The Paul Mellon Laboratory of Equine Reproduction

Newmarket, United Kingdom

The Paul Mellon Laboratory of Equine Reproduction

Newmarket, United Kingdom

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Lehmann J.,University of Leipzig | Ellenberger C.,University of Leipzig | Hoffmann C.,University of Leipzig | Bazer F.W.,Texas A&M University | And 4 more authors.
Theriogenology | Year: 2011

The aim of the present study was to characterize the morpho-functional features of endometrosis in barren and foaling mares, using both conventional histopathological and immunohistochemical methods. Endometrial biopsy samples were collected during the physiological breeding season from 159 estrous, clinically healthy mares (mean age 12 years), and the quality and degree of endometrosis was histomorphologically defined. The mares were bred and those that foaled were put in the foaling group whereas those that did not foal were placed in the barren group. Foaling mares were then compared with barren mares. Sixty-four percent (101/159) of uterine samples showed varying degrees of endometrosis and were used for this study. The sample population consisted of 51 barren and 50 foaling mares suffering from endometrosis. Expression of steroid hormone receptors (estrogen receptor, progesterone receptor) and endometrial protein secretion patterns (uteroglobin [UG], uterocalin [UC], calbindin D9k [CAL], uteroferrin [UF]) was evaluated by immunohistochemistry (barren mares N = 51, foaling mares N = 31). In comparison with unaffected glands, fibrotic glands generally showed a cycle-asynchronous, partially patchy protein expression pattern which is interpreted as a sign of endometrial maldifferentiation within fibrotic areas. In barren mares (N = 51) more than half of biopsy samples (27/51) showed a destructive mostly moderate (20/27) type of endometrosis. In affected glands, staining for UG (17/21) was decreased (P < 0.001). Foaling mares (N = 50) frequently showed a mild, nondestructive endometrosis (35/50). Compared with barren mares, foaling mares had statistically (P < 0.05) more often a cycle-synchronous or increased UG expression pattern within fibrotic glands. Obvious deviations of either UG or UC rarely occurred. Within fibrotic foci, UF often demonstrated a cycle-synchronous or more intense expression pattern in both foaling (28/31) and barren mares (41/51), compared with healthy glands. Mares of both groups showed a cycle-asynchronous staining for estrogen receptor and progesterone receptor in the stromal cells in areas of periglandular fibrosis and the glandular epithelia. These findings indicate that affected areas become independent of the uterine control mechanisms and exhibit specific differentiation dynamics. Immunohistochemical investigations showed that the secretory patterns differ between barren and foaling mares. The findings in this study should be considered as a useful addition to the "classical" Kenney categorization. © 2011 Elsevier Inc.


Veronesi M.C.,University of Milan | Villani M.,University of Milan | Villani M.,University Utrecht | Wilsher S.,The Paul Mellon Laboratory of Equine Reproduction | And 2 more authors.
Theriogenology | Year: 2010

The aim of the study was to compare horse and donkey placentae using stereological techniques. Term placentae were collected at spontaneous foaling from seven Thoroughbred mares, seven pony mares, and six jenny donkeys. Maternal and foal weights were recorded and the mass, volume, and gross area of each allantochorion was also recorded. Ten random biopsies were recovered and processed for light microscopy from which the surface density of the microcotyledons (Sv) and the total microscopic area of fetomaternal contact were calculated stereologically. Gestation length was longer in the donkeys than the other two groups (median values: 371 vs. 327 and 341 days, P < 0.05). There were significant correlations between foal birthweight and gross area (rho = 0.89; n = 20; P < 0.05), mass (rho = 0.84; n = 20; P < 0.05) and volume (rho = 0.89; n = 20; P < 0.05) of the allantochorion. Sv was higher in the donkey placenta than the other groups (median values: 0.05 vs. 0.03 and 0.04 μm-1, P < 0.05) although placental efficiency was lower in the donkeys (median values: 0.87 vs. 1.33 and 1.32 kg/m2, P < 0.01). The results of the study confirmed that, although strong morphological similarities exist between the allantochorion of the horse and donkey, that of the donkey develops more complex microcotyledons, as judged stereologically, and exhibits a lower placental efficiency. These differences may be related to maternal genotype and/or the longer gestation length shown by the donkey compared to the horse, but a negative correlation (rho = -0.92, P < 0.01) was also found between age and placental efficiency in donkeys. © 2010.


