MicroRNA in ovarian function Maalouf, S. W; Liu, W. S; Pate, J. L
Cell and Tissue Research,
01/2016, Letnik:
363, Številka:
1
Journal Article, Book Review
Recenzirano
The mammalian ovary is a dynamic organ. The coordination of follicle recruitment, selection, and ovulation and the timely development and regression of the corpus luteum are essential for a ...functional ovary and fertility. Deregulation of any of these processes results in ovarian dysfunction and potential infertility. MicroRNA (miRNA) are short noncoding RNA that regulate developmental processes and time-sensitive functions. The expression of miRNA in the ovary varies with cell type, function, and stage of the estrous cycle. miRNA are involved in the formation of primordial follicles, follicular recruitment and selection, follicular atresia, oocyte-cumulus cell interaction, granulosal cell function, and luteinization. miRNA are differentially expressed in luteal cells at the various stages of the estrous cycle and during maternal recognition of pregnancy, suggesting a role in luteal development, maintenance, and regression. An understanding of the patterns of expression and functions of miRNA in the ovary will lead to novel therapeutics to treat ovarian dysfunction and improve fertility and, potentially, to the development of better contraceptives.
Natural killer (NK) cells are essential for establishment of human and rodent pregnancies. The function of these and other cytotoxic T cells (CTL) is controlled by stimulatory and inhibitory ...signaling. A role for cytotoxic cells during early pregnancy in cattle has not been described, but regulation of their function at the fetal-maternal interface is thought to be critical for conceptus survival. The hypothesis that the relative abundance of CTL and expression of inhibitory signaling molecules is increased by the conceptus during early pregnancy was tested. The proportions of lymphoid lineage cells and expression of inhibitory signaling molecules in the endometrium during early pregnancy in dairy heifers were determined using flow cytometry, immunofluorescence, and realtime PCR on days 17 and 20 of pregnancy and day 17 of the estrous cycle. Results revealed an increased percentage of NKp46+ and CD8+ cells in the uterus of pregnant heifers. Furthermore, a large percentage of uterine immune cells coexpressed these proteins. Compared to cyclic heifers, CD45+ uterine cells from pregnant heifers exhibited greater degranulation. Endometrium from pregnant heifers had greater mRNA abundance for the inhibitory molecules, CD274 and lymphocyte activating gene 3 (LAG3), and greater cytotoxic T lymphocyte-associated protein 4 (CTLA4), molecules that can interact with receptors on antigen-presenting cells and induce lymphocyte tolerance. This study demonstrates a dynamic regulation of both cytotoxic immune cells and tolerogenic molecules during the peri-implantation period that may be required to support establishment of pregnancy and placentation. Summary Sentence Pregnancy increases abundance of natural killer and cytotoxic T cells and expression of immune inhibitory molecules in the endometrium of dairy heifers during early pregnancy
Establishment of pregnancy requires interaction between the developing conceptus and the uterine mucosal immune system. Myeloid lineage cells (macrophages and dendritic cells) are key mediators of ...pregnancy in rodents and humans but relatively little is known regarding their role and distribution during early pregnancy in ruminants. We tested the hypothesis that myeloid lineage cell number, distribution, and function are altered during early pregnancy in dairy heifers. Dairy heifers were inseminated using sperm from a single bull (Day 0), and uteri and blood were collected at slaughter on Days 17 and 20 of pregnancy to investigate the response of myeloid lineage cells to the presence of a conceptus. Responses were compared to noninseminated heifers on Day 17 of the estrous cycle. Peripheral blood and uterine-derived immune cells were isolated magnetically and examined using flow cytometry. Immunohistochemical analysis was used to evaluate the spatial distribution of myeloid lineage cells in the endometrium and quantitative polymerase chain reaction was conducted to quantify abundance of mRNA transcripts associated with myeloid lineage cell function. Transcripts for major histocompatibility complex (MHC) II, cluster of differentiation (CD) 80, CD86, CD163, and indoleamine 2,3-dioxygenase (IDO) 1 were greater in endometrium of pregnant compared to cyclic heifers. Immunofluorescence analysis revealed increased labeling for MHCII and SIRPA in pregnant compared to cyclic heifers. There were approximately 50% more CD14
CD11c
cells in the peripheral circulation of pregnant compared to cyclic heifers. A greater number of myeloid lineage cells were observed during early pregnancy, and this increase was most pronounced in and around the shallow glands. Furthermore, expression of molecules associated with a tolerogenic or alternatively activated phenotype of these cells also increased in pregnant heifers. The results support the hypothesis that myeloid lineage cells with a tolerogenic phenotype are involved in establishment of pregnancy in dairy heifers.
