Estrogens are steroid hormones that play a significant role in the reproductive physiology of horses. They are primarily produced by the ovaries, but can also be synthesized in smaller amounts by the adrenal glands and placenta. Estrogens are involved in the regulation of the estrous cycle, influencing reproductive behaviors, and preparing the reproductive tract for potential pregnancy. In mares, the most prominent estrogens include estradiol, estrone, and equilin. These hormones can also impact bone density, cardiovascular function, and metabolism. This page compiles peer-reviewed research studies and scholarly articles that explore the production, function, and clinical implications of estrogens in equine health and reproduction.
Legacki EL, Corbin CJ, Ball BA, Scoggin KE, Stanley SD, Conley AJ.Steroidogenic enzymes in placentas shape steroid hormone profiles in the maternal circulation of each mammalian species. These include 3β-hydroxysteroid dehydrogenase/Δ5-4 isomerase (3βHSD) and 17α-hydroxylase/17,20-lyase cytochrome P450 (P450c17) crucial for progesterone and androgen synthesis, respectively, as well as aromatase cytochrome P450 (P450arom) that converts Δ4-androgens to estrogens. 5α-reductase is another important enzyme in equine placentas because 5α-dihydroprogesterone (DHP) sustains pregnancy in the absence of progesterone in the second half of equine pregnancy. DHP a...
Raeside JI.The role of steroids in human medicine is well recognized, but the major contributions made by the large domestic animals as a source of material in the discovery, isolation, and determination of the structure of the steroid hormones is less well appreciated. After a brief reminder of the early efforts to obtain a reliable source of steroids for clinical use, the narrative here is to outline one example where success was ultimately achieved for estrogen replacement therapy. Whereas knowledge of the high concentrations of estrogens in urine of pregnant women and mares dates from the late 1920s,...
Knutsen HK, Alexander J, Barregård L, Bignami M, Brüschweiler B, Ceccatelli S, Cottrill B, Dinovi M, Edler L, Grasl-Kraupp B, Hogstrand C....Zearalenone (ZEN), a mycotoxin primarily produced by Fusarium fungi, occurs predominantly in cereal grains. The European Commission asked EFSA for a scientific opinion on the risk to animal health related to ZEN and its modified forms in feed. Modified forms of ZEN occurring in feed include phase I metabolites α-zearalenol (α-ZEL), β-zearalenol (β-ZEL), α-zearalanol (α-ZAL), β-zearalanol (β-ZAL), zearalanone (ZAN) and phase II conjugates. ZEN has oestrogenic activity and the oestrogenic activity of the modified forms of ZEN differs considerably. For ZEN, the EFSA Panel on Contaminants...
Zutz C, Wagener K, Yankova D, Eder S, Möstl E, Drillich M, Rychli K, Wagner M, Strauss J.Estrogenic active compounds are present in a variety of sources and may alter biological functions in vertebrates. Therefore, it is crucial to develop innovative analytical systems that allow us to screen a broad spectrum of matrices and deliver fast and reliable results. We present the adaptation and validation of a fungal biosensor for the detection of estrogen activity in cow derived samples and tested the clinical applicability for pregnancy diagnosis in 140 mares and 120 cows. As biosensor we used a previously engineered genetically modified strain of the filamentous fungus Aspergillus ni...
Killisch R, Böttcher D, Theuß T, Edzards H, Martinsson G, Einspanier A, Gottschalk J, Schoon HA.The deep anoestrous phase in winter is part of the anovulatory season in mares and is bordered by the autumn and spring transitional periods (ATP/STP). To define an annual time span for effective prognostic biopsy sampling, the aim of this study was to provide a morphofunctional characterization of the endometrium during ATP and STP. To outline both transitional periods, endometrial specimens were taken in September, October and November (n = 76) as well as February, March and April (n = 184) with the requirement of a detailed clinical documentation. Tissue samples were examined histologic...
Pinto-Bravo P, Galvão A, Rebordão MR, Amaral A, Ramilo D, Silva E, Szóstek-Mioduchowska A, Alexandre-Pires G, Roberto da Costa R, Skarzynski DJ....The oviduct plays important roles in the early reproductive process. The aim of this study was to evaluate gene transcription and protein expression of progesterone receptor (PGR), estrogen receptors 1 (ESR1) and 2 (ESR2); oxytocin receptor (OXTR); prostaglandin F2α synthase (AKR1C3), and prostaglandin E2 synthase (Ptges) in mare oviduct in different estrous cycle stages. Estradiol (E), progesterone (P), oxytocin (OXT), and tumor necrosis factor α (TNF) effect on in vitro PGE and prostaglandin F2α (PGF) secretion by equine oviduct explants or by oviductal epithelial cells (OECs) were also ...
