The principle objective of the research program was to develop hormone free methods of controlling reproduction in small ruminants through natural manipulation of three environmental factors know to affect reproduction in small ruminants these are nutrition, photoperiod and socio-sexual signals.

Three research projects have been completed. The first project was a study of the effect of nutrition on seasonality of reproduction in sheep. The results show that undernutrition modified the photoperiod-driven expression of reproductive seasonality and that in the spring, reproductive activity stopped sooner in under nourished ewes that was associated with a reduction in circulating melatonin. Although the early results suggested that undernutrition altered the circadian clock that entrained the rhythm of melatonin this was confirmed by later studies. It now appears that undernutrition has effects on the amplitude of melatonin secretion that alters the secretion of GnRH. The results of parallel studies have shown that the energy sensing AMPK (adenosine mono phosphate kinase) system is implicated in this mechanism. Complimentary studies examining the site of the interaction between photoperiodic influences on reproduction suggest that the interaction occurs at the level of the GnRH pulse generating system.
A second project examined the interaction between nutrition and socio-sexual signals that affect reproduction. The main socio-sexual signal affecting reproduction in small ruminants is the "male effect", where by the introduction of a male into a group of females that are anoestrus (that is females that are not reproductively active) can stimulate reproductive activity in a high proportion of stimulated females. The first experiments described the effects of nutrition and genotype on the response to the male effect. From these studies a number of important scientific issues became apparent and so we addressed these. First, our studies revealed that the ovary was an important source of variability and highlights a critical need to examine the physiology of folliculogenesis in anoestrus and studies in this subject are now commencing at INRA. Secondly, studies with goats have shown an interaction between nutrition and the "male effect" but, using sheep in France we were unable to confirm this. Complimentary basic investigations into the follicular physiology of anoestrous ewes and its relationship to the ram effect have shown that short cycles are not caused by the premature secretion of uterine prostaglandin F2# and that they are associated with a suppression of progesterone synthesis associated with reduced gene expression of some essential components of the biosynthetic pathway for progesterone (e.g. StAR and 3#HSD). The project examined the effect of nutrition on folliculogenesis. In sheep, short-term nutritional supplementation stimulates folliculogenesis and understanding how is critical to the development the feeding systems required to develop hormone free manipulation of reproduction. These experiments have been carried out using sheep. In France, research examined the intra-ovarian insulin-glucose system while complimentary experiments in Tunisia examined how nutrition stimulated this insulin-glucose system. The results show that nutrition reduced the intra follicular concentration of aromatase in the granulosa without any change in the level of FSH and it was associated with a reduction in the secretion of follicular oestradiol but an increase in the number of follicles. Furthermore, these findings could be replicated by the infusion of glucose. These results demonstrate that the effect of nutritional supplementation on folliculogenesis is at the level of the follicle. Further analysis of samples from both these experiments have shown that both nutritional supplementation and infusion of glucose induced changes in follicular physiology that were associated with changes in the intra-follicular insulin signalling.

2007
1. Kershaw, C.M., Scaramuzzi, R.J., McGowan, M.R., Wheeler-Jones, C.P.D. and Khalid, M. (2007) The expression of prostaglandin endoperoxide 2 mRNA and the proportion of smooth muscle and collagen in the sheep cervix during the estrous cycle. Biology of Reproduction, 76, 124 - 129.

2. Laven, R.A., Scaramuzzi, R.J., Wathes, D.C., Peters, A.R. and Parkinson, T.J. (2007) Recent research on the effects of excess dietary nitrogen on the fertility in the dairy cow. The Veterinary Record, 160, 359 - 362.

3. Laven, R.A., Wathes, D.C. Lawrence, K.E. and Scaramuzzi, R.J. (2007) An analysis of the relationship between plasma urea and ammonia concentration in dairy cattle fed a consistent diet over a 100-day period. Journal of Dairy Research,74, 412 – 416.

4. Leethongdee, S., Khalid, M., Bhatti, A., Ponglowhapan, S., Kershaw, C.M. and Scaramuzzi, R.J. (2007) The effects of the prostaglandin E analogue Misoprostol and follicle stimulating hormone on cervical penetrability in ewes during the peri-ovulatory period. Theriogenology, 67, 767-777.

