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How does luteal vasculature assist or resist corpus luteum regression?
reproductive biology 13s (2013) 18–19
Available online at www.sciencedirect.com
journal homepage: http://www.elsevier.com/locate/repbio
Refresh Session Lectures RSL1 How does luteal vasculature assist or resist corpus luteum regression? R. Meidan 1, S. Farberov 1, Y. Zalman 1, G.W. Smith 2, K. Eyal 1 1 Department of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel 2 Laboratory of Mammalian Reproductive Biology and Genomics, Michigan State University, East Lansing, United States Being a highly vascular gland the corpus luteum (CL) is a site of intense angiogenesis. In fact, CL lifespan is accompanied by an intense angiogenesis and angioregression. The short period of angiogenesis of the vascular tree (until day 5 of cycle) is followed either by maintenance during pregnancy, or controlled regression (induced by prostaglandin F2a; PG) in a non-fertile cycle. The discovery of endothelial-derived factors such as endothelin-1 and nitric oxide synthase had already associated luteal vasculature with luteolysis. Recently we compared PG-induced global gene expression profiles in refractory (Day 4) bovine CL versus PGresponsive, Day 11 CL. Interestingly, quite a few of the novel PG-regulated genes were related to angiogenesis: FGF2, pentraxin 3 (PTX3), thrombospondins (THBSs) and their cell-adhesion receptor (CD36). FGF2 is a well-known angiogenesis inducer while THBSs and PTX3 bind and inhibit FGF2 actions. PG regulated these factors in a luteal stage-dependent way – a robust increase in FGF2 mRNA and protein occurred in Day 4 CL promoting CL survival and function. Conversely, THBSs, CD36 and PTX3 were upregulated by PG specifically in Day 11 CL. VEGF mRNA decreased 4 h post-PG in both Day 4 and Day 11 CL. The resulting destabilization of blood vessels is expected to weaken the gland and reduce its hormonal output. These genes were more abundant in luteal ECs than in steroidogenic cells. Similar to its in vivo effect, PG stimulated in vitro the expression of THBSs and PTX3 genes in luteal cells. Importantly, these factors influenced the angiogenic properties of luteal ECs. While FGF2 enhanced cell migration and proliferation, THBS-1 and PTX3 inhibited FGF2 actions in luteal ECs. Collectively, these data suggest that, by tilting the balance between pro- and antiangiogenic factors, PG can potentially control the ability of the CL to resist or advance toward luteolysis. http://dx.doi.org/10.1016/j.repbio.2013.01.163 RSL2 The horse: An emerging model for human infertility research K. Smits, A. Van Soom Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium Mice have been used for many decades as the predominant model to study human infertility and embryo culture, and with good results too. However, with the advent of molecular biology tools and the development of assisted reproductive tools which are applicable to domestic species, it may be wise to reconsider alternative models for studying reproduction. In this short review we want to make a case for the horse, next to the cow, as a model for human infertility research. The similarities and dissimilarities between equine and human assisted reproduction will be listed, and arguments in favor of the horse model will be discussed. The mare is, just like the cow and the human, a monovulatory species, with a very similar endocrine profile and follicular wave phenomenon from follicle emergence until a few days before ovulation. The ovaries are very assessable in the mare and follicular development can be monitored by means of transrectal ultrasound during the cycle. Typically, women are superstimulated by hormone treatment to obtain a mean of eight to ten follicles for puncture. This is not possible in mares since they are refractory to superovulation. However, for natural cycle IVF the mare resembles the woman very well, since in both species mature oocytes can be collected about 34–36 h after hCG injection. Recovery rates of mature oocytes from the gonadotropin-stimulated dominant preovulatory follicles in mares are typically high (65–80%) using a transvaginal or a flank approach. Moreover, aging mares are, just like older women, much wanted candidates for infertility treatment and thus represent a model for this application too. The horse is unfortunately the only domestic species in which routine IVF is not repeatable at present, probably because stallion spermatozoa are difficult to hyperactivate in vitro. This does not mean that the horse is not a good model for human assisted reproduction, on the contrary. It is, apart from the mouse, the only species in which embryos are routinely produced in vitro via ICSI. The ICSI-procedure is at present being applied in 50% of cases of assisted human reproduction, and is the sole solution for severe male factor infertility. In human, about 30–50% of blastocysts can be obtained after ICSI, depending on the 1642-431X/$ – see front matter
