Intrauterine growth retardation (IUGR), defined as impaired growth and development of the mammalian embryo/fetus or its organs during pregnancy, is a major concern in domestic animal production. Fetal growth restriction reduces neonatal survival, has a permanent stunting effect on postnatal growth and the efficiency of feed/forage utilization in offspring, negatively affects whole body composition and meat quality, and impairs long-term health and athletic performance. Knowledge of the underlying mechanisms has important implications for the prevention of IUGR and is crucial for enhancing the efficiency of livestock production and animal health. Fetal growth within the uterus is a complex biological event influenced by genetic, epigenetic, and environmental factors, as well as maternal maturity. These factors impact on the size and functional capacity of the placenta, uteroplacental blood flows, transfer of nutrients and oxygen from mother to fetus, conceptus nutrient availability, the endocrine milieu, and metabolic pathways. Alterations in fetal nutrition and endocrine status may result in developmental adaptations that permanently change the structure, physiology, metabolism, and postnatal growth of the offspring. Impaired placental syntheses of nitric oxide (a major vasodilator and angiogenic factor) and polyamines (key regulators of DNA and protein synthesis) may provide a unified explanation for the etiology of IUGR in response to maternal undernutrition and overnutrition. There is growing evidence that maternal nutritional status can alter the epigenetic state (stable alterations of gene expression through DNA methylation and histone modifications) of the fetal genome. This may provide a molecular mechanism for the role of maternal nutrition on fetal programming and genomic imprinting. Innovative interdisciplinary research in the areas of nutrition, reproductive physiology, and vascular biology will play an important role in designing the next generation of nutrient-balanced gestation diets and developing new tools for livestock management that will enhance the efficiency of animal production and improve animal well being.

Board-invited review: intrauterine growth retardation: implications for the animal sciences.

Theca cells function in a diverse range of necessary roles during folliculogenesis; to synthesize androgens, provide crosstalk with granulosa cells and oocytes during development, and provide structural support of the growing follicle as it progresses through the developmental stages to produce a mature and fertilizable oocyte. Thecal cells are thought to be recruited from surrounding stromal tissue by factors secreted from an activated primary follicle. The precise origin and identity of these recruiting factors are currently not clear, but it appears that thecal recruitment and/or differentiation involves not just one signal, but a complex and tightly controlled combination of multiple factors. It is clear that thecal cells are fundamental for follicular growth, providing all the androgens required by the developing follicle(s) for conversion into estrogens by the granulosa cells. Their function is enabled through the establishment of a vascular system providing communication with the pituitary axis throughout the reproductive cycle, and delivering essential nutrients to these highly active cells. During development, the majority of follicles undergo atresia, and the theca cells are often the final follicular cell type to die. For those follicles that do ovulate, the theca cells then undergo hormone-dependent differentiation into luteinized thecal cells of the corpus luteum. While the theca is an essential component of follicle development and ovulation, we do not yet fully understand the control of recruitment and function of theca cells, an important consideration since their function appears to be altered in certain causes of infertility.

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Theca: the forgotten cell of the ovarian follicle.

The rate of biopharmaceutical approvals has leveled off, but some milestones bode well for the future.

Biopharmaceutical benchmarks 2006

Problem Semen is a heterogenous and complex cell suspension in a protein-rich fluid with different functions, some of them well known, others still obscure. Method of study This paper reviews, comparatively, our current knowledge on the growing field of proteomics of the SP and its relevance in relation to the in vivo situation, for the sake of reproductive biology, diagnostics and treatment. Results Ejaculated spermatozoa, primarily bathing in cauda epididymal fluid, are (in vitro) bulky, exposed to most, if not all, secretions from the accessory sexual glands. In vivo, however, not all spermatozoa are necessarily exposed to all secretions from these glands, because sperm cohorts are delivered in differential order and bathe in seminal plasma (SP) with different concentrations of constituents, including peptides and proteins. Proteins are relevant for sperm function and relate to sperm interactions with the various environments along the female genital tract towards the oocyte vestments. Specific peptides and proteins act as signals for the female immune system to modulate sperm rejection or tolerance, perhaps even influencing the relative intrinsic fertility of the male and/or couple by attaining a status of maternal tolerance towards embryo and placental development. Conclusions Proteins of the seminal plasma have an ample panorama of action, and some appear responsible for establishing fertility.

/pdf/seminal-plasma-proteins-what-role-do-they-play-4db0nx83ki.pdf

Seminal plasma proteins: what role do they play?

