were made after incubation for 0h, 1.5h and 3h in a capacitating medium. Sorted stallion spermatozoa attached similarly to the porcine oocytes, when compared with control samples. Sorted spermatoz...
Trypan blue/giemsa staining to assess sperm membrane integrity in salernitano stallions and its relationship to pregnancy rates.
Reproduction in domestic animals = Zuchthygiene    July 24, 2013   Volume 49, Issue 1 41-47 doi: 10.1111/rda.12221
Serafini R, Longobardi V, Spadetta M, Neri D, Ariota B, Gasparrini B, Di Palo R.Aim of this study was to test the reliability of Trypan blue/Giemsa staining to evaluate sperm membrane integrity, acrosomal intactness and morphology in stallion to verify whether it could be applied in vitro as useful tool for sperm fertilizing ability. Fertility data on inseminated mares were collected to evaluate the relationship of sperm quality to pregnancy rates. Forty-one ejaculates were collected from 3 stallions of Salernitano Horse Breed and evaluated for gross appearance, volume, visual motility and membrane integrity with Trypan blue/Giemsa staining and thirty-five mares were inse...
Foaling rates after surgical repair of ventral cervical lacerations using a Trendelenburg position in 18 anesthetized mares.
Veterinary surgery : VS    July 22, 2013   Volume 42, Issue 6 716-720 doi: 10.1111/j.1532-950X.2013.12037.x
Leary JM, Rodgerson D, Spirito M, Gomez J.To (1) describe a surgical technique for repair of lacerations of the ventral aspect of the cervix in anesthetized mares in Trendelenburg position; and (2) report conception rates and foaling after repair. Methods: Case series. Methods: Mares (n = 18). Methods: Cervical lacerations were repaired in 2 layers with anesthetized mares in Trendelenburg position. The cervix was retracted caudally with stay-sutures, and after excision of the healed margin of the laceration, the internal cervical mucosa and fibromuscular tissue were sutured in 1 layer with a continuous Lembert pattern. The externa...
Time of foaling in Arabian mares raised in Tiaret, Algeria.
Asian Pacific journal of tropical biomedicine    July 10, 2013   Volume 3, Issue 7 587-588 doi: 10.1016/S2221-1691(13)60120-3
Meliani S, Benallou B, Halbouche M, Haddouche Z.To enhance effectiveness of reproduction management in Arabian mares, factors influencing the time of foaling were investigated in this study. Methods: Data were collected at the National Haras of Tiaret in Algeria from 2003 to 2010. The foaling time of 255 Arabian pure bred mares, aged from 3 to 20 years were used for this study. Results: A total of 78.07% of foaling happens between 7 pm and 6 am. Conclusions: The influence of the month of foaling and the sex of the foal, on the time of foaling was statically significant.
Cushioned versus noncushioned centrifugation: sperm recovery rate and integrity.
Theriogenology    July 9, 2013   Volume 80, Issue 6 648-653 doi: 10.1016/j.theriogenology.2013.06.009
Len JA, Beehan DP, Lyle SK, Eilts BE.It was hypothesized that optimal sperm recovery rate (RR) without damage to the sperm would be obtained after centrifugation without a cushion solution. Semen collected three times from six light breed stallions was extended to 25 × 10(6) sperm/mL and centrifuged at CON (noncentrifuged), 900NC (no-cushion), 900C (cushion), 1800NC, and 1800C × g for 10 minutes. Sperm concentration, motility (TM and PM), and intact plasma membranes (PLM) and acrosomes (ACR) pre- and postcentrifugation (D0) and after 24 hours (D1) of cooling were evaluated. The RR in the CON (100 ± 0.0), 900NC (93.7 ± 2.9), a...
Relationship between the Placental Retention Time and the Reproductive Performance at the Foal Heat in Thoroughbred and a Comparison with Heavy Draft.
Journal of equine science    June 28, 2013   Volume 24, Issue 2 25-29 doi: 10.1294/jes.24.25
Ishii M, Aoki T, Yamakawa K, Magata F, Gojo C, Ito K, Kayano M, Nambo Y.The aim of this study was to clarify the relationship between the placental retention time (PRT) and the reproductive performance following mating at the foal heat in Thoroughbreds. For this purpose, we interviewed 292 farmers over a period of 3 years with questionnaires evaluating foaling, expulsion of placenta and reproductive performance at the foal heat in 1,432 mares. The obtained data were later compared with a previous study of heavy draft mares. The average of the PRT of the 1,432 Thoroughbred mares was 58 ± 88 min (mean ± SD). The mean PRT of Thoroughbreds was significantly shorter ...