Silva ESM, Ignácio FS, Fritsch SC, Zanoni DS, Pantoja JCF, Oliveira-Filho JP, Meira C.To test the hypothesis that the administration of 2.5 mg of estradiol benzoate (EB) followed by 1500 mg of long acting progesterone (LA P4) causes similar uterine changes and molecular dynamics in anovulatory mares to those observed in cyclic ones, we evaluated the changes of estrogen (ERα and ERβ) and progesterone receptors (PR) in anestrous, transitional and cyclic mares by RT-qPCR and immunohistochemistry. In addition, we evaluated uterine edema, tonus and estrogens and progesterone plasma profile. Endometrial biopsies were taken from anestrous and transitional mares immediately before ...
Shikichi M, Iwata K, Ito K, Miyakoshi D, Murase H, Sato F, Korosue K, Nagata S, Nambo Y.Measurement of progestines and estrogens in maternal plasma has been advocated as an indicator of foeto-placental function. The goals of the present study were as follows: to determine progestin and estrogen concentrations in mares with normal and abnormal pregnancies during late gestation, evaluate the diagnostic value of hormone concentrations, and investigate the relationship between hormone concentrations after treatment and the survival of foals. Blood samples were collected monthly from 459 pregnant mares between Day 201 of gestation and foaling. Progestin and estrogen concentrations wer...
Maldonado PA, Montoya TI, Acevedo JF, Keller PW, Word RA.Although the positive effects of vaginal estrogens and the selective estrogen receptor modulator, ospemifene (OS), on the vaginal epithelium are well recognized, less is known regarding the effects of these therapies on the lower urinary tract or vaginal muscularis. Clinical evidence suggests that vaginally administered estrogen may improve overactive bladder-related symptoms. The objective of this study was to compare the effects of OS, vaginal conjugated equine estrogens (CEE), or both on the vaginal wall and lower urinary tract in a rat model of menopause. Contractile force of the bladder n...
Allen WRT, Stansfield F, Wilsher S.The placenta and fetal gonads of 12 pregnant plains zebra (Equus quagga), estimated to be between 81 and 239 days of gestation, were examined. The diffuse, microcotyledonary zebra placenta appeared, developmentally, to be 3-4 weeks behind its counterpart in horse pregnancy and this, together with the presence of small and long-lived endometrial cups, low levels of zebra chorionic gonadotrophin in maternal serum and few accessory corpora lutea in the maternal ovaries during the first half of gestation, made zebra pregnancy more similar to donkey than horse pregnancy. Zebra fetal gonads enlarged...
Esteller-Vico A, Ball BA, Troedsson MHT, Squires EL.Equine pregnancy is characterized by very high circulating concentrations of estrogens. The physiological roles of estrogens during equine gestation are largely unknown, although some studies suggest a role in the regulation of uterine artery hemodynamics and a relationship between low circulating estrogen concentrations and late pregnancy loss. The objectives of this experiment were to evaluate the effects of estrogen suppression on uterine artery hemodynamics and on pregnancy outcome. Estrogen synthesis was suppressed using letrozole, a potent aromatase inhibitor. Twelve pregnant mares were ...
D'Souza-Anjo M, Christensen BW, Brabender K, Zimmermann W, Kass PH, Schwarzenberger F.The aim of this study was to determine whether concentrations of reproductive steroid hormone metabolites significantly differed between harem stallions and bachelor stallions in the free ranging group of Przewalski's horses (Equus ferus przewalskii) at the Hortobágy National Park in Hungary. Throughout the study, fecal samples were collected from 21 harem stallions and 15 bachelor stallions and analyzed for immunoreactive estrogen and androgen metabolites. Harem stallions demonstrated significantly higher concentrations of estrogen (P < 0.001) and epi-androsterone (P < 0.001), ...
Allen WR, Gower S, Wilsher S.Implantation and placentation in the mare does not commence until as late as day 40 after ovulation. The reasons for this and the growth factors and/or hormones which drive placentation when it does finally occur are of considerable academic and practical interest. Placental interface tissues recovered from 11 accurately aged and perfused-fixed horse uteri between 20 and 68 days of gestation were stained immunocytochemically for Epidermal Growth Factor (EGF), its specific receptor (EGF-R) and for the steroid hormone enzyme, aromatase. EGF was present in endometrial gland and lumenal epithelia ...
