Advances in the analyses of human and other higher eukaryotic genomes have disclosed a large fraction of the genetic material (ca 98%) which does not code for proteins. Major portion of this non-coding genome is in fact transcribed into an enormous repertoire of functional non coding RNA molecules (ncRNAs) rather than encoding any proteins. Recent fascinating and fast progress in bioinformatic, high-throughput sequencing and other biochemical approaches have fuelled rapid growth in our appreciation of the tremendous number, diversity and biological importance of these ncRNAs in the hidden layer of gene regulation both at transcriptional and post-transcriptional level. Broadly ncRNAs fall into three size classes namely, 20 nucleotides for the large family of microRNAs (miRNAs), to 25-200 nucleotides for other different families of small RNAs and finally to over thousands of nucleotides for macro ncRNAs involved in eukaryotic gene regulation. Among the ncRNAs that have revolutionized our understanding of eukaryotic gene expression, microRNAs (miRNAs) have recently been emphasized extensively with enormous potential for playing a pivotal role in disease, fertility and development. They are found to be potentially involved in various aspects of physiological regulation of reproductive tissues (testis, ovary, endometrium and oviduct), cells (sperm and oocytes) and embryonic development in addition to other body systems. Here, we review the recent work on miRNAs in details and some other small ncRNAs briefly in animal models focusing on their diverse roles in the physiology of reproductive cells and tissues together with their implications for ruminant reproductive biology.
Development of the corpus luteum (CL) in ruminants occurs in a rapid and time-dependent manner within 1 week after ovulation, with morphologic and biochemical changes in the cells of the theca interna and granulosa cells of the preovulatory follicle. These changes involve luteinisation of steroidogenic cells and angiogenesis to establish normal luteal function (progesterone secretion). The CL is composed of a large number of vascular endothelial cells, large and small steroidogenic luteal cells, smooth muscle cells, pericytes, fibrocytes and immune cells, indicating that the CL is a heterogeneous tissue. Moreover, the CL produces and secretes growth factors (fibroblast growth factor, vascular endothelial growth factor and insulin-like growth factor), vasoactive factors (nitric oxide, angiotensin II and endothelin-1), steroids (progesterone is important for its own production), oxytocin and prostaglandins (PGF2alpha and PGE2) to regulate luteal formation and development. Clearly, the main function of the CL is to produce progesterone, which is a prerequisite for survival of the embryo, implantation and maintenance of pregnancy. Inadequate luteinisation and angiogenesis during the early luteal phase results in poor progesterone secretion and causes compromised embryo development and reduced fertility. Secretion of adequate amounts of progesterone during luteal development requires "precise luteinisation" of theca and granulosa cells to form luteal cells, neovascularization, and the establishment of a blood supply (angiogenesis). PGF2alpha in the developing CL acts as a local regulator to enhance progesterone secretion directly and indirectly by stimulating angiogenic factors, VEGF and FGF2. The preceding role of PGF2alpha may explain why the developing CL does not acquire luteolytic capacity until several days following ovulation. The balance between luteotrophic and luteolytic factors as well as stimulation and inhibition of angiogenic factors during luteal formation, development and maintenance can have a profound effect on the fate of the CL.
In the current review the main fundamental biological differences in reproductive function between Bos taurus and Bos indicus cattle are discussed. Breed differences regarding puberty, estrous cycle patterns, estrous behavior, acquisition of ovulatory capacity, ovarian structures and reproductive hormones are presented. The main physiological differences that Bos indicus cattle present relative to Bos taurus cattle include: delayed age at puberty; higher circulating concentrations of hormones such as estradiol, progesterone, insulin and IGF-I, despite having smaller ovulatory follicle size and corpora lutea; greater population of small follicles and smaller size of the dominant follicle at deviation; and greater sensitivity of follicles to gonadotropins. Knowledge of the differences between Bos indicus and Bos taurus breeds help explain different management procedures and responses to hormonal treatments associated with artificial insemination, ovarian superstimulation, and in vivo and in vitro embryo production.