Influence of equine growth hormone, insulin-like growth factor-I and its interaction with gonadotropins on in vitro maturation and cytoskeleton morphology in equine oocytes.
Animal : an international journal of animal bioscience    June 21, 2013   Volume 7, Issue 9 1493-1499 doi: 10.1017/S175173111300116X
Pereira GR, Lorenzo PL, Carneiro GF, Ball BA, Pegoraro LM, Pimentel CA, Liu IK.In horses, successful in vitro fertilization procedures are limited by our inability to consistently mature equine oocytes by in vitro methods. Growth hormone (GH) is an important regulator of female reproduction in mammals, playing an important role in ovarian function, follicular growth and steroidogenesis. The objectives of this research were to investigate: the effects of equine growth hormone (eGH) and insulin-like growth factor-I (IGF-I) on the in vitro maturation (IVM) of equine oocytes, and the effects of eGH in addition to estradiol (E2), gonadotropins (FSH and LH) and fetal calf seru...
[Factors affecting pregnancy rates in the German Thoroughbred Breed].
Tierarztliche Praxis. Ausgabe G, Grosstiere/Nutztiere    June 15, 2013   Volume 41, Issue 3 147-152 
Ewert M, Böröcz J, Uphaus H, Oldenhof H, Distl O, Sieme H.The aim of this study was to evaluate factors affecting pregnancy rates in the German Thoroughbred Breed with particular emphasis on optimisation of fertility rates for breeding stallions of older ages. Methods: Data from the studbooks of the German Thoroughbred Breeding Association from 1996 to 2009 analysed. This analysis included the records of 319 stallions and 6622 brood mares, resulting in 21,372 pregnancies at the end of the season. Results: Pregnancy rates were significantly affected by the age of the stallion and mare as well as the season (month in the breeding season in which coveri...
Induction of ovulation in seasonally anestrous mares under ambient lights using recombinant equine FSH (reFSH).
Theriogenology    June 13, 2013   Volume 80, Issue 5 456-462 doi: 10.1016/j.theriogenology.2013.04.029
Meyers-Brown GA, McCue PM, Troedsson MH, Klein C, Zent W, Ferris RA, Lindholm AR, Scofield DB, Claes AN, Morganti M, Colgin MA, Wetzel RL, Peters AR....Traditionally, mares are put under artificial lights to advance the first ovulation of the year. The aim of the present study was to determine the efficacy of recombinant equine FSH (reFSH) in stimulating follicular development and advancing the first ovulation of the year in seasonally anestrous mares compared with anestrous mares given a placebo. Both groups of mares were housed under ambient light conditions. Sixty deep anestrous mares of light horse breeds (follicular diameters ≤ 20 mm in diameter and progesterone <1 ng/mL) were maintained under a natural photoperiod at three differen...
Focal adhesion kinases and calcium/calmodulin-dependent protein kinases regulate protein tyrosine phosphorylation in stallion sperm.
Biology of reproduction    June 6, 2013   Volume 88, Issue 6 138 doi: 10.1095/biolreprod.112.107078
González-Fernández L, Macías-García B, Loux SC, Varner DD, Hinrichs K.Protein tyrosine phosphorylation (PY) is a hallmark of sperm capacitation. In stallion sperm, calcium inhibits PY at pH 7.8). These results show for the first time a role for calcium/calmodulin-dependent kinases in PRKA-dependent sperm PY; a non-PRKA-dependent pathway regulating sperm PY; and the apparent involvement of the FAK family of protein tyrosine kinases downstream in both pathways.
Region-specific expression of aquaporin subtypes in equine testis, epididymis, and ductus deferens.