Rebordão MR, Galvão A, Pinto-Bravo P, Pinheiro J, Gamboa S, Silva E, Mateus L, Ferreira-Dias G.Oxytocin (OXT) has been used to prolong the luteal phase in mares, but its mechanism of action is unknown. The aim of this study was to evaluate the effect of chronic exogenous OXT administration to mid-luteal phase mares on luteal maintenance. Also, endometrial expression of prostaglandin endoperoxide synthase 2 (PTGS2), prostaglandin Fα, E and I synthases (AKR1C3, PTGES, and PTGIS), oxytocin receptor (OXTR), progesterone receptor (PGR), and estrogen receptors 1 (ESR1) and 2 (ESR2) were assessed in mares experiencing luteal maintenance 2 weeks after chronic exogenous OXT administration. Con...
Gautier C, Barrier-Battut I, Guénon I, Goux D, Delalande C, Bouraïma-Lelong H.Estrogen receptors ESR1, ESR2 and GPER are present on mature ejaculated horse spermatozoa, suggesting these cells as putative targets for estrogens. Indeed, spermatozoa are exposed to high level of estrogens during the transit in the male and female genital tracts but their roles are not investigated. So, we evaluated in vitro the role of 17β-estradiol during post-testicular maturations: regulation of motility, capacitation and acrosome reaction. Moreover according to the pseudo-seasonal breeder status of the stallion, we analyzed the putative seasonal variations in the presence of ESRs in sp...
Klein C."Maternal recognition of pregnancy" (MRP) is commonly used to describe the ongoing embryo-maternal communication during early pregnancy that culminates in prevention of luteolysis and ensures ongoing progestin support. The conceptus-derived pregnancy recognition signal has not yet been identified in the mare. Although equine conceptuses produce substantial amounts of estrogens, there is a lack of evidence that estrogens are the pregnancy recognition signal in mares. Conceptus mobility is integral to MRP and is driven by conceptus-derived prostaglandin production. Cessation of conceptus mobilit...
Canisso IF, Ball BA, Esteller-Vico A, Williams NM, Squires EL, Troedsson MH.While advanced stages of ascending placentitis can be diagnosed by transrectal ultrasonography and clinical signs, early stages can be missed. Thus, additional tools could enhance assessment of placental health. Objective: To characterise peripheral dehydroepiandrosterone sulphate (DHEA-S) and testosterone concentrations in mares carrying normal pregnancies (Study 1) and compare plasma concentrations of DHEA-S, testosterone, oestradiol 17-β (oestradiol) and oestrone sulphate (OES) in mares with or without placentitis (Study 2). Methods: Longitudinal cohort study of healthy mares (Study 1) and...
Martínez-Boví R, Cuervo-Arango J.The objectives were to determine: (i) whether intrafollicular administration of PGE2 and PGF2α to mares would hasten follicle collapse and (ii) the differences in reproductive hormone characteristics in mares with spontaneous and prostaglandin-induced follicle collapses. Six mares were followed for two oestrous cycles each: when the mares reached a follicle diameter of 30-35 mm and showed mild-to-moderate endometrial oedema, mares were administered a single 0.5 ml dose containing 500 μg PGE2 and 125 μg PGF2α (treatment cycle) or a placebo (0.5 ml of water for injection; control cycle) into...
Klein V, Müller K, Schoon HA, Reilas T, Rivera del Alamo MM, Katila T.Oestrous suppression by intrauterine devices (IUDs) is caused by prolongation of luteal function, but the biological mechanism is unknown. The aim of the study was to investigate mechanisms which could explain the action of IUDs. Thirty mares were age-matched and either inseminated (AI, n = 15) or fitted with an IUD (IUD, n = 15) and subsequently divided into four groups: AI-P, pregnant (n = 8); AI-N, non-pregnant (n = 7); IUD-P, prolonged luteal phase (n = 7); and IUD-N, normal luteal phase (n = 8). The median ages were 5.5 and 7 years in AI-P and IUD-P groups and 14 and 11 years in AI-N and ...
Klein C.Few, if any, biological processes are as diverse among domestic species as establishment of early pregnancy, in particular maternal recognition of pregnancy. Following fertilization and initial development in the mare oviduct, selective transport of the embryo through the uterotubal junction driven by embryo-derived PGE2 occurs. Upon arrival in the uterus, an acellular glycoprotein capsule is formed that covers the embryo, blastocyst, and conceptus (embryo and associated extraembryonic membranes) between the second and third weeks of pregnancy. Between Days 9 and 15/16 of pregnancy, the concep...
Herrera-Luna CV, Scarlet D, Walter I, Aurich C.The aim of the present study was to characterise receptors for LH and FSH (LHR and FSHR, respectively) and aromatase in epididymal and testicular tissue from stallions of different ages (prepubertal, young, mature and old). Gene and protein expression were assessed by real-time quantitative polymerase chain reaction (real-time qPCR), immunohistochemistry and multiple immunofluorescence labelling. There were no differences in LHR mRNA expression in epididymal and testicular parenchyma in stallions of different age. In contrast, expression of FSHR and CYP19A1 in caput, corpus and cauda epididymi...
