Reproduction in Domestic Animals

108 RS Robinson, AJ Hammond, DC Wathes, MG Hunter and GE Mannand its up-regulation coincided with that of blastocystelongation. It is feasible that IGFBP1 increases IGFavailability for the embryo by regulating the transportof endometrial IGF1 to the uterine lumen. Moreover,the embryo may enhance this process by stimulatingIGFBP1 expression even more. In human implantation,there is considerable evidence for a specific role ofIGFBP1 in enhancing trophoblast invasiveness (Hamiltonet al. 1998). Also IGFBP1 mRNA and endometrialPGR were inversely correlated suggesting that progesteronesuppresses IGFBP1 mRNA expression and indicatingthat IGFBP1 transcription is switched on oncethe progesterone block has been lost. This has implicationsin cows with a delayed post-ovulatory rise inprogesterone in which the timing of this IGFBP1 upregulationwould be shifted effecting IGF bio-availability.The embryo may further increase the availability ofIGF1 and ⁄ or IGF2 by suppressing the expression of theinhibitory IGFBP2 and IGFBP3.Luteal Inadequacy: Consequences and CausesThe timing of the post-ovulatory progesterone rise iscritical to maintaining the appropriate synchronybetween the ovary-endometrium and embryo and anyluteal inadequacy has dramatic effects. For example,Mann and Lamming (2001) demonstrated that as littleas one day delay in the rise in post-ovulatory progesteronesignificantly reduced the subsequent developmentof the embryo. Similarly, Garrett et al. (1988) showedthat supplementation with progesterone on day 1 to day4 increased embryo development. More recently, Mannet al. (2006) demonstrated that early progesteronesupplementation from day 5 to day 9, but not latersupplementation from day 12 to day 16, increased bothtrophoblastic length fivefold and uterine IFNT concentrations.Pre-ovulatory follicleWhile the consequences of luteal inadequacy on embryonicdevelopment are well-characterized, the underlyingcause of this aberrant luteal function is poorly understood.A major limitation to investigating the aetiologyhas been the lack of a robust, physiological model inwhich, from the follicular phase, it can be predictedwhether the progesterone rise would be delayed ornormal. We have recently developed such a model bymanipulating the dynamics of the follicular phase byinducing luteolysis in the presence of either a large(>10 mm) or a small (30 h afteroestrus) also results in post-ovulatory luteal inadequacy(Mann and Lamming 2001; Kaim et al. 2003). Usingour model, with detailed endocrinology and ultrasonographicmonitoring of ovarian function, we found noevidence that delayed ovulation per se (LH surge toovulation time) resulted in a delayed rise in plasma postovulatoryprogesterone (Robinson et al. 2005).Luteal development, luteotrophic support andsteroidogenic capacityThe rates of luteal growth and angiogenesis are such thatthey are only equalled by the fastest growing tumours.This enables the CL to grow from 0.5 g immediatelypost-ovulation to >5 g within 10 days (Reynolds andRedmer 1999). Our group in two independent studies hasshown that the weight of CL is highly correlated withplasma progesterone concentrations on day 5 postoestrus(Robinson et al. 2006b; Green et al. 2007).However, this relationship is reduced by day 8 andcompletely lost by day 16 (Robinson et al. 2006b). Thus,it would appear that the rate of luteal development (e.g.compactness, luteal hypertrophy) influences luteal functionrather than size per se. Other potential causes ofluteal inadequacy were insufficient luteotrophic support(e.g. number of LH pulses, basal LH and LH pulseamplitude) and aberrant steroidogenic capacity (numberof small ⁄ large luteal cells, in vitro progesterone productionunder basal or LH-stimulated conditions). Wefound that none of these factors are associated withluteal inadequacy (Robinson et al. 2006b).AngiogenesisIn order to meet these demands, the growth of bloodvessels and establishment of a blood supply (angiogen-Ó 2008 The Authors. Journal compilation Ó 2008 Blackwell Verlag