Research in animal reproduction: Quo vadimus?

Population growth and trends in food consumption are expected to result in a net food deficit and widespread loss of food security across the globe within four decades. It is generally accepted that this crisis will have to be met by increased livestock production, using less land, less water and in an environmentally sustainable fashion. As animal reproduction and reproductive efficiency are the basis of livestock production, it is essential that technological advances be made to increa se the animal-based food supply. Improvements are required in artificial insemination procedures, in embryo transfer and in transgenic animal production. Technology is evolving such that it may soon be possible to rapidly sequence genomes and transcriptomes to hasten genetic improvements, to produce gametes from stem cells, and to increase success rates in livestock transgenesis. The principal constraints at this time are on research funding and on the paucity of scientists with multidisciplinary skills. Given its livestock population, its biodiversity, and its burgeoning scientif ic expertise, Brazil is expected to be a major contributor to the resolution of food security problems in coming years.

Equine chorionic gonadotropin: an enigmatic but essential tool

Equine chorionic gonadotropin (eCG) was discovered more than 80 y ago as a factor found in circulation of the pregnant mare during the first third of gestation. It is a variant of equine luteinizing hormone (LH), differentially glycosylated by the equine trophoblast cells. It has the peculiar property of provoking both follicle-stimulating hormone (FSH) and LH activity in non-equid species. The biological basis for this dual activity is believed to be the result of promiscuity of the mammalian FSH receptors, imparting the capacity to respond to this equine LH-like hormone. The best approximation of the role of eCG in the mare is that it induces accessory corpora lutea to better support early gestation. There are numerous applications for eCG in domestic species, including induction of puberty, reversal of anestrus, superovulation and, most recently, improvement of fertility.

Equine chorionic gonadotropin: an enigmatic but essential tool

Equine chorionic gonadotropin (eCG) was discovered more than 80 y ago as a factor found in circulation of the pregnant mare during the first third of gestation. It is a variant of equine luteinizing hormone (LH), differentially glycosylated by the equine trophoblast cells. It has the peculiar property of provoking both follicle-stimulating hormone (FSH) and LH activity in non-equid species. The biological basis for this dual activity is believed to be the result of promiscuity of the mammalian FSH receptors, imparting the capacity to respond to this equine LH-like hormone. The best approximation of the role of eCG in the mare is that it induces accessory corpora lutea to better support early gestation. There are numerous applications for eCG in domestic species, including induction of puberty, reversal of anestrus, superovulation and, most recently, improvement of fertility.(AU)

Research in animal reproduction: Quo vadimus?

Population growth and trends in food consumption are expected to result in a net food deficit and widespread loss of food security across the globe within four decades. It is generally accepted that this crisis will have to be met by increased livestock production, using less land, less water and in an environmentally sustainable fashion. As animal reproduction and reproductive efficiency are the basis of livestock production, it is essential that technological advances be made to increa se the animal-based food supply. Improvements are required in artificial insemination procedures, in embryo transfer and in transgenic animal production. Technology is evolving such that it may soon be possible to rapidly sequence genomes and transcriptomes to hasten genetic improvements, to produce gametes from stem cells, and to increase success rates in livestock transgenesis. The principal constraints at this time are on research funding and on the paucity of scientists with multidisciplinary skills. Given its livestock population, its biodiversity, and its burgeoning scientif ic expertise, Brazil is expected to be a major contributor to the resolution of food security problems in coming years.(AU)

Orphan nuclear receptor regulation of reproduction

Orphan nuclear receptors, those without known ligands, were discovered because of their structural similarity to the ligand-driven steroid and thyroid receptors. Since their characterization, many of the orphan receptors have been adopted, i.e., ligands, usually lipids or derived lipids, have been discovered. The orphan receptors are transcriptional regulators, functioning in the reproductive context to upregulate or suppress gene expression. By this means, the orphan receptors regulate a plethora of reproductive events. In the majority of cases, the effects are stimulatory, indeed, members of the NR2 family promote Leydig cell differentiation and testicular steroidogenesis, while those of the NR4 family regulate early gestation and placental formation. The NR5 family has two members, steroidogenic factor-1 (SF-1, NR5A1) and liver receptor homolog-1 (LRH-1, NR5A2). These receptors interact with the same DNA sequence and are believed to be constitutive transcription factors. Their effects are modulated by the repressive effects of the NR0 family of orphan receptors that comprise the short heterodimeric partner (SHP, NR0B2) and dosage-sensitive sex reversal adrenal hypoplasia congenital region on the X chromosome, gene 1 (DAX1, NROB1). SHP and DAX1 inhibit the interaction of LRH-1 and SF-1 with coactivators, thereby reducing their constitutive transcriptional effects. Overall, the orphan nuclear receptors are essential regulators of reproductive function in mammals.