5. Llewellyn, S., Fitzpatrick, R., Kenny, D.A., Scaramuzzi, R.J. and Wathes, D.C. (2007) Effect of negative energy balance on the insulin-like growth factor system in pre-recruitment ovarian follicles of post partum dairy cows. Reproduction, 133, 627 -639.

6. Nargund, G., Hutchison, L., Scaramuzzi, R. and Campbell, S. (2007) Low-dose hCG is useful in preventing OHSS in high risk women without adversely affecting the outcome of IVF cycles. Reproductive Biomedicine Online, 14, 682 -685.

7. Ponglowhapan, S., Church, D.B., Scaramuzzi, R.J. and Khalid, M. (2007) Luteinizing hormone and follicle-stimulating hormone receptors are expressed at mRNA and protein levels in the normal canine lower urinary tract.  Theriogenology, 67, 353 – 366.

8. Somchit, A., Khalid, M., Campbell, B.K. and Scaramuzzi, R.J. (2007) The effects of short-term nutritional supplementation with lupins (Lupinus luteus) on the number of ovarian follicles and the concentrations of follicular hormones and glucose in ewes during the luteal phase of the oestrous cycle. Theriogenology 68, 1037 - 1046.

9. Spattini. G., Borghi, V., Thuróczy, J., Balogh, L., Scaramuzzi, R.J. and F. De Rensis, F. (2007) Follicular development and plasma concentrations of LH and prolactin in anestrous female dogs treated with the dopamine agonist, Carbergoline. Theriogenology, 68, 826 – 833.

2008
1. Catchpole, B., Mountford, M., Barabas, S. and Rex J. Scaramuzzi, R.J. (2008) Evaluation of a disposable device for the measurement of haemoglobin A1c in dogs The Veterinary Record, 162, 47 – 49

2. De Santiago-Miramontes, M.A., Rivas-Muñoz, R., Muñoz-Gutiérrez, M., Malpaux, B., Scaramuzzi, R.J. and Delgadillo, J.A. (2008) Ovulation rate in female anoestrous goats exposed to the male effect is increased by nutritional supplementation under grazing conditions. Animal Reproduction Science, 105, 409 -416.

3. De Rensis, F., Lopez-Gatius, F., Capelli, T., Molina E., Techakumphu, M. and Scaramuzzi, R.J. (2008) Effect of season on luteal activity during the post partum period of dairy cows in temperate areas. Animal, 2, 554 -559.

4. Scaramuzzi, R.J. and Martin, G.B. (2008) The importance of interactions among nutrition, seasonality and socio-sexual factors in the development of hormone free methods for controlling fertility Reproduction in Domestic Animals, 43 Supplement 2, 129 - 136.

2009
1. Chanvallon, A., Sagot, L., Pottier, E., Scaramuzzi, R.J. and C Fabre-Nys, C. (2009) Interaction among seasonality of reproduction, genotype and the ram effect. Archiva Zootechnicia, 12, 73 – 81.

2. Chanvallon, A. Sagot, L. Scaramuzzi, R., Francois, D., Fassier, T. and Fabre-Nys, C. (2009) Intérêts de l’effet bélier en contre saison selon le type génétique. Rencontres, Recherches Ruminants, 16, 309 – 213.

3. Fitz-Rodríguez, G., De Santiago-Miramontes, M.A., Scaramuzzi, R.J., Malpaux, B. and Delgadillo, J.A. (2009). Nutritional supplementation improves ovulation and pregnancy rates in female goats managed under natural grazing conditions and exposed to the male effect. Animal Reproduction Science, 116, 85 – 94.

4. Kershaw, C.M, Khalid, M., McGowan, M.R., Pitsillides, A.A., and Scaramuzzi, R.J. (2009). The mRNA expression of EP2 and EP4 and the changes in glycosoaminoglycans in the sheep cervix during the oestrous. Theriogenology, 72, 251 – 261.

2010
1. Campbell, B.K., Onions, V., Kendall, N.R., Guo, L. and Scaramuzzi, R.J. (2010) The effect of monosaccharide sugars and pyruvate on the differentiation and metabolism of sheep granulosa cells in vitro. Reproduction, 140, 541-550.

2. Campbell, B.K., Kendall, N.R., Onions, V., and Scaramuzzi, R.J. (2010) The effect of systemic and ovarian infusion of glucose, galactose and fructose on ovarian function in sheep. Reproduction, 140, 721-732.