Available online at www.sciencedirect.com
journal homepage: http://www.elsevier.com/locate/repbio
Refresh Session Lectures RSL1 How does luteal vasculature assist or resist corpus luteum regression? R. Meidan 1, S. Farberov 1, Y. Zalman 1, G.W. Smith 2, K. Eyal 1 1 Department of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel 2 Laboratory of Mammalian Reproductive Biology and Genomics, Michigan State University, East Lansing, United States Being a highly vascular gland the corpus luteum (CL) is a site of intense angiogenesis. In fact, CL lifespan is accompanied by an intense angiogenesis and angioregression. The short period of angiogenesis of the vascular tree (until day 5 of cycle) is followed either by maintenance during pregnancy, or controlled regression (induced by prostaglandin F2a; PG) in a non-fertile cycle. The discovery of endothelial-derived factors such as endothelin-1 and nitric oxide synthase had already associated luteal vasculature with luteolysis. Recently we compared PG-induced global gene expression profiles in refractory (Day 4) bovine CL versus PGresponsive, Day 11 CL. Interestingly, quite a few of the novel PG-regulated genes were related to angiogenesis: FGF2, pentraxin 3 (PTX3), thrombospondins (THBSs) and their cell-adhesion receptor (CD36). FGF2 is a well-known angiogenesis inducer while THBSs and PTX3 bind and inhibit FGF2 actions. PG regulated these factors in a luteal stage-dependent way – a robust increase in FGF2 mRNA and protein occurred in Day 4 CL promoting CL survival and function. Conversely, THBSs, CD36 and PTX3 were upregulated by PG specifically in Day 11 CL. VEGF mRNA decreased 4 h post-PG in both Day 4 and Day 11 CL. The resulting destabilization of blood vessels is expected to weaken the gland and reduce its hormonal output. These genes were more abundant in luteal ECs than in steroidogenic cells. Similar to its in vivo effect, PG stimulated in vitro the expression of THBSs and PTX3 genes in luteal cells. Importantly, these factors influenced the angiogenic properties of luteal ECs. While FGF2 enhanced cell migration and proliferation, THBS-1 and PTX3 inhibited FGF2 actions in luteal ECs. Collectively, these data suggest that, by tilting the balance between pro- and antiangiogenic factors, PG can potentially control the ability of the CL to resist or advance toward luteolysis. http://dx.doi.org/10.1016/j.repbio.2013.01.163 RSL2 The horse: An emerging model for human infertility research K. Smits, A. Van Soom Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium Mice have been used for many decades as the predominant model to study human infertility and embryo culture, and with good results too. However, with the advent of molecular biology tools and the development of assisted reproductive tools which are applicable to domestic species, it may be wise to reconsider alternative models for studying reproduction. In this short review we want to make a case for the horse, next to the cow, as a model for human infertility research. The similarities and dissimilarities between equine and human assisted reproduction will be listed, and arguments in favor of the horse model will be discussed. The mare is, just like the cow and the human, a monovulatory species, with a very similar endocrine profile and follicular wave phenomenon from follicle emergence until a few days before ovulation. The ovaries are very assessable in the mare and follicular development can be monitored by means of transrectal ultrasound during the cycle. Typically, women are superstimulated by hormone treatment to obtain a mean of eight to ten follicles for puncture. This is not possible in mares since they are refractory to superovulation. However, for natural cycle IVF the mare resembles the woman very well, since in both species mature oocytes can be collected about 34–36 h after hCG injection. Recovery rates of mature oocytes from the gonadotropin-stimulated dominant preovulatory follicles in mares are typically high (65–80%) using a transvaginal or a flank approach. Moreover, aging mares are, just like older women, much wanted candidates for infertility treatment and thus represent a model for this application too. The horse is unfortunately the only domestic species in which routine IVF is not repeatable at present, probably because stallion spermatozoa are difficult to hyperactivate in vitro. This does not mean that the horse is not a good model for human assisted reproduction, on the contrary. It is, apart from the mouse, the only species in which embryos are routinely produced in vitro via ICSI. The ICSI-procedure is at present being applied in 50% of cases of assisted human reproduction, and is the sole solution for severe male factor infertility. In human, about 30–50% of blastocysts can be obtained after ICSI, depending on the 1642-431X/$ – see front matter