In the mammalian ovary there is considerable and continuous remodelling of tissue during both fetal and adult life, necessitating changes in extracellular matrix. Matrix is a diverse group of molecules varying in its composition and roles, which include regulation of growth factor activity and cell behaviour. Here we discuss four topical aspects of matrices in ovaries. (1) Our current state of knowledge of latent TGFFbeta binding proteins that can bind the extracellular matrix fibrillins. Fibrillins and latent TGFbeta binding proteins may be very important given the genetic linkage data implicating a role for fibrillin 3 in polycystic ovarian syndrome. They will almost certainly be important in the stromal compartments of the ovary by regulating TGFbeta bioactivity. (2) Follicles which have an unusual ultrastructural follicular basal lamina and poor quality oocytes. The results suggest that the use of oocytes from these follicles should be avoided in assisted reproductive technologies. (3) Evidence that expression of components of focimatrix correlates with expression of aromatase and cholesterol side-chain cleavage in granulosa cells. Focimatrix is a novel type of basal lamina associated with granulosa cells with expression beginning before deviation and continuing until ovulation. It may be involved in maturation of granulosa cells and selection of the dominant follicle. (4) Evidence is presented in support of a hypothesis that follicular fluid accumulates in follicles due to the osmotic potential of hyaluronan and versican, which are matrices produced by granulosa cells and too large to traverse the follicular antrum. These examples illustrate the diversity of matrix and foreshadow potential important discoveries involving extracellular matrix in ovaries.
Three regions of the ruminant oviduct play different roles in the progress of sperm: the uterotubal junction, isthmus, and ampulla. The uterotubal junction acts as a point of selection of sperm, requiring that sperm are progressively motile and express specific proteins in order to enter the oviduct. The isthmus stores sperm, preserving motility and viability until ovulation. Sperm are stored in the isthmus by binding to its mucosal epithelium. In bovine sperm, binding to the oviductal epithelium is promoted by proteins that are secreted by the seminal vesicles and coat the heads of sperm by associating with plasma membrane phospholipids. Putative oviductal receptors for the seminal vesicle proteins are members of the annexin protein family. Release of sperm from the storage site in the isthmus is gradual, which serves to ensure that sperm in the proper physiological state reach the oocytes at the appropriate moment and also to reduce incidence of polyspermic fertilization. The ampulla supports fertilization and may participate in guiding sperm toward the eggs. Further studies are needed to improve our understanding of the interactions between sperm and the female reproductive tract, in order to develop means to improve fertility in ruminants.
Studies of low birth weight offspring have a long history in pig science. These pigs have reduced growth potential and poor carcass quality compared to their higher birth weight littermates. In contemporary commercial sows with between 10 and 15 total pigs born/litter, between-litter differences in average birth weight appear to make the largest contribution to variation in postnatal growth performance, independent of numbers born. Low birth weight is a characteristic of a subpopulation of these sows, likely as a consequence of an imbalance between ovulation rate and uterine capacity due to ongoing selection for litter size. Based on experimental studies, we hypothesize that increased crowding at day 30 of gestation primarily affects placental development and persistent negative impacts on placental growth then affect fetal development. However, embryonic myogenic gene expression is already affected at day 30. Latent effects of metabolic state on oocyte quality and early embryonic development have also been reported. In contrast to effects of uterine crowding, the embryo is primarily affected by previous catabolism. The large body of literature on gene imprinting, and the interactions between metabolism, nutrition, and methylation state, suggest that classic imprinting mechanisms may be involved. However, the potential use of genomics, epigenomics, nutrigenomics, and proteomics to investigate these mechanisms brings new demands on experimental design and data management that present a considerable challenge to the effectiveness of future research on prenatal programming in the pig.
Critical needs for the swine industry in terms of boar fertility evaluations are validation of semen quality estimates with in vivo reproductive data; estimation of the relative fertility of boars; and elimination of sub-fertile ejaculates. Single sire matings are the best way to validate semen quality estimates with reproductive performance. Sampling about 20% of the population provides an accurate estimation of the variability among boars and should be sufficient for this purpose. In vitro tests that measure univariate characteristics of ejaculates including motility and morphology appear to be just as accurate as those that measure multivariate traits such as in vitro fertilization in terms of predicting boar fertility. Reasons for this observation may be related to how properties of sperm cells are influenced by the sow reproductive tract. Several seminal plasma proteins show strong correlations with boar fertility and hold potential for being developed into tests that can rank the relative fertility of boars. Almost 90% of the variation in boar fertility was explained when the proportion of motile and acrosome-reacted spermatozoa was combined with relative amounts of 28 kDa, pl 6.0 and 55 kDa, pl 4.5 seminal plasma proteins. Consequently, combining different complementary tests improves estimations of boar fertility. Motility estimates routinely performed in most A.I. centres are a reasonable technique for identification and elimination of sub-fertile ejaculates. However, the accuracy with which they currently are conducted within the swine industry needs improvement.