3. Chanvallon, A., Scaramuzzi R.J. and Fabre-Nys, C. (2010) Early sexual experience and stressful conditions affect the response of young ewes to the male. Physiology and Behaviour, 99, 457 – 465.

4. Chemineau, P., Menassol, J-B., Scaramuzzi, R.J. and Malpaux, B. (2010) Seasonal rhythms of reproductive activity in sheep and goats are driven by photoperiod but modulated by the male effect and nutrition. In: Simposio internacional fisiología Reproductive en Mamíferos, Eds : Minerva Muñoz Gutiérrez, José Alberto Delgadillo Sánchez, María Del Socorro I. Retana Márquez pp 31-51. Universidade Autonóma Matropolitana, Mexico City, Mexico.

5. Chowdhury, W.M.H., Scaramuzzi, R.J., Wheeler-Jones, C.P.D. and Khalid, M. (2010) The mRNA expression of angiogenic growth factors and their receptors in ovarian follicles changes with the stage of the oestrous cycle in the ewe. Theriogenology, 73, 856 – 872.

6. Kershaw-Young, C.M., Scaramuzzi, R.J., McGowan, M.R., Pitsillides, A.A., Caroline P.D. Wheeler-Jones, C.P.D. and Khalid, M. (2010) The effect of oestradiol on COX-2, EP2 and EP4 mRNA expression and the extracellular matrix in the cervix of the hypogonadotrophic ovariectomised ewe Theriogenology, 73, 620 – 628.

7. Leethongdee, S., Scaramuzzi, R.J., Kershaw-Young, C.M. and Khalid, M (2010) The effects of the prostaglandin E analogue Misoprostol and follicle stimulating hormone on FSH-R and LH-R mRNA in ewes during the oestrous cycle. Theriogenology, 73, 1257 – 1266.

8. Scaramuzzi, R.J., Brown, H.M. and Dupont, J. (2010) Nutritional and metabolic mechanisms in the ovary and their role in mediating the effects of diet on folliculogenesis: A perspective. Reproduction in Domestic Animals 45, (Suppl 3) 32 – 41.

9. Scaramuzzi, R.J., Campbell, B.K., Souza, C.J.H. and Baird, D.T. (2010) Glucose uptake and lactate production by the autotransplanted ovary of the ewe during the luteal and follicular phases of the oestrous cycle. Theriogenology 73, 1061 – 1067.

10. Sébert, M.-E., Lomet, D., Ben Saïd, S., Monget, P., Briant, C., Scaramuzzi R.J. and Caraty, A. (2010) Insights into the mechanism by which kisspeptin stimulates a preovulatory LH surge and ovulation in seasonally acyclic ewes: potential role of estradiol. Domestic Animal Endocrinology 38, 289 – 298.

2011
1. Scaramuzzi, R.J., Baird, D.T., Campbell, B.K., Driancourt, M-A., Dupont, J., Fortune, J.E., Gilchrist, R.B., Martin, G.B., McNatty, K.P., McNeilly, A.S., Monget, P., Monniaux, D., Viñoles Gil, C. and Webb, R. (2010) Regulation of folliculogenesis and the determination of ovulation rate in ruminants: A review. Reproduction, Fertility and Development, (In Press; Accepted for publication)

1. Chanvallon, A., Sagot, L., Pottier, E., Debus, N., François, D., Fassier, T., Scaramuzzi, R.J. and Fabre-Nys, C. (2011) New insights into the influence of breed and time of the year on the response of ewes to the “ram effect. Animal, (Submitted)

2. Chowdhury, W.M.H., Scaramuzzi, R.J., Wheeler-Jones, C.P.D. and Khalid, M. (2011) The effect of the pre ovulatory luteinizing hormone surge on the mRNA and protein expression of angiogenic growth factors in the ovine ovary. (In Draft)

3. Chowdhury, W.M.H., Scaramuzzi, R.J., Wheeler-Jones, C.P.D. and Khalid, M. (2011) The effect of the pre ovulatory luteinizing hormone surge on the mRNA and protein expression of Angiopoietin-Tie system in the ovine ovary. (In Draft)

4. Gallet, C., Dupont, J., Campbell, B.K., Monniaux, D. and Scaramuzzi, R.J. (2011) The infusion of glucose in ewes during the luteal phase increases the number of follicles but reduces oestradiol production and some metabolic parameters in follicles. Animal Reproduction Science, (In Press, subject to revision)