Orphan nuclear receptor regulation of reproduction

Orphan nuclear receptors, those without known ligands, were discovered because of their structural similarity to the ligand-driven steroid and thyroid receptors. Since their characterization, many of the orphan receptors have been adopted, i.e., ligands, usually lipids or derived lipids, have been discovered. The orphan receptors are transcriptional regulators, functioning in the reproductive context to upregulate or suppress gene expression. By this means, the orphan receptors regulate a plethora of reproductive events. In the majority of cases, the effects are stimulatory, indeed, members of the NR2 family promote Leydig cell differentiation and testicular steroidogenesis, while those of the NR4 family regulate early gestation and placental formation. The NR5 family has two members, steroidogenic factor-1 (SF-1, NR5A1) and liver receptor homolog-1 (LRH-1, NR5A2). These receptors interact with the same DNA sequence and are believed to be constitutive transcription factors. Their effects are modulated by the repressive effects of the NR0 family of orphan receptors that comprise the short heterodimeric partner (SHP, NR0B2) and dosage-sensitive sex reversal adrenal hypoplasia congenital region on the X chromosome, gene 1 (DAX1, NROB1). SHP and DAX1 inhibit the interaction of LRH-1 and SF-1 with coactivators, thereby reducing their constitutive transcriptional effects. Overall, the orphan nuclear receptors are essential regulators of reproductive function in mammals.(AU)

Epigenetic anomalies associated with prenatal survival and neonatal morbidity in cloned calves

Many of the developmental anomalies observed in cloned animals are related to fetal and placental overgrowth, a phenomenon known as the “large offspring syndrome” (LOS) in ruminants. It has been hypothesized that the epigenetic control of imprinted genes, i.e. genes that are expressed in a parental-specific manner, is at the root of LOS. Our recent research has focused on understanding the epigenetic alterations to imprinted genes that are associated with assisted reproductive technologies (ART), such as early embryo in vitro culture (IVC) and somatic cell nuclear transfer (SCNT) in cattle. We have searched and identified single nucleotide polymorphisms in Bos indicus DNA useful for analysis of parental-specific alleles and their respective transcripts in tissues from hybrid embryos derived by crossing Bos indicus and Bos taurus cattle. Due to the frequency of placental anomalies in SCNT and in some IVC gestations, our initial studies focused on genes known to be necessary for trophoblast proliferation (Mammalian Achaete Scute-like Homologue 2; ASCL2) and differentiation (Heart and neural crest cell derivative 1; HAND1). ASCL2 was bi-allelically expressed prior to implantation but paternally silenced after implantation. At day 17, SCNT embryos showed more abundant ASCL2 and less abundant HAND1 transcripts. After implantation, SCNT fetal cotyledons displayed higher ASCL2 and HAND1 than AI and IVC tissues. To further investigate epigenetic anomalies, we analyzed the differentially methylated regions of other imprinted genes in cattle, i.e. SNRPN, H19 and the IGF2R. Compared with the patterns observed in vivo (AI), we observed a generalized hypomethylation of the imprinted allele and the bi-allelic expression of embryos produced by SCNT...

Epigenetic anomalies associated with prenatal survival and neonatal morbidity in cloned calves

Many of the developmental anomalies observed in cloned animals are related to fetal and placental overgrowth, a phenomenon known as the “large offspring syndrome” (LOS) in ruminants. It has been hypothesized that the epigenetic control of imprinted genes, i.e. genes that are expressed in a parental-specific manner, is at the root of LOS. Our recent research has focused on understanding the epigenetic alterations to imprinted genes that are associated with assisted reproductive technologies (ART), such as early embryo in vitro culture (IVC) and somatic cell nuclear transfer (SCNT) in cattle. We have searched and identified single nucleotide polymorphisms in Bos indicus DNA useful for analysis of parental-specific alleles and their respective transcripts in tissues from hybrid embryos derived by crossing Bos indicus and Bos taurus cattle. Due to the frequency of placental anomalies in SCNT and in some IVC gestations, our initial studies focused on genes known to be necessary for trophoblast proliferation (Mammalian Achaete Scute-like Homologue 2; ASCL2) and differentiation (Heart and neural crest cell derivative 1; HAND1). ASCL2 was bi-allelically expressed prior to implantation but paternally silenced after implantation. At day 17, SCNT embryos showed more abundant ASCL2 and less abundant HAND1 transcripts. After implantation, SCNT fetal cotyledons displayed higher ASCL2 and HAND1 than AI and IVC tissues. To further investigate epigenetic anomalies, we analyzed the differentially methylated regions of other imprinted genes in cattle, i.e. SNRPN, H19 and the IGF2R. Compared with the patterns observed in vivo (AI), we observed a generalized hypomethylation of the imprinted allele and the bi-allelic expression of embryos produced by SCNT...(AU)