Hughes K, Scase TJ, Foote AK.Equine mammary tumors are uncommon, and relatively sparse histopathologic and molecular data exist. The present study describes the histopathologic features of 7 such tumors, which exhibited infiltrative growth, intermediate to high mitotic rates, and focally extensive necrosis. The tumors exhibited variably strong staining for vimentin and cytokeratin 14, as well as frequently weak cytoplasmic staining for pan-cytokeratin. E-cadherin expression was strong. Interestingly, a subgroup of the tumors exhibited strong nuclear staining for estrogen receptor α. Three of 7 tumors exhibited nuclear ex...
Silva ES, Scoggin KE, Canisso IF, Troedsson MH, Squires EL, Ball BA.The objective of this study was to compare expression of estrogen receptor alpha (ER-α), β (ER-β), progesterone receptor (PR), as well as prostaglandin E2 type 2 (EP2) and 4 (EP4) receptors in the equine myometrium and endometrium during estrus, diestrus and early pregnancy. Tissues were collected during estrus, diestrus, and early pregnancy. Transcripts for ER-α (ESR1), ER-β (ESR2), PR (PGR), EP2 (PTGER2) and EP4 (PTGER4) were quantified by qPCR. Immunohistochemistry was used to localize ER-α, ER-β, PR, EP2 and EP4. Differences in transcript in endometrium and myometrium were compared ...
Collins CW, Monfort SL, Vick MM, Wolfe BA, Weiss RB, Keefer CL, Songsasen N.To date, there has been limited research on manipulation of the estrous cycle in endangered equids. The objectives of this study were to assess the efficacy of using combinations of: (a) oral altrenogest and PGF2α, and (b) injectable altrenogest and PGF2α for manipulation of ovarian activity in Przewalski's mares. Reproductive cycles were monitored by assessing follicular changes with rectal ultrasound and changes in urinary steroid hormones. In Study 1, five cycling mares were treated with oral altrenogest (n=11 cycles) for 14 days. In Study 2, cycling mares were treated with oral altrenoge...
de Ruijter-Villani M, van Tol HT, Stout TA.Endometrial oxytocin receptors (OXTR) and prostaglandin-endoperoxide synthase 2 (PTGS2) are central components of the luteolytic pathway in cyclic mares, and their suppression is thought to be critical to luteal maintenance during early pregnancy. We examined the effect of pregnancy on endometrial expression of potential regulators of prostaglandin (PG) F2α secretion in mares. Expression of the nuclear progesterone receptor and oestrogen receptor ERα was high during oestrus, and depressed when progesterone was elevated; the opposite applied to the membrane progesterone receptor. PTGS2 was up...
Arkoun B, Gautier C, Delalande C, Barrier-Battut I, Guénon I, Goux D, Bouraïma-Lelong H.Among mammals, the stallion produces the largest amount of testicular estrogens. These steroid hormones are produced mainly by Leydig and Sertoli cells in the testis and also in the epididymis. Their role in horse testicular physiology and their ability to act on spermatozoa are still unknown. In order to determine if spermatozoa are targets for estrogens, the presence of estrogen receptors in mature ejaculated spermatozoa has been investigated. The presence of a single isoform of ESR1 (66kDa) and ESR2 (61kDa) was found by Western-blot analysis in samples from seven stallions. Confocal analysi...
Ferreira-Dias G, Botelho M, Zagrajczuk A, Rebordão MR, Galvão AM, Bravo PP, Piotrowska-Tomala K, Szóstek AZ, Wiczkowski W, Piskula M, Fradinho MJ....Phytoestrogens exist in plants that are present in forages fed to horses. They may compete with 17-β estradiol and influence the estrous cycle. Therefore, the objective was to determine whether coumestrol from clover-mixed pastures is present in mare's plasma after their ingestion (experiment I), and when this phytoestrogen was present in mare's plasma after ingestion (experiment II). The effect of a long-term ingestion of phytoestrogens on estrous cycle disruption was assessed (experiment III; clinical case). Experiment I was carried out in nonpregnant anestrous and cyclic Lusitano mares (n ...
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...
Raeside JI, Christie HL, Waelchli RO, Betteridge KJ.The embryo proper in early equine pregnancy has recently been shown to have a remarkable capacity for metabolism of oestrogens. High concentrations of oestrogens in yolk-sac fluid could provide substrate for local metabolism in tissues of the embryo proper and this activity could have significance for early development. Due to the high level of oestrogen metabolism in the embryo proper we examined the possibility that it could also biosynthesise oestrogens. Conceptuses were collected in the fourth week of pregnancy (n=23) and the embryo was separated from extraembryonic tissues for incubation ...