Anatomical record (Hoboken, N.J. : 2007)    May 27, 2013   Volume 296, Issue 7 1115-1126 doi: 10.1002/ar.22709
Klein C, Troedsson MH, Rutllant J.The process of water movement in the excurrent duct system of the male reproductive tract is pivotal for establishment of male fertility. The objective was to elucidate expression of aquaporin (AQP) water channels in the stallion reproductive tract. Real-time RT-PCR detected expression of AQP0-5 and AQP7-11 in testis, epididymis, and ductus deferens of mature stallions. There were two main expression patterns: (1) higher expression in testis than in epididymis and ductus deferens (AQP0, -4, -5, -8, -10, and -11); and (2) lower expression in testis than in epididymis and ductus deferens (AQP1, ...
Reactive oxygen species in stallion semen can be affected by season and colloid centrifugation.
Animal reproduction science    May 18, 2013   Volume 140, Issue 1-2 62-69 doi: 10.1016/j.anireprosci.2013.05.006
Morrell JM, Winblad C, Georgakas A, Stuhtmann G, Humblot P, Johannisson A.There are anecdotal reports that equine fertility may decline towards the end of the breeding season. Previous studies have examined differences in sperm quality between the breeding season and non-breeding season but few studies have investigated the proportions of superoxide or peroxide containing spermatozoa at different times during the breeding season. The purpose of this study was to measure the content of these reactive oxygen species (ROS) at the beginning and end of the Swedish breeding season, using flow cytometric analysis of the fluorescence produced after staining with hydroethidi...
Relationships between intrauterine infusion of N-acetylcysteine, equine endometrial pathology, neutrophil function, post-breeding therapy, and reproductive performance.
Theriogenology    April 25, 2013   Volume 80, Issue 3 218-227 doi: 10.1016/j.theriogenology.2013.03.026
Gores-Lindholm AR, LeBlanc MM, Causey R, Hitchborn A, Fayrer-Hosken RA, Kruger M, Vandenplas ML, Flores P, Ahlschwede S.Persistent endometritis in the mare is associated with hypersecretion of mucus by endometrial epithelium and migration of neutrophils into the uterine lumen. This study examines the relationships between N-acetylcysteine (NAC), a mucolytic agent with anti-inflammatory properties, and endometrial architecture, serum neutrophil function, post-breeding therapy, and reproductive performance of NAC-treated mares in a clinical setting. In study 1, endometrial biopsies from mares receiving intrauterine saline (fertile-control, n = 6) or 3.3% NAC (fertile-treatment, n = 6; barren-treatment, n = 10) we...
Factors affecting live foal rates of Thoroughbred mares that undergo manual twin elimination.
Equine veterinary journal    April 24, 2013   Volume 45, Issue 6 676-680 doi: 10.1111/evj.12074
Schnobrich MR, Riddle WT, Stromberg AJ, LeBlanc MM.Mares diagnosed with twin vesicles at 13-17 days after ovulation commonly have one of 2 vesicles manually reduced. It is not known whether vesicle location (adjacent vs. nonadjacent), mare age, mare reproductive status, parity, month of breeding or mare plasma progesterone concentration affects live foal rates. Objective: To determine factors associated with a positive outcome (live foal) in mares undergoing manual twin reduction between 13 and 17 days post ovulation when performed by a single operator. Methods: Retrospective case-control study. Methods: Breeding records and the Jockey Club re...
Pre-selection by double layer density gradient centrifugation improves the fertilising capacity of frozen-thawed, capacitated stallion sperm.
Animal reproduction science    April 18, 2013   Volume 139, Issue 1-4 62-68 doi: 10.1016/j.anireprosci.2013.04.005
Morató R, Soares JM, Orero G, Mogas T, Miró J.The effect of combining double layer density gradient centrifugation (DL-DGC) with different capacitation treatments on the fertilising capacity of frozen-thawed stallion sperm was examined via a heterologous assay involving in vitro-matured, zona pellucida-free bovine oocytes. In a first experiment, aliquots of frozen-thawed stallion sperm were subjected to one of five capacitation treatments without DL-DGC - ionomycin at 1.0μM, 0.1μM, 0.05μM or 0.01μM, or caffeine at 200μg/mL. The fertilising capacity of the semen was then assessed at 18h by staining the above oocytes with 4,6-diamidino...
Sperm trajectories form chiral ribbons.