Wilsher S.,The Paul Mellon Laboratory of Equine Reproduction | Wilsher S.,The Equine Fertility Unit | Allen W.R.,The Paul Mellon Laboratory of Equine Reproduction
Equine Veterinary Journal | Year: 2011

Reasons for performing study: An opportunity to monitor equine chorionic gonadotrophin (eCG) production during 61 pregnancies in 25 Thoroughbred mares mated to the same Thoroughbred stallion was utilised in order to further knowledge regarding factors involved in the production of this hormone. Objectives: To examine the effects of maternal body condition, exercise and parity on eCG production. Methods: In the first experiment, maiden mares were fed either a moderate (n = 9) or an excessive (n = 10) food intake throughout gestation. In the second experiment, 5 mares were exercised daily during pregnancy and eCG production rates were compared to 5 nonexercised mares. In the third experiment, eCG profiles were compared in 9 mares during 3 successive pregnancies. Equine chorionic gonadotrophin secretion was assessed as area under the curve (AUC), peak serum concentration, timing of the peak and the rate of decline. In addition, a mean eCG profile of 61 pregnancies was created to provide means and ranges for the above parameters. Results: In Experiment 1, eCG production was significantly higher in moderately rather than excessively fed mares in terms of AUC and peak eCG concentrations. In Experiment 2, the mean AUC did not differ between exercised and nonexercised animals but mean eCG concentrations were significantly higher in nonexercised mares between Days 60 and 90 of gestation. In Experiment 3, eCG became undetectable significantly earlier in gestation in the third parity. The mean eCG profile of 61 pregnancies showed a peak of 64.5 ± 3.7iu/ml at 62.4 ± 1.0 days after ovulation and was undetectable by 134.1 ± 1.7 days. Peak eCG levels reduced by 50% 22.6 ± 1.13 days. Conclusions: Some of the factors examined clearly influenced eCG production rate, the secretion of this hormone and its rate of disappearance from the blood. Potential relevance: The results provide insights into some factors that govern the production of the placental gonadotrophin, eCG. © 2011 EVJ Ltd.


Wilsher S.,The Paul Mellon Laboratory of Equine Reproduction | Allen W.R.,The Paul Mellon Laboratory of Equine Reproduction
Equine Veterinary Journal | Year: 2012

The development of the equine placenta involves a series of stage-specific events which ensure that the fetus is nourished throughout its 11 months of gestation. Initially, placental exchange to the developing embryo is histotrophic, via the yolk sac but, as the allantochorion develops and microcotyledons form, haemotrophic nutrition plays the major role in sustaining the increasing demands of the growing fetus. This review describes the development of the allantochorionic placenta of the mare and discusses some of the factors that influence its growth, size and functions and, hence, its control of fetal growth and maturation. © 2012 EVJ Ltd.


Hautier L.,University of Cambridge | Stansfield F.J.,The Elephant Research Unit | Twink Allen W.R.,The Paul Mellon Laboratory of Equine Reproduction | Asher R.J.,University of Cambridge
Proceedings of the Royal Society B: Biological Sciences | Year: 2012

We provide here unique data on elephant skeletal ontogeny. We focus on the sequence of cranial and post-cranial ossification events during growth in the African elephant (Loxodonta africana). Previous analyses on ossification sequences in mammals have focused on monotremes, marsupials, boreoeutherian and xenarthran placentals. Here, we add data on ossification sequences in an afrotherian. We use two different methods to quantify sequence heterochrony: the sequence method and event-paring/Parsimov. Compared with other placentals, elephants show late ossifications of the basicranium, manual and pedal phalanges, and early ossifications of the ischium and metacarpals. Moreover, ossification in elephants starts very early and progresses rapidly. Specifically, the elephant exhibits the same percentage of bones showing an ossification centre at the end of the first third of its gestation period as the mouse and hamster have close to birth. Elephants show a number of features of their ossification patterns that differ from those of other placental mammals. The pattern of the initiation of the ossification evident in the African elephant underscores a possible correlation between the timing of ossification onset and gestation time throughout mammals. @ 2012 The Royal Society.


Wilsher S.,The Paul Mellon Laboratory of Equine Reproduction
Equine veterinary journal. Supplement | Year: 2012

The development of the equine placenta involves a series of stage-specific events which ensure that the fetus is nourished throughout its 11 months of gestation. Initially, placental exchange to the developing embryo is histotrophic, via the yolk sac but, as the allantochorion develops and microcotyledons form, haemotrophic nutrition plays the major role in sustaining the increasing demands of the growing fetus. This review describes the development of the allantochorionic placenta of the mare and discusses some of the factors that influence its growth, size and functions and, hence, its control of fetal growth and maturation.


Allen W.R.T.,The Paul Mellon Laboratory of Equine Reproduction
Animal Reproduction Science | Year: 2010

Genus-specific reproductive processes and strategies displayed by equids, camelids and elephantids are compared and contrasted to illustrate the amazing diversity of reproductive physiology between genera and the equally surprising conservation of reproductive processes across a genus in the face of other dramatic phenotypic modifications and adaptation to prosper in the prevailing environment. From intrauterine conceptus mobility and chorionic gonadotrophic secretion by specialised invasive trophoblast cells in equids, through induced ovulation, an asymmetrical uterus and an almost absurdly short dioestrous interval in camelids, to intrabdominal testes, the testosterone-driven expression of musth and a very tenuous intrauterine attachment of the placenta in elephantids, reproductive physiology remains a discipline of great fascination and academic merit with much yet to be discovered and understood across the whole mammalian kingdom. © 2010 Elsevier B.V.