Moeller BC, Stanley SD.A method for the detection and quantitation of 35 endogenous steroids in equine serum was developed and validated. Androgens, estrogens, progestins and their metabolites potentially present in serum were simultaneously monitored in one method using on-line sample extraction by turbulent flow chromatography (TFC) on a 2-dimensional liquid chromatography system and detected on a triple-stage quadrupole mass spectrometer by electrospray ionization. Analytes were detected and quantitated by single-reaction monitoring or selected-ion monitoring. Limits of detection (range 0.025-10 ng mL(-1)) and qu...
Vardy MD, Gardner TR, Cosman F, Scotti RJ, Mikhail MS, Preiss-Bloom AO, Williams JK, Cline JM, Lindsay R.The purpose of this study was to determine effects of ovariectomy (OVX) and conjugated equine estrogens plus medroxyprogesterone acetate (CEE/MPA), or ethinyl estradiol plus norethindrone acetate (EE/NA) on biomechanics of uterosacral (USL) and round (RL) ligaments in postmenopausal (PMP) monkeys. Methods: This was a randomized, triple blind, placebo-controlled study. OVX monkeys received 12 months no treatment (Pbo) (n = 19), CEE/MPA (n = 19), or EE/NA (n = 21). USL and RL step strains and stress-relaxation data were curve-fitted, giving strain-dependent tensile modulus (TM) from 0% to 30%. R...
Klein C, Troedsson MH.Maternal recognition of pregnancy in the horse is the sum of events leading to maintenance of pregnancy; in a narrow sense, maternal recognition of pregnancy refers to the physiological process by which the lifespan of the corpus luteum is prolonged. The horse is one of the few domestic species in which the conceptus-derived pregnancy recognition signal has not been identified. The presence of the conceptus reduces pulsatile prostaglandin F(2α) secretion by the endometrium during early gestation in the mare, partly attributed to the reduced expression of cyclooxygenase-2. Cyclooxygenase-2 has...
Wilsher S, Allen WR.The maternal recognition of pregnancy (MRP) signal in the mare has not been determined, although oestrogens have been proposed as a potential candidate. Objective: To determine effects of intrauterine administration of oestrogen and various oils on cyclic luteolysis in the mare. Objective: Intrauterine oestradiol or fatty acids may suppress luteolysis in the cycling mare when administered during late dioestrus. Methods: A single 1 ml dose of slow-release oestradiol (10 mg/ml) in fractionated coconut oil was infused into the uterine lumen of cycling mares on Days 6, 8, 10, 12 or 14 post ovulati...
Klein C."Maternal recognition of pregnancy" (MRP) is commonly used to describe the ongoing embryo-maternal communication during early pregnancy that culminates in prevention of luteolysis and ensures ongoing progestin support. The conceptus-derived pregnancy recognition signal has not yet been identified in the mare. Although equine conceptuses produce substantial amounts of estrogens, there is a lack of evidence that estrogens are the pregnancy recognition signal in mares. Conceptus mobility is integral to MRP and is driven by conceptus-derived prostaglandin production. Cessation of conceptus mobilit...
Raeside JI.The role of steroids in human medicine is well recognized, but the major contributions made by the large domestic animals as a source of material in the discovery, isolation, and determination of the structure of the steroid hormones is less well appreciated. After a brief reminder of the early efforts to obtain a reliable source of steroids for clinical use, the narrative here is to outline one example where success was ultimately achieved for estrogen replacement therapy. Whereas knowledge of the high concentrations of estrogens in urine of pregnant women and mares dates from the late 1920s,...
Yasui M, Suzuki N, Liu X, Okamoto Y, Kim SY, Laxmi YR, Shibutani S.4-Hydroxyequilenin (4-OHEN)-dC is a major, potentially mutagenic DNA adduct induced by equine estrogens used for hormone replacement therapy. To study the miscoding property of 4-OHEN-dC and the involvement of Y-family human DNA polymerases (pols) eta, kappa and iota in that process, we incorporated 4-OHEN-dC into oligodeoxynucleotides and used them as templates in primer extension reactions catalyzed by pol eta, kappa and iota. Pol eta inserted dAMP opposite 4-OHEN-dC, accompanied by lesser amounts of dCMP and dTMP incorporation and base deletion. Pol kappa promoted base deletions as well as ...
Clarkson TB.Clearly, a new era has begun, with increasing numbers of the scientific/medical community asking whether estrogens have any cardiovascular benefits. Doubts have arisen from two randomized prospective trials. The Heart and Estrogen/progestin Replacement Study (women who were generally beyond 65 years of age with preexisting coronary heart disease) found no benefit in reducing coronary events by a combination of estrogens and a progestin. Later, the Estrogen Replacement Atherosclerosis Trial reported that no benefit could be shown for either conjugated equine estrogens only or the combined thera...