Scientific reports    April 17, 2013   Volume 3 1664 doi: 10.1038/srep01664
Su TW, Choi I, Feng J, Huang K, McLeod E, Ozcan A.We report the discovery of an entirely new three-dimensional (3D) swimming pattern observed in human and horse sperms. This motion is in the form of 'chiral ribbons', where the planar swing of the sperm head occurs on an osculating plane creating in some cases a helical ribbon and in some others a twisted ribbon. The latter, i.e., the twisted ribbon trajectory, also defines a minimal surface, exhibiting zero mean curvature for all the points on its surface. These chiral ribbon swimming patterns cannot be represented or understood by already known patterns of sperms or other micro-swimmers. The...
The absence of ER-β results in altered gene expression in ovarian granulosa cells isolated from in vivo preovulatory follicles.
Endocrinology    April 11, 2013   Volume 154, Issue 6 2174-2187 doi: 10.1210/en.2012-2256
Binder AK, Rodriguez KF, Hamilton KJ, Stockton PS, Reed CE, Korach KS.Determining the spatial and temporal expression of genes involved in the ovulatory pathway is critical for the understanding of the role of each estrogen receptor in the modulation of folliculogenesis and ovulation. Estrogen receptor (ER)-β is highly expressed in ovarian granulosa cells, and mice lacking ER-β are subfertile due to inefficient ovulation. Previous work has focused on isolated granulosa cells or cultured follicles and, although informative, provides confounding results due to the heterogeneous cell types present including granulosa and theca cells and oocytes and exposure to in...
Reply to Andy Durham.
Equine veterinary journal    April 10, 2013   Volume 45, Issue 3 388-389 doi: 10.1111/evj.12073
Suthers J, Proudman C, Pinchbeck G, Archer D.No abstract available
New seminal plasma removal method for freezing stallion semen.
Theriogenology    April 9, 2013   Volume 79, Issue 7 1120-1123.e1 doi: 10.1016/j.theriogenology.2013.01.014
Ramires Neto C, Monteiro GA, Soares RF, Pedrazzi C, Dell'aqua JA, Papa FO, Castro-Chaves MM, Alvarenga MA.Seminal plasma removal, an indispensable step in equine semen cryopreservation, is usually done by centrifugation, but this might cause mechanical damage to sperm. A new method for seminal plasma removal from stallion semen, namely a filter composed of a synthetic hydrophilic membrane (Sperm Filter, BotuPharma, Botucatu, Sao Paulo, Brazil), was recently proposed. The objective of this study was to test the use of the Sperm Filter in the removal of seminal plasma before freezing stallion semen. Ejaculates from 31 stallions were divided into two groups and cryopreserved. In group 1 (G1), seminal...
The effects of kisspeptin on gonadotropin release in non-human mammals.
Advances in experimental medicine and biology    April 4, 2013   Volume 784 63-87 doi: 10.1007/978-1-4614-6199-9_4
Abbara A, Ratnasabapathy R, Jayasena CN, Dhillo WS.The Kiss1 gene encodes a 145-amino acid pre-peptide, kisspeptin, which is cleaved into smaller peptides of 54, 14, 13, and 10 amino acids. This chapter reviews in detail the effects of kisspeptin on gonadotropin secretion in non-human mammals. Studies of kisspeptin's effects have included both acute and chronic administration regimens via a number of administration routes. Acute kisspeptin stimulates gonadotropin secretion in a wide range of species of non-human mammals, including rats, mice, hamsters, sheep, pigs, goats, cows, horses, and monkeys. In general, the stimulatory effect of kisspep...
Development of the genital microflora in stallions used for artificial insemination throughout the breeding season.
Animal reproduction science    March 29, 2013   Volume 139, Issue 1-4 53-61 doi: 10.1016/j.anireprosci.2013.03.009
Pasing SS, Aurich C, von Lewinski M, Wulf M, Krüger M, Aurich JE.An important factor influencing stallion fertility is the microbial contamination of semen. Aims of this study were to investigate changes in the microbiological population of the genital mucosa and semen in artificial insemination stallions (n=16) from before to after one breeding season (February-August). MALDI-TOF-MS (matrix assisted laser desorption/ionization time-of-flight mass spectrometry) was used for identification of microbial agents. For bacteriology, swabs from the urethral opening, urethral fossa and penile sheath as well as semen were collected at 4-week-intervals. For semen mot...
Kisspeptin as a master player in the central control of reproduction in mammals: an overview of kisspeptin research in domestic animals.
