DNA methylation dynamics during oocyte and embryo development and its association with environmental induced alterations

Epigenetic mechanisms are fundamental to successful gametogenesis and development. The fertilized egg undergoes global DNA demethylation to facilitate remodelling from two differentiated gametespecific states to a pluripotent embryonic state. Maintenance of appropriate levels of DNA methylation during preimplantation development is essential to embryo viability. Recent advances in epigenetic research have highlighted the susceptibility of foetal epigenetic programming to maternal health and nutritional status, particularly, at the time of conception. There is much evidence that maternal stress impacts on ovarian function, leading to compromised oocytes presented for fertilization in a suboptimal environment. Similarly, declining fertility has become a substantive issue in western countries, where it is primarily associated with high mean ages at childbearing. Thus the use of assisted reproduction technologies (ART) interventions to overcome low fertility is increasing steadily across the globe. In addition, the use of prolonged in vitro culture following the removal and storage of oocytes and/or ovarian tissue in advance of cancer treatment, or to circumvent ovarian aging, is increasing rapidly. ART is associated with compromised pre and post -natal outcomes, including premature birth, low birth weight, congenital abnormalities and elevated risk of epigenetic disorders. There is extensive evidence from studies in cattle that embryos produced by conventional ART protocols are susceptible to errors in epigenetic programming. The present review discusses the impact of intrinsic physiological status and external environments on oocyte and embryo DNA methylation with regard to data available from mouse, human and bovine models.

Embryo maternal immune interactions in cattle

Mammalian embryo implantation requires the priming of the maternal immune system, but, not the provocation. There are many examples of conditions where a disturbed or aberrant immune profile during embryo implantation leads to pregnancy loss. However, these studies are primarily associated with human and mouse species; data is generally limited for cattle and livestock. Most available information centres on the endometrial response to interferon tau (IFNT), a type I antiviral cytokine, which is the maternal recognition factor for cattle and sheep. Interferon tau secretion by the embryo and detection by the dam is critical to corpus luteum (CL) maintenance and pregnancy retention. However, the large volume of bovine endometrial and conceptual transcriptomic data highlights a broader more integral role of the maternal immune system in the establishment of pregnancy in cattle. When taken together with available immunohistochemistry and flow cytometry data from livestock, mouse, and human, a profile of immune cell involvement from ovulation to conception and placentation emerges. The key events of pregnancy establishment in cattle and the involvement of the maternal immune system will be discussed.

DNA methylation dynamics during oocyte and embryo development and its association with environmental induced alterations

Epigenetic mechanisms are fundamental to successful gametogenesis and development. The fertilized egg undergoes global DNA demethylation to facilitate remodelling from two differentiated gametespecific states to a pluripotent embryonic state. Maintenance of appropriate levels of DNA methylation during preimplantation development is essential to embryo viability. Recent advances in epigenetic research have highlighted the susceptibility of foetal epigenetic programming to maternal health and nutritional status, particularly, at the time of conception. There is much evidence that maternal stress impacts on ovarian function, leading to compromised oocytes presented for fertilization in a suboptimal environment. Similarly, declining fertility has become a substantive issue in western countries, where it is primarily associated with high mean ages at childbearing. Thus the use of assisted reproduction technologies (ART) interventions to overcome low fertility is increasing steadily across the globe. In addition, the use of prolonged in vitro culture following the removal and storage of oocytes and/or ovarian tissue in advance of cancer treatment, or to circumvent ovarian aging, is increasing rapidly. ART is associated with compromised pre and post -natal outcomes, including premature birth, low birth weight, congenital abnormalities and elevated risk of epigenetic disorders. There is extensive evidence from studies in cattle that embryos produced by conventional ART protocols are susceptible to errors in epigenetic programming. The present review discusses the impact of intrinsic physiological status and external environments on oocyte and embryo DNA methylation with regard to data available from mouse, human and bovine models.(AU)