Talboom JS, Engler-Chiurazzi EB, Whiteaker P, Simard AR, Lukas R, Acosta JI, Prokai L, Bimonte-Nelson HA.In women, ovarian hormone loss at menopause has been related to cognitive decline, and some studies suggest that estrogen-containing hormone therapy (HT) can mitigate these effects. Recently, the Women's Health Initiative study found that conjugated equine estrogens, the most commonly prescribed HT, do not benefit cognition. Isolated components of conjugated equine estrogens (tradename Premarin(®)) have been evaluated in vitro, with delta(8,9)-dehydroestrone (∆(8)E1) and equilin showing the strongest neuroprotective profiles. It has not been evaluated whether ∆(8)E1 or equilin impact cogn...
Silva ES, Scoggin KE, Canisso IF, Troedsson MH, Squires EL, Ball BA.The objective of this study was to compare expression of estrogen receptor alpha (ER-α), β (ER-β), progesterone receptor (PR), as well as prostaglandin E2 type 2 (EP2) and 4 (EP4) receptors in the equine myometrium and endometrium during estrus, diestrus and early pregnancy. Tissues were collected during estrus, diestrus, and early pregnancy. Transcripts for ER-α (ESR1), ER-β (ESR2), PR (PGR), EP2 (PTGER2) and EP4 (PTGER4) were quantified by qPCR. Immunohistochemistry was used to localize ER-α, ER-β, PR, EP2 and EP4. Differences in transcript in endometrium and myometrium were compared ...
LeBlanc MM.Ascending placentitis is a common cause of premature birth, abortion and delivery of compromised, ill foals. Recent experimental models have investigated diagnostic procedures and treatment strategies in an attempt to improve live foal rate. Diagnostics such as transrectal and transabdominal ultrasonography are used to evaluate foetal well-being and placental separation, while measurement of plasma progestins or oestrogen identifies a stressed or hypoxic foetus. Treatment is directed at stopping spread of infection, maintaining uterine quiescence and blocking production of pro-inflammatory cyt...
Hess MF, Roser JF.The large amount of testicular estrogens produced by the stallion is unique compared to the amounts found in other domestic species. Although the cellular locale of the cytochrome P450 aromatase (P450arom) enzyme that converts C19 androgens to C18 estrogens has been identified in the Leydig cell of adult equine testis, the location in the immature equine testis is not known. The goal of this work was to localize the enzyme in colts and stallions during sexual development. Testes were obtained from prepubertal (n=7), pubertal (n=6), and postpubertal (n=8) colts and stallions during both the bre...
Almeida J, Conley AJ, Mathewson L, Ball BA.In the mammalian testis, Leydig cells are primarily responsible for steroidogenesis. In adult stallions, the major endocrine products of Leydig cells include testosterone and estrogens. 3β-hydroxysteroid dehydrogenase/Δ(5)-Δ(4)-isomerase (3βHSD) and 17α-hydroxylase/17,20-lyase (P450c17) are two key steroidogenic enzymes that regulate testosterone synthesis. Androgens produced by P450c17 serve as substrate for estrogen synthesis. The aim of this study was to investigate localization of the steroidogenic enzymes P450c17, 3βHSD, and P450arom and to determine changes in expression during dev...
Goff AK, Pontbriand D, Sirois J.In Exp. 1, 4 mares were given oxytocin intravenously (10 i.u./500 kg body wt) daily between Days 9 and 14 (Day 0 = day of ovulation) when pregnant and on Days 9-14, 16, 18, 20 when non-pregnant (not inseminated). In the non-pregnant mares the increase in plasma PGFM response to oxytocin was greater at Day 13 (235 +/- 54 pg/ml) than at Day 11 (113 +/- 38 pg/ml; P less than 0.05) and was maximum at Day 16. However, these animals did not return to oestrus and plasma progesterone did not fall below 4 ng/ml. There was no significant increase in response to oxytocin between Days 9 and 14 in the preg...
Fowden AL, Forhead AJ, Ousey JC.Delivery of viable young requires co-ordination of fetal maturation with the onset of labour at term. In turn, this depends on a cascade of fetal and maternal endocrine events. The sequence of these events is broadly similar in most mammals but there are differences in placental hormone synthesis and in the timing and magnitude of key prepartum endocrine changes between species. In most farm animals, maternal progesterone (P4) levels decline and oestrogen levels increase in the last 5 - 10 days before delivery in response to activation of the fetal hypothalamicpituitary-adrenal (HPA) axis and ...