Proteins started being used as pharmaceuticals in the 1920s with insulin extracted from pig pancreas. In the early 1980s, human insulin was prepared in recombinant bacteria and it is now used by all patients suffering from diabetes. Several other proteins and particularly human growth hormone are also prepared from bacteria. This success was limited by the fact that bacteria cannot synthesize complex proteins such as monoclonal antibodies or coagulation blood factors which must be matured by post-translational modifications to be active or stable in vivo. These modifications include mainly folding, cleavage, subunit association, γ-carboxylation and glycosylation. They can be fully achieved only in mammalian cells which can be cultured in fermentors at an industrial scale or used in living animals. Several transgenic animal species can produce recombinant proteins but presently two systems started being implemented. The first is milk from farm transgenic mammals which has been studied for 20 years and which allowed a protein, human antithrombin III, to receive the agreement from EMEA (European Agency for the Evaluation of Medicinal Products) to be put on the market in 2006. The second system is chicken egg white which recently became more attractive after essential improvement of the methods used to generate transgenic birds. Two monoclonal antibodies and human interferon-β1a could be recovered from chicken egg white. A broad variety of recombinant proteins were produced experimentally by these systems and a few others. This includes monoclonal antibodies, vaccines, blood factors, hormones, growth factors, cytokines, enzymes, milk proteins, collagen, fibrinogen and others. Although these tools have not yet been optimized and are still being improved, a new era in the production of recombinant pharmaceutical proteins was initiated in 1987 and became a reality in 2006. In the present review, the efficiency of the different animal systems to produce pharmaceutical proteins are described and compared to others including plants and micro-organisms.

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Production of pharmaceutical proteins by transgenic animals

https://www.cell.com/trends/biotechnology/pdf/S0167-7799(03)00190-2.pdf

Making recombinant proteins in animals – different systems, different applications

This study explored the possibility of sex-specific effects on embryonic survival in primiparous sows subjected to restricted feed intake during the last week of lactation and bred after weaning (Restrict; n = 16), compared with control sows fed close to ad libitum feed intakes (Control; n = 17). Restrict sows were in a substantial negative net energy balance at weaning, and lost 13% of estimated protein and 17% of fat mass during lactation, yet the weaning-to-oestrous interval and ovulation rate were not different between treatments. However, embryonic survival at Day 30 of gestation was lower (P < 0.05) in Restrict than Control sows, and selectively reduced the proportion of female embryos surviving (P < 0.01).A decrease in weight and crown-rump length of surviving female (P < 0.05) and male (P < 0.05) embryos was seen in Restrict litters. The mechanisms mediating this sex-specific effect on embryonic loss in feed-restricted sows are unclear. The data presented here indicate that feed-restriction during the last week of lactation in primiparous sows causes a selective decrease in survival of female embryos and limits the growth of all surviving embryos.

Nutritional restriction in lactating primiparous sows selectively affects female embryo survival and overall litter development.

Biomarkers of in vivo fertility in sperm and seminal plasma of fertile stallions.

Diets enriched in unsaturated fatty acids enhance early embryonic development in lactating Holstein cows

This study aimed to describe the abundance and localization of BMP2, BMP6, BMP15, GDF9, BMPR1A, BMPR1B, BMPR2 and TGFBR1 mRNA during pig preovulatory follicular development and to evaluate their implication in improving follicular maturity in the preovulatory period preceding the second versus first post-weaning oestrus. Oocytes, granulosa (GC) and theca cells (TC) were recovered from antral follicles of primiparous sows at day 1, 2 and 4 after weaning and at day 14, 16 and 20 of their subsequent oestrous cycle. Real-time PCR analysis revealed that with the exception of BMP6 mRNA, which was absent in GC, all genes were expressed in every cell type. Although BMP6, BMP15 and GDF9 mRNA were most abundant in the oocyte, their expression remained relatively constant during follicular development. By contrast, receptor BMPR1B and TGFBR1 expressions in the GC and TC were temporally regulated. BMPR1B mRNA abundance was positively correlated with plasma oestradiol (E2) suggesting that its regulation by oestrogen may be implicated in normal folliculogenesis. Interestingly, the increase in BMPR1B mRNA and protein abundance during the periovulatory period in GC and TC suggests a role for bone morphogenetic protein (BMP) 15 in the ovulatory process. Finally, expression of these ligands and receptors was not associated with potential differences in follicle maturity observed during the second versus first post-weaning preovulatory follicular wave. In conclusion, our results clearly demonstrate the presence of a complex signalling system within the pig follicle involving the transforming growth factor-beta superfamily and their receptors, and provide evidence to support a role for BMP15 and BMPR1B during ovulation.

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Temporal regulation of BMP2, BMP6, BMP15, GDF9, BMPR1A, BMPR1B, BMPR2 and TGFBR1 mRNA expression in the oocyte, granulosa and theca cells of developing preovulatory follicles in the pig.

Michael K. Dyck

Papers

Making recombinant proteins in animals – different systems, different applications

Nutritional restriction in lactating primiparous sows selectively affects female embryo survival and overall litter development.

Biomarkers of in vivo fertility in sperm and seminal plasma of fertile stallions.

Diets enriched in unsaturated fatty acids enhance early embryonic development in lactating Holstein cows

Temporal regulation of BMP2, BMP6, BMP15, GDF9, BMPR1A, BMPR1B, BMPR2 and TGFBR1 mRNA expression in the oocyte, granulosa and theca cells of developing preovulatory follicles in the pig.