Embryo maternal immune interactions in cattle

Mammalian embryo implantation requires the priming of the maternal immune system, but, not the provocation. There are many examples of conditions where a disturbed or aberrant immune profile during embryo implantation leads to pregnancy loss. However, these studies are primarily associated with human and mouse species; data is generally limited for cattle and livestock. Most available information centres on the endometrial response to interferon tau (IFNT), a type I antiviral cytokine, which is the maternal recognition factor for cattle and sheep. Interferon tau secretion by the embryo and detection by the dam is critical to corpus luteum (CL) maintenance and pregnancy retention. However, the large volume of bovine endometrial and conceptual transcriptomic data highlights a broader more integral role of the maternal immune system in the establishment of pregnancy in cattle. When taken together with available immunohistochemistry and flow cytometry data from livestock, mouse, and human, a profile of immune cell involvement from ovulation to conception and placentation emerges. The key events of pregnancy establishment in cattle and the involvement of the maternal immune system will be discussed.(AU)

Molecular and endocrine determinants of oocyte competence

Mammalian female gametes are stored for many years in the ovaries in an inactive state until stimulated to grow. Activation of the resting follicle is initiated by the oocyte and requires a communication mechanism between the oocyte and the surrounding granulosa cells. Key molecular and morphological events that occur during oocyte and follicle growth and maturation include the establishment of a bi-directional communication system, granulosa cell proliferation and antrum formation, nucleolus activation and initiation of oocyte transcription, establishment of the maternal imprints and completion of the m eiotic maturation. Successful accomplishment of these events furnishes the oocyte with the competency to support fertilization and to sustain early embryo development and is reflected in the molecular signatures of the oocyte and the follicular granulosa cells. The current review will consider these events and highlight the molecular and endocrine factors associated with them.

Molecular and endocrine determinants of oocyte competence

Mammalian female gametes are stored for many years in the ovaries in an inactive state until stimulated to grow. Activation of the resting follicle is initiated by the oocyte and requires a communication mechanism between the oocyte and the surrounding granulosa cells. Key molecular and morphological events that occur during oocyte and follicle growth and maturation include the establishment of a bi-directional communication system, granulosa cell proliferation and antrum formation, nucleolus activation and initiation of oocyte transcription, establishment of the maternal imprints and completion of the m eiotic maturation. Successful accomplishment of these events furnishes the oocyte with the competency to support fertilization and to sustain early embryo development and is reflected in the molecular signatures of the oocyte and the follicular granulosa cells. The current review will consider these events and highlight the molecular and endocrine factors associated with them.(AU)

Variation in the number of ovarian follicles in cattle: possible causes and consequences

Background: Antral follicle count (AFC, follicles e"3 mm in diameter) varies between 5 and 50 follicles in among Bos taurus cattle. AFC is highly repeatable within animals, and is correlated with the total number of follicles in ovaries. Cattle with low AFC have higher circulating concentrations of FSH and LH, but lower concentrations of AMH, progesterone and androgens than animals with high AFC. Review: The cause of the inherently high variation in the number of follicles is unknown but it is reasonable to speculate that maternal nutrition during gestation, at the time of ovarian development in their foetuses, may impact oogonia proliferation and thus follicle numbers postnatally. We have recently started to test this hypothesis by restricting nutrition of beef heifers to 0.6 of their maintenance energy requirements, from shortly before conception to the end of the first trimester of pregnancy (period encompassing the peak in oocyte numbers in foetuses). Results show that calves born to nutritionally restricted mothers have a 60% lower peak, minimum and mean AFC during follicular waves compared with calves born to mothers fed control diets. Interestingly these calves from restricted mothers also had higher blood pressure compared to controls. Additional studies also provide evidence to suggest that fertility may be compromised in animals with low AFC due to effects on oocytes, progesterone and the endometrium compared to animals with high AFC. To test this hypothesis we performed ovarian ultrasonography on 306 dairy cows during the first wave of follicular development 1 to 4 months post partum and recorded their reproductive performances during the breeding season; cows with a high AFC had higher pregnancy rates, shorter calving to conception intervals and received fewer services during the breeding season compared to cows with a low AFC. Conclusion: Recent studies suggest that the numbers of follicles in follicle waves, and in total in the ovaries, may now be an important consideration for further efforts to understand and manipulate fertility. Since ovarian follicle numbers are reflective of the environment during foetal development when all the organ systems are developing, altered follicle numbers may also be reflective of other developmental difference in organs that may have more profound effects on the animals health and welfare beyond effects on reproduction and fertility.