Sipahutar H, Sourdaine P, Moslemi S, Plainfossé B, Séralini GE.High levels of plasma estrogens constitute an endocrine peculiarity of the adult stallion. This is mostly due to testicular cytochrome p450 aromatase, the only irreversible enzyme responsible for the bioconversion of androgens into estrogens. To identify more precisely the testicular aromatase synthesis sites in the stallion, testes from nine horses (2-5 years) were obtained during winter or spring. Paraplast-embedded sections were processed using rabbit anti-equine aromatase, followed by biotinylated goat anti-rabbit antibodies, and amplified with a streptavidin-peroxidase complex. Immunoreac...
Rambags BP, van Tol HT, van den Eng MM, Colenbrander B, Stout TA.Progesterone and oestrogen play essential roles in the maintenance of pregnancy in eutherian mammals and are thought to exert their effects on the developing conceptus indirectly, via the endometrium. In some species, early embryos have themselves been shown to express steroid receptors, thereby suggesting that reproductive steroids may also influence embryonic development directly. The aim of this study was to determine whether early intrauterine equine conceptuses express either the classical intracellular progesterone (PR) and oestrogen receptors (ERalpha and ERbeta) or the more recently ch...
Arkoun B, Gautier C, Delalande C, Barrier-Battut I, Guénon I, Goux D, Bouraïma-Lelong H.Among mammals, the stallion produces the largest amount of testicular estrogens. These steroid hormones are produced mainly by Leydig and Sertoli cells in the testis and also in the epididymis. Their role in horse testicular physiology and their ability to act on spermatozoa are still unknown. In order to determine if spermatozoa are targets for estrogens, the presence of estrogen receptors in mature ejaculated spermatozoa has been investigated. The presence of a single isoform of ESR1 (66kDa) and ESR2 (61kDa) was found by Western-blot analysis in samples from seven stallions. Confocal analysi...
Raeside JI, Christie HL, Renaud RL, Waelchli RO, Betteridge KJ.Because estradiol (E(2)) production by the early equine conceptus is considered crucial to the establishment of pregnancy, the amounts of E(2), estrone (E(1)), and their sulfates (E(2)S, E(1)S) were measured by RIA in yolk-sac fluid of 63 conceptuses collected by transcervical lavage over the period of 11-26 days after ovulation. Amounts increased significantly with age of conceptus, especially for E(1)S. Then, the metabolism of E(2), which may be highly relevant for its action, was examined in the conceptus and endometrium over the period when the conceptus ceases to migrate within the uterus...
Gerstenberg C, Allen WR, Stewart F.Previous studies showed a dramatic increase in EGF gene expression in the endometrial glands of pregnant mares around day 40 after ovulation. To investigate how the steroid hormones of pregnancy might regulate this expression, in situ hybridization was used to monitor the levels of EGF mRNA in endometrial biopsies obtained from seasonally anoestrous or ovariectomised mares given exogenous progesterone and oestrogen, alone or in combination, for up to 46 days. Biopsies were also taken from mares during the non-pregnant cycle, during normal pregnancies and pregnancies compromised by endometrial ...
Hejmej A, Gorazd M, Kosiniak-Kamysz K, Wiszniewska B, Sadowska J, Bilińska B.Androgen metabolism may proceed to amplify the action of testosterone by its aromatisation to oestradiol. Recently, a growing body of evidence suggests a role of oestrogens in the male reproductive tract via their specific oestrogen receptors (ERs). In order to check whether androgens are converted to oestrogens in the testis, epididymis and prostate of the stallion, the expression of aromatase was visualised by means of immunohistochemistry. Moreover, to show the cellular targets for oestrogens the presence of oestrogen receptor alpha (ERalpha) and oestrogen receptor beta (ERbeta) was demonst...
Kirkpatrick JF, Turner JW, Liu IK, Fayrer-Hosken R, Rutberg AT.Non-lethal management methods are required for wild equids that are protected by law and for deer inhabiting areas where lethal controls are not legal or safe. Single or multiple inoculations of porcine zona pellucida (PZP) vaccine have been delivered to wild horses and deer by means of darts. Contraceptive efficacy in horses after two inoculations ranged from 90% to 100%, and after a single inoculation ranged from 19% to 28%. Mares given a controlled-release form of the vaccine had foaling rates ranging from 7% to 20%. No detectable changes in social organization or behaviours among treated h...
Legacki EL, Corbin CJ, Ball BA, Scoggin KE, Stanley SD, Conley AJ.Steroidogenic enzymes in placentas shape steroid hormone profiles in the maternal circulation of each mammalian species. These include 3β-hydroxysteroid dehydrogenase/Δ5-4 isomerase (3βHSD) and 17α-hydroxylase/17,20-lyase cytochrome P450 (P450c17) crucial for progesterone and androgen synthesis, respectively, as well as aromatase cytochrome P450 (P450arom) that converts Δ4-androgens to estrogens. 5α-reductase is another important enzyme in equine placentas because 5α-dihydroprogesterone (DHP) sustains pregnancy in the absence of progesterone in the second half of equine pregnancy. DHP a...