5. Johnson, L. Fabre-Nys, C., Chanvallon, A., François, D., Fassier, T. Menassol, J-B., Brown, H.M., Lardic, L. and Scaramuzzi, R.J. (2011) The effect of short-term nutritional supplementation and body condition score on the ovarian responses of anoestrus ewes to the “ram effect”. Reproduction, Fertility and Development, (In Press, subject to revision)

6. Leethongdee, S., Khalid, M. and Scaramuzzi, R.J. (2011) The effect of the administration of intra-cervical Follicle stimulating hormone (FSH) or Luteinizing hormone (LH) on the pattern of expression of gonadotrophin receptors in the cervix of non-pregnant Welsh Mountain ewes. Theriogenology, (In Draft)

7. Somchit-Assavacheep, A., Khalid, M., Campbell, B.K. and Scaramuzzi, R.J. (2011) Effects of short-term nutritional supplementation of ewes with lupins (Lupinus luteus), on folliculogenesis, the concentrations of hormones and glucose in plasma and follicular fluid and the follicular expression of P450 aromatase, IRS-1, 2 and 4.  (In Draft)

8. Menassol, J-B., Tautou, C., Collet, A., Chesneau, D., Lomet, D., Dupont, J., Malpaux, B. and Scaramuzzi, R.J. (2011) Effect of a metformin and AICAR intracerebroventricular injection on plasma melatonin levels in ewe: potential involvement of AMPK. Neuroendocrinology (Submitted)

9. Falchi, L. Taema, M. Le Clanche, S. and Scaramuzzi R.J. (2011) Patterns of cervical penetration during the peri-ovulatory period and the effect of topical treatment with hormones on the relaxation of the cervix in the sheep(In Draft)
10.    Falchi, L (2011) Penetration paper

11. Menassol, J-B., Tautou, C., Collet, A., Chesneau, D., Lomet, D., Dupont, J., Malpaux, B. and Scaramuzzi, R.J. (2011) The effect of long-term nutrition on the seasonal rhythms of reproduction and plasma LH concentration a seasonal and a non-seasonal breed of sheep (In Draft)
 

2007
1. Chowdhury, M.W.H., Scaramuzzi, R.J., Wheeler-Jones, C.P.D. and M Khalid, M. (2007) Angiogenic growth factors in ovine follicles and corpora lutea. Proceeding of ESDAR, Annual Meeting Germany September 2007.

2. Kershaw-Young, C.M., Khalid, M. McGowan, M.R. and Scaramuzzi, R.J. (2007) Cervical COX-2, EP2 and EP4 mRNA in the ovariectomised ewe. Proceedings of the Society for the Study of Reproduction, Annual Meeting York, July 2007.

3. Leethongdee, S., Kershaw, C.M, Scaramuzzi, R.J. and Khalid, M. (2007) Misoprostol increases the expression of the Hyaluronan content in the sheep cervix. Proceedings of the Society for the Study of Reproduction, Annual Meeting York, July 2007.

4. Leethongdee, S. Khalid, M. and Scaramuzzi, R.J. (2007) The effect of intra-cervical LH and FSH on FSH-R mRNA expression in the cervix of the oestrous ewe. Proceeding of ESDAR, Annual Meeting Germany September 2007.

5. Somchit, A., Campbell, B.K., Khalid, M. and Scaramuzzi, R.J. (2007) The effect of lupins on plasma and follicular fluid hormones and P450 aromatase in ovine granulosa cells. Proceedings of the Society for the Study of Reproduction, Annual Meeting York, July 2007.

6. Somchit, A., Campbell, B.K., Khalid, M. and Scaramuzzi, R.J. (2007) The expression of insulin receptor substrate (IRS) protein-1 in theca and granulosa cell in sheep fed with lupin grain, Meeting of the 9th  National Ovarian Workshop, Cambridge, September 2007.


2008
1. Leethongdee, S., Khalid, M. and RJ Scaramuzzi, R.J. (2008) Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) induce the expression of cyclooxygenase -2 mRNA in cervical tissue of non-pregnant ewes. Proceedings of the International Congress on Animal Reproduction, Budapest July 2008

2. Fitz-Rodríguez, G., De Santiago-Miramontes, M.A., Scaramuzzi, R.J., Malpaux, B. and Delgadillo, J.A. (2008) Nutritional supplementation improves ovulation rate in goats subjected to the ‘male effect’ under natural grazing conditions. Proceedings of the International Goat Association (Queretaro, Mexico, from August - September 2008).