Wilsher S.,The Paul Mellon Laboratory of Equine Reproduction | Gower S.,The Paul Mellon Laboratory of Equine Reproduction | Allen W.R.T.,The Paul Mellon Laboratory of Equine Reproduction
Animal Reproduction Science | Year: 2011

Previous reports documenting progesterone receptors (PR) and oestrogen receptors (ER) in the endometrium of early pregnant mares included specimens only up to Day 20 post ovulation. This study aimed to localise PR and ERα on equine feto-maternal tissues between Days 20 and 68 to encompass the period around fixation of the conceptus, development of the endometrial cups and attachment and initial interdigitation of the allantochorion. During early pregnancy mares had the same pattern of PR in the endometrium as that reported for other mammals; namely, a loss of PR from the endometrial epithelia but continued localisation in stromal cells. The spatial arrangement of ERα over the same time period showed cytoplasmic staining of endometrial epithelia and in the nuclei of occasional stromal cells. In the fetal tissues, no cells had PR although ERα was evident in some tissue compartments. No major change in localisation of either receptor was noted throughout the time period examined despite important changes occurring at the placental interface. Nevertheless, these steroid receptor molecules probably play important roles in the production of histotroph and growth factors by the endometrium which go on to stimulate differentiation and growth of the feto-maternal tissues. © 2011 Elsevier B.V.


PubMed | The Paul Mellon Laboratory of Equine Reproduction
Type: Journal Article | Journal: Equine veterinary journal | Year: 2012

During embryo transfer (ET) the equine embryo can tolerate a wide degree of negative asynchrony but positive asynchrony of >2 days usually results in embryonic death. There is still confusion over whether this is due to the inability of the embryo to induce luteostasis or to an inappropriate uterine environment.To assess embryo survival and development in an advanced uterine environment.Embryo-uterine asynchrony, not the embryos inability to induce luteostasis, is responsible for embryonic death in recipient mares with a >2 days chronologically advanced uterus.Experiment 1: Thirteen Day 7 embryos were transferred to the uteri of recipient mares with luteal prolongation, occasioned by manual crushing of their own conceptus, such that donor-recipient asynchrony was between +13 and +49 days. Experiment 2: Day 7 embryos were transferred to recipient mares carrying their own conceptus at Days 18 (n = 2), 15 (n = 2), 14 (n = 4), 12 (n = 4) or 11 (n = 4) of gestation. In addition, Day 8 embryos were transferred to 4 pregnant recipient mares on Day 11 of gestation.No pregnancies resulted following transfer of Day 7 embryos to recipients in prolonged dioestrus with asynchronies between +13 and +49 days. However, the use of early pregnant mares as recipients resulted in 5/20 (25%) twin pregnancies, 4 of which came from the transfer of a Day 8 embryo to a Day 11 recipient. All transferred embryos showed retarded growth, with death occurring in 4/5 (80%).The results emphasise the importance of an appropriate uterine environment for embryo growth and the inability of equine embryos to survive transfer to a uterus >2 days advanced even when luteostasis is achieved. It is possible that in normal, non-ET equine pregnancy, embryo-uterine asynchrony may account for some cases of embryonic death.


PubMed | The Paul Mellon Laboratory of Equine Reproduction
Type: Journal Article | Journal: Reproduction, fertility, and development | Year: 2013

A polyclonal human mucin-1 (MUC1) antibody was used to stain immunohistochemically for the presence of MUC1 on the endometrium and fetal membranes in mares between 20 and 309 days of gestation. Western blot analysis demonstrated the presence of a protein equivalent in size to a human MUC1 isoform, MUC1/Y, in equine endometrium, allantochorion and amnion. At all stages of gestation examined immunoreactivity to the MUC1 antibody was detected on the apical surface of the lumenal epithelium of the endometrium and the epithelium lining the mouths and apical regions of the endometrial glands. Furthermore, it persisted unchanged on the surface of the lumenal epithelium lying beneath the highly-invasive chorionic girdle component of the trophoblast before, during and after development of the endometrial cups. The MUC1 immunoreactive protein was also present on the trophoblast and other components of the fetal membranes during the post-fixation, pre-attachment period of gestation (20-40 days) and it persisted on the apical surface of the non-invasive trophoblast of the allantochorion before, during and after attachment, microvillous interdigitation and development of the microcotyledonary epitheliochorial placenta. Hence, the delayed placentation response in mares appears to occur independently of the persistence of an immunoreactive MUC1 protein at the feto-maternal interface.

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