Herrera-Luna CV, Scarlet D, Walter I, Aurich C.The aim of the present study was to characterise receptors for LH and FSH (LHR and FSHR, respectively) and aromatase in epididymal and testicular tissue from stallions of different ages (prepubertal, young, mature and old). Gene and protein expression were assessed by real-time quantitative polymerase chain reaction (real-time qPCR), immunohistochemistry and multiple immunofluorescence labelling. There were no differences in LHR mRNA expression in epididymal and testicular parenchyma in stallions of different age. In contrast, expression of FSHR and CYP19A1 in caput, corpus and cauda epididymi...
Esteller-Vico A, Ball BA, Troedsson MHT, Squires EL.Equine pregnancy is characterized by very high circulating concentrations of estrogens. The physiological roles of estrogens during equine gestation are largely unknown, although some studies suggest a role in the regulation of uterine artery hemodynamics and a relationship between low circulating estrogen concentrations and late pregnancy loss. The objectives of this experiment were to evaluate the effects of estrogen suppression on uterine artery hemodynamics and on pregnancy outcome. Estrogen synthesis was suppressed using letrozole, a potent aromatase inhibitor. Twelve pregnant mares were ...
McDowell KJ, Adams MH, Adam CY, Simpson KS.Two experiments were performed to determine changes in the abundance of oestrogen and progesterone receptor (ER alpha and PR) mRNAs in equine endometrium during the oestrous cycle and early pregnancy, and under the influence of exogenous steroids. In Expt 1, endometrial biopsies were obtained from non-mated mares during oestrus and at days 5, 10 and 15 after ovulation, and from pregnant mares at days 10, 15 and 20 after ovulation. There were overall effects of day on the abundance of ER alpha (P = 0.0001) and PR (P = 0.0014) mRNAs. The amount of ER alpha mRNA decreased at day 10 of pregnancy, ...
Chang M, Zhang F, Shen L, Pauss N, Alam I, van Breemen RB, Blond SY, Bolton JL.The risk factors for women developing breast and endometrium cancers are all associated with a lifetime of estrogen exposure. Estrogen replacement therapy (ERT) in particular has been correlated with a slight increased cancer risk, although the numerous benefits of ERT may negate this harmful side effect. Equilenin and equilin are equine estrogens which make up between 30% and 45% of the most widely prescribed estrogen replacement formulation, Premarin (Wyeth-Ayerst). In this study we have synthesized the catechol metabolites of equilenin [4-hydroxyequilenin (4-OHEN)] and equilin [4-hydroxyequ...
Schwarzenberger F, Möstl E, Bamberg E, Pammer J, Schmehlik O.Faecal samples were collected at weekly intervals from pregnant Lipizzan mares during Weeks 7-16 following mating and from Lipizzan, Trotter and Thoroughbred mares during the last 3 months of gestation. After parturition, samples were taken daily from the Thoroughbred mares for another 6 days. Non-pregnant mares served as controls. The concentrations of unconjugated oestrogens (Eg), 20 alpha-OH-progestagens (20 alpha-G) and 20 beta-OH-progestagens (20 beta-G) were measured by enzyme immunoassay. In the faeces of Lipizzan mares, immunoreactive progestagens were significantly (P less than 0.01) ...
Conley AJ, Ball BA.Historically, studies on the endocrinology of pregnancy and parturition in horses have made major contributions of relevance to mammals in general. Recent use of liquid chromatography mass spectrometry, measuring multiple steroid hormones simultaneously in blood, foetal and placental tissues throughout normal gestation, and in mares with experimentally induced placentitis, has advanced our current understanding of many of the unusual strategies seen during gestation and at foaling. This includes the stimulation of luteal steroidogeneisis by equine chorionic gonadotropin (eCG) from the endometr...
Ferreira-Dias G, Botelho M, Zagrajczuk A, Rebordão MR, Galvão AM, Bravo PP, Piotrowska-Tomala K, Szóstek AZ, Wiczkowski W, Piskula M, Fradinho MJ....Phytoestrogens exist in plants that are present in forages fed to horses. They may compete with 17-β estradiol and influence the estrous cycle. Therefore, the objective was to determine whether coumestrol from clover-mixed pastures is present in mare's plasma after their ingestion (experiment I), and when this phytoestrogen was present in mare's plasma after ingestion (experiment II). The effect of a long-term ingestion of phytoestrogens on estrous cycle disruption was assessed (experiment III; clinical case). Experiment I was carried out in nonpregnant anestrous and cyclic Lusitano mares (n ...
