Society of Reproduction and Fertility supplement最新文献

Activation of its genome is amongst the essential task the embryo has to undertake following fertilization of the egg. In animal and plants, this activation follows a period of transcriptional silence, which is made necessary by the requirement for an almost complete and functional reprogramming of the DNA coming from both gametes. The process by which DNA is silenced, reprogrammed and reactivated is not fully understood yet but progresses are being made, especially with the help of genomic tools. This review will focus on the recent discoveries made in different animal models and more specifically on the efforts made to further characterize the event of maternal to embryonic transition in bovine embryos.

Despite apparent progress in reproductive technology as applied to wild ruminants, the success achieved in terms of the number of offspring that become healthy adults has remained low. Difficulties often arise through a lack of knowledge regarding appropriate cryopreservation techniques, and indeed through a lack of detailed information on the reproductive physiology of the species in question. The Spanish ibex (Capra pyrenaica) is a wild caprid found exclusively in the mountains of Iberia; only two of the original four subspecies still exist. Great efforts need to be made to preserve this species. The endocrine and environmental mechanisms that control its seasonal reproduction need to be properly understood, reproductive technologies (particularly the cryopreservation of gametes) optimised, and genetic resource banks developed. The experience obtained with the Spanish ibex may be useful in ex situ conservation strategies designed to preserve other threatened Mediterranean wild ruminants.

The New Zealand (NZ) economy and its dairy industry are sensitive to global consumer perception of farming practices used to generate milk products because milk exports account for > 25% of national export earnings and > 90% of milk produced is exported as products. Astute management of product image and market risk is, therefore, important for the viability of the industry and country. More than 95% of milk produced in NZ comes from strictly seasonal, pasture-based systems, with associated constraints on reproductive performance. Increasing herd sizes, operational changes and genetic selection priorities have further challenged dairy farmers to achieve optimal levels of herd fertility. Reproductive management practices have developed to address the need to maintain a 365-day inter-calving interval, essentially through maximizing the number of cyclic cows during the breeding period and minimizing the duration of the seasonal calving period. Aspects of the hormonal interventions developed and routinely used to achieve these objectives have been the subject of product quality and market risk concerns forcing the industry to explore alternative ways of achieving reproductive performance goals. One approach has been to exploit the inherently high level of fertility in NZ dairy herds. This approach has seen the inclusion of fertility-related traits in the national genetic evaluation system to prevent further decline in genetic fertility. More recently, a nationally coordinated extension program has been adopted to support farmers and their advisors to identify, prioritize and improve on key management areas for incremental gains in herd reproductive performance. Advances in automation and bio-sensing are yet to make a significant impact, but remain potentially valuable additions in supporting the dairy farmer to manage the areas having the largest effects on reproductive performance.

Poor reproductive efficiency is a worldwide problem affecting the dairy industry. There is substantial evidence for an association between high milk production and lower conception rates observed in cows compared to heifers. However, whether the decline in fertility is due directly to the level of milk production or other factors associated with lactation is unclear. There are various checkpoints along the developmental axis which could, in part, contribute to reduced fertility including suboptimal follicle development associated with poor oestrus exhibition, suboptimal oocyte quality, altered sperm transport and fertilization and/or a suboptimal reproductive tract environment incapable of supporting normal embryo development. The challenge is deciphering where the major problems lie. Evidence for the relative contributions of oocyte quality, embryo quality and the reproductive tract environment is discussed in this paper.

The establishment and maintenance of pregnancy in lactating dairy cows is a complex biological event that is influenced by a multitude of factors, from the reproductive biology of the cow to managerial aspects of the dairy farm. It is often mentioned in the scientific literature that fertility in dairy cows has declined concurrent with major advances in milk production. Some of this decline is attributed to the negative genetic correlation between milk production and reproduction. In the United States, yearly production per cow has increased steadily at a rate of 1.3% in the last decade and it is likely that this trend will continue in the years to come. At this rate, the average cow in the United States will be producing over 14 tons of milk per year in 2050 and technologies will have to be developed to allow these cows to reproduce to maintain the sustainability of dairy production. Despite high production, it is not uncommon for dairy herds with rolling herd averages for milk yield above 11,000 kg to overcome the challenges of reproduction and obtain satisfactory reproductive performance. Among other things, those herds have been able to mitigate some of the mechanisms that suppress reproduction in dairy cows such as extended postpartum anovulatory period, poor estrous detection, low pregnancy per insemination and, to a lesser extent, the high pregnancy loss. The success of those farms comes from an integrated approach to fertility that includes adequate cow comfort, elaborated transition cow management and nutrition, aggressive postpartum health monitoring program with preventative and curative measures to mitigate the negative effects of diseases on reproduction, and a sound reproductive program that includes manipulation of the ovarian cycle to allow for increased insemination rate. More recently, introduction of fertility traits in selection programs have created new opportunities for improved reproduction without neglecting economically important production traits.

Estrous synchronization and timed ovulation programs that permit AI at a predetermined time (timed AI) rather than as determined by detection of spontaneous estrus are requisite for increased adoption of AI in the beef cattle industry. In the past two decades, significant progress has been achieved in developing programs that synchronize ovulation to address this need. While this progress has been driven by a multitude of fundamental discoveries in reproductive biology, the greatest impact in the past two decades has been the result of enhanced understanding of the pattern of ovarian follicle growth in cattle and development of technologies to coordinate growth and ovulation of the dominant follicle. At present, estrous synchronization programs that result in acceptable timed AI pregnancy rates are available for beef cattle. The capacity to control growth of the dominant follicle and evaluate the impact of various approaches on fertility has resulted in greater understanding of the factors that influence maturity of ovulatory follicles. Modifications to the standard industry breeding programs, with the aim of lengthening and/or increasing the gonadotropic stimulus and estradiol production by preovulatory follicles, have been shown to substantially increase timed AI pregnancy rate in beef cattle. Associations between characteristics of follicular development and fertility have surfaced from application of estrous and ovulation synchronization technologies and led to investigation of the fundamental mechanisms that underlie these relationships.