Animal science journal = Nihon chikusan Gakkaiho    March 27, 2013   Volume 84, Issue 5 369-381 doi: 10.1111/asj.12056
Okamura H, Yamamura T, Wakabayashi Y.The hypothalamo-pituitary-gonadal (HPG) axis is the regulatory system for reproduction in mammals. Because secretion of gonadotropin-releasing hormone (GnRH) into the portal vessels is the final step at which the brain controls gonadal activities, the GnRH neuronal system had been thought to be central to the HPG axis. A newly discovered neural peptide, kisspeptin, has opened a new era in reproductive neuroendocrinology. As shown in a variety of mammals, kisspeptin is a potent endogenous secretagogue of GnRH, and the kisspeptin neuronal system governs both the pulsatile GnRH secretion that dri...
Assessment of extent of apoptosis and DNA defragmentation in chilled semen of stallions during the breeding season.
Reproduction in domestic animals = Zuchthygiene    March 26, 2013   Volume 48, Issue 5 826-832 doi: 10.1111/rda.12170
Krakowski L, Obara J, Wąchocka A, Piech T, Bartoszek P, Kostro K, Tatara MR.The objective of the study was to assess apoptosis and DNA defragmentation in equine semen diluted and chilled to +4°C. Semen was collected from nine fertile stallions, including four Arabian thoroughbreds and five coldbloods. Examinations were carried out immediately after semen collection (0) and at five storage times (24, 48, 72, 96 and 120 h). The basic semen evaluation was performed in terms of volume, sperm concentration, viable sperm percentage, progressive motility and morphology. Using flow cytometry, DNA defragmentation and cell membrane integrity of spermatozoa were determined. Th...
Sex sorting increases the permeability of the membrane of stallion spermatozoa.
Animal reproduction science    March 14, 2013   Volume 138, Issue 3-4 241-251 doi: 10.1016/j.anireprosci.2013.02.021
Balao da Silva CM, Ortega Ferrusola C, Morillo Rodriguez A, Gallardo Bolaños JM, Plaza Dávila M, Morrell JM, Rodriguez Martínez H, Tapia JA....At present, the only repeatable means of selecting the sex of offspring is the Beltsville semen sorting technology using flow cytometry (FC). This technology has reached commercial status in the bovine industry and substantial advances have occurred recently in swine and ovine species. In the equine species, however, the technology is not as well developed. To better understand the changes induced in stallion spermatozoa during the sorting procedure, pooled sperm samples were sorted: sperm motility and kinematics were assessed using computer assisted sperm analysis, sperm membrane integrity wa...
Growth rate of ovulatory follicles during the first ovulatory oestrus (after seasonal anoestrus) and subsequent oestrous period in Irish Draught mares.
Irish veterinary journal    March 12, 2013   Volume 66, Issue 1 4 doi: 10.1186/2046-0481-66-4
Newcombe JR, Cuervo-Arango J.It is believed that during the spring transition, the developing follicle tends to grow more slowly, persist longer and grow to a larger diameter prior to ovulation than at subsequent oestrus periods. A general suspicion, that the first ovulation of the year is less fertile than subsequent ovulations could be explained by a slower growth rate of the ovulatory follicle during transition with the consequent production of a subfertile oocyte. By detailed serial examination of the same group of Irish Draught mares over three winter/spring periods, no significant difference was found in either grow...
Effect of surgical technique for unilateral orchiectomy on subsequent testicular function in Miniature Horse stallions.
Equine veterinary journal. Supplement    March 2, 2013   Issue 43 100-104 doi: 10.1111/j.2042-3306.2012.00639.x
McCormick JD, Valdez R, Rakestraw PC, Varner DD, Blanchard TL, Cavinder CA, Sudderth AK, Kiser A, Love CC.Management decisions on unilateral orchiectomy are often influenced by the potential for post operative return to successful breeding. The effects of 2 surgical methods (first intention [FI] vs. second intention [SI] incision healing) for unilateral orchiectomy on resulting semen quality and scrotal temperature were evaluated. Objective: To evaluate the effects of 2 surgical unilateral orchiectomy techniques on scrotal healing, size of the remaining testis and post operative sperm quality. Methods: Unilateral orchiectomy was performed on mature Miniature Horse stallions. Semen was collected pr...
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