3. Muñoz-Gutiérrez, M. Scaramuzzi, R.J., Escobedo Alcántara, J.C., Trejo-González, A., Retana-Márquez, M.S., Damian Matzumura, P. and Borregos de Patria Nueva, A.C. (2008) Short term nutritional supplementation improves reproductive performance in ewes maintained under extensive conditions in arid central Mexico. Proceedings of the International Congress on Animal Reproduction, Budapest July 2008

4. Muñoz-Gutiérrez, M., Scaramuzzi, R.J., Escobedo Alcántara, J.C., Trejo-González, C.A., Murcia-Mejía, C., Retana-Márquez, M.S., Damian-Matzumura, P., Bonilla-Jaime, H., Arteaga-Silva, M. and Borregos de Patria Nueva, A.C. (2008) Seven days of nutritional supplementation improve both reproductive performance and ovulation rate in ewes maintained under extensive conditions in arid central Mexico XXI Congreso Panamericano de Ciencias Veterinarias (PANVET)  October 2008 Guadalajara Jalisco, México.


2009
1. De Ambrogi, M., Falchi, L., Onions, V., Campbell, B.K. and Scaramuzzi, R.J. (2009) Effect of infusion of glucose and hemi-ovariectomy on ovarian follicles and hormonal levels in sheep. Proceedings of ESDAR, Utrecht, September 2009

2. Kendall, N.R., Onions, V.J., Scaramuzzi R.J. and Campbell, B.K. (2009) The effect of systemic and ovarian infusion of glucose, galactose and fructose on ovarian function in sheep. Proceedings of the Society for the Study of Reproduction (Edinburgh Jan 2009)

3. Falchi, L., Taema, M., Khalid, M. and Scaramuzzi, R.J. (2009) The effect of the local administration of FSH and/or Misoprostol on cervical penetration in the ewe during the peri-ovulatory period. Proceedings of ESDA, Utrecht, September 2009

4. Falchi, L. Perry, K., Khalid, M. and Scaramuzzi, R.J. (2009) The expression of oxytocin receptor, c-phospolipase A2 and cyclooxygenase 2 in the
cervix of ewes during the oestrous cycle.  Proceedings of ESDAR, Utrecht, September 2009

5. Falchi, L. and Scaramuzzi, R.J. (2009) Effect of FSH and 17ß-oestradiol on in vitro levels of PGE2 and COX-2 in explants of cervical tissue from ewes in the follicular phase Proceedings of the Society for the Study of Reproduction (July 2009).

2010
1. Leethongdee, S., Khalid, M. and Scaramuzzi, R.J.  (2010) Luteinizing Hormone and follicle stimulating hormone induce COX -2 in the ovine cervix. Proceedings of the annual meeting of ESDAR, Eger, Hungary, September 2010.

2. Leethongdee, S., Khalid, M. and Scaramuzzi, R.J.  (2010) The effect of intra-cervical LH and FSH on LHR mRNA in cervical tissue from oestrous ewes. E Proceedings of the annual meeting of ESDAR, Eger, Hungary, September 2010.

3. Ramos-Rojas, A.L., Gijón-Palafox, L., Trejo-González, A.A., Delgadillo, J.A., Soriano-Robles, R., Murcia-Mejía, C., Retana-Márquez, M.S., Scaramuzzi, R.J., Martin, G.B. and Muñoz-Gutiérrez, M. (2010) The male effect improves reproductive performance in ewes maintained under extensive conditions in arid central Mexico. Proceedings of the 8th International Symposium on Reproduction in Domestic Ruminants, Anchorage, Alaska, USA September 2010.

4. Menassol, J-B., Chesneau, D., Collet, A., Malpaux, B; and Scaramuzzi, R.J. (2010). Photoperiod and nutrition interact centrally to modulate the seasonal pattern of reproduction in sheep. Proceedings of the Society for the Study of Reproduction (University of Nottingham, July 2010).

5. Brown, H.M., Fabre-Nys, C. and Scaramuzzi, R.J. (2010). Dysregulation of pathways controlling hormone production and vascular development and function in the corpora lutea of short cycles following the ram effect. Proceedings of the Society for the Study of Reproduction (University of Nottingham, July 2010).