The mechanisms regulating development of a single (dominant) follicle capable of ovulation during each follicular wave in cattle and atresia of remaining follicles (dominant follicle selection) are not well understood. FSH and IGF1 are known regulators of follicle growth and granulosa cell estradiol production during follicular waves. Recent evidence indicates cocaine and amphetamine regulated transcript (CARTPT), with intraovarian expression only in single-ovulating species, is a novel regulator of follicular development. The mature CARTPT peptide (CART) is a potent negative regulator of FSH and IGF1 action on granulosa cells in vitro and can inhibit follicular estradiol production in vivo. Follicular fluid CART concentrations in healthy follicles decrease after dominant follicle selection and CARTPT mRNA is lower in healthy versus atretic follicles collected prior to and early after initiation of follicle dominance, suggestive of a regulatory role in the selection process. The inhibitory actions of CART on FSH signaling and estradiol production are dependent on the G(o/i)-subclass of inhibitory G proteins and linked to multiple components of the FSH signal transduction pathway resulting in reduced CYP19A1 mRNA and estradiol production. Evidence to date supports a potential important functional role for CART in regulation of dominant follicle selection and the species-specific ovulatory quota in monotocous species.

Ruminants have been utilised extensively to investigate the developmental origins of health and disease, with the sheep serving as the model species of choice to complement dietary studies in the rat and mouse. Surprisingly few studies, however, have investigated delayed effects of maternal undernutrition during pregnancy on adult offspring health and a consistent phenotype, together with underlying mechanistic pathways, has not emerged. Nevertheless, when broad consideration is given to all studies with ruminants it is apparent that interventions that are initiated very early in gestation, and/or prior to conception, lead to greater effects on adult physiology than those that are specifically targeted to late gestation. Effects induced following dietary interventions at the earliest stages of mammalian development have been shown to arise as a consequence of alterations to key epigenetic processes that occur in germ cells and pluripotent embryonic cells. Currently, our understanding of epigenetic programming in the germline is greatest for the mouse, and is considered in detail in this article together with what is known in ruminants. This species imbalance, however, looks set to change as fully annotated genomic maps are developed for domesticated large animal species, and with the advent of 'next-generation' DNA sequencing technologies that have the power to globally map the epigenome at single-base-pair resolution. These developments would help to address such issues as sexually dimorphic epigenetic alterations to DNA methylation that have been found to arise following dietary restrictions during the peri-conceptional period, the effects of paternal nutritional status on epigenetic programming through the germline, and transgenerational studies where, in future, greater emphasis in domesticated ruminants should be placed on traits of agricultural importance.

The ovine conceptus releases interferon-tau (IFNT), which prevents upregulation of the endometrial estrogen receptor (ESR1) and, consequently, oxytocin receptor (OXTR), thereby disrupting pulsatile release of prostaglandin F2alpha (PGF) in response to oxytocin. IFNT, through paracrine action on the endometrium, protects the corpus luteum (CL) during maternal recognition of pregnancy. Pregnancy also induces IFN stimulated genes (ISGs) in peripheral blood mononuclear cells (PBMCs), which is interpreted to reflect a "prompted" antiviral and immune cell response peripherally in ruminants. IFNT was recently demonstrated to be released from the uterus in amounts of 200 microg (2 x 10(7) U)/24 h via the uterine vein and to induce ISGs in the CL during maternal recognition of pregnancy. Delivery of recombinant ovine (ro) IFNT into the uterine vein in a location that is upstream of the utero-ovarian plexus from Day 10 to 17 maintained serum progesterone concentrations and extended normal 16-17 d estrous cycles to beyond 32 d. It is concluded from these studies that IFNT is released into the uterine vein and initiates a peripheral antiviral response to protect pregnancy from maternal viral infection. It also may have endocrine action through inducing luteal resistance to PGF and longer-term survival of the CL and maintenance of pregnancy.

Circannual clocks drive rhythms in reproduction and many other seasonal characteristics but the underlying control of these long-term oscillators remains a mystery. Now, we propose that circannual timing involves mechanisms that are integral to the ontogenetic life-history programme where annual transitions are generated by cell birth, death and tissue regeneration throughout the life cycle--the histogenesis hypothesis. The intrinsic cycle is then timed by cues from the environment. The concept is that in specific sites in the brain, pituitary and peripheral tissues, residual populations of progenitor cells (adult stem cells) synchronously initiate a phase of cell division to begin a cycle. The progeny cells then proliferate, migrate and differentiate, providing the substrate that drives physiological change over long time-spans (e.g. summer/winter); cell death may be required to trigger the next cycle. We have begun to characterise such a tissue-based timer in our Soay sheep model focusing on the pars tuberalis (PT) of the pituitary gland and the sub-ventricular zone of the mediobasal hypothalamus (MBH) as potential circannual pacemakers. The PT is of special interest because it is a melatonin-responsive tissue containing undifferentiated cells, strategically located at the gateway between the brain and pituitary gland. The PT also governs long-photoperiod activation of thyroid hormone dependant processes in the MBH required for neurogenesis. In sheep, exposure to long photoperiod markedly activates BrDU-labelled cell proliferation in the PT and MBH, and acts to entrain the circannual reproductive cycle. Variation in expression and co-ordination of multiple tissue timers may explain species differences in circannual rhythmicity. This paper is dedicated to the memory of Ebo Gwinner.