A viable corpus luteum (CL) producing an adequate amount of progesterone is absolutely essential for establishment and maintenance of pregnancy. One function of embryonic signaling to the mother is ...to ensure that the CL is maintained. In ruminants, the secretion of uterine prostaglandin F2alpha (PGF2A) is the signal that initiates luteolysis. Despite many studies to determine if PGF2A secretion from the uterus is altered in early pregnancy, conflicting interpretations have led to controversy regarding the exact mechanisms by which maternal recognition of pregnancy is achieved. In addition to alteration of uterine prostaglandin metabolism, changes within the CL itself may facilitate the establishment of a successful pregnancy. These changes include alteration of luteal blood flow, prostaglandin metabolism, sensitivity to prostaglandin actions, increased steroidogenic capacity, significant intracellular molecular changes and modification of the immune cells that are within the CL. Whether these intraluteal changes are necessary to establish pregnancy is undetermined. The focus of this review will be to provide a brief historical perspective on the utero-ovarian relationships that regulate luteal lifespan and review current knowledge of the CL of pregnancy in sheep and cattle.
•For pregnancy to be established, the corpus luteum must be maintained.•Controversy exists regarding the mechanisms by which the CL is maintained.•There are molecular and functional changes within the CL during the establishment of pregnancy.•The changes in the CL are consistent with activation of processes that protect the CL from regression.
Clear cell carcinoma (CCC) of the ovary is the surface epithelial neoplasm most often confused with primitive germ cell tumors, particularly yolk sac tumor (YST) and dysgerminoma. OCT3/4 has proven ...to be a sensitive and relatively specific marker for the latter entity, but existing markers for YST are limited. Recent studies suggest that glypican-3 (GPC3), an oncofetal protein expressed in fetal liver and malignant tumors of hepatocytic lineage, is also expressed in germ cell tumors, particularly YST. To investigate whether GPC3 is useful in distinguishing YST from ovarian CCC, we studied the expression of GPC3 in a large series of ovarian neoplasms and compared it to the expression profiles of CK7 and alpha-fetoprotein. Tissue microarrays containing over 400 benign and malignant ovarian neoplasms, including 34 CCCs were stained with monoclonal GPC3 (clone 1G12, Biomosaics, Burlington, VT). These arrays contained a wide assortment of ovarian surface epithelial neoplasms and sex cord stromal neoplasms, as well as germ cell tumors. Full paraffin tissue sections from 32 YSTs and 10 CCCs were also assessed. All but one YST (97%), including those associated with mixed germ cell tumor were positive for GPC3, whereas all teratomas and embryonal carcinomas were negative. Both cytoplasmic and membrane staining were present in the positive cases, with no background staining. The syncytiotrophoblastic cells in the germ cell tumors and placental villi included in the arrays were also positive for GPC3. Most CCCs (83%) were completely negative for GPC3, as were 99% serous, 94% endometrioid, and 100% mucinous tumors. Five CCCs exhibited focal, moderate to strong GPC3 expression and in 2 the expression was focal and weak. All other tissues, including normal ovary were negative for GPC3. GPC3 seems to be a promising diagnostic marker for differentiating YST from ovarian CCC (P < 0.0001). Because GPC3 may be associated with alpha-fetoprotein expression, further studies are required to determine the utility of GPC3 in differentiating YST from CCC with hepatoid differentiation.
Puerto Rico has been heavily impacted by Zika virus, a mosquitoborne flavivirus that emerged in the Americas during 2015. Although most persons with Zika virus show no symptoms, the virus can cause ...neurologic and other complications, including fetal microcephaly. Local Zika virus transmission in Puerto Rico has been reported since December 2015. To prevent transfusion-associated transmission, local blood collection ceased in March 2016 but resumed in April 2016 after Zika virus screening of blood donations became available. Using data from screening of blood donations collected by the 2 largest blood centers in Puerto Rico during April 3-August 12, 2016, and assuming a 9.9-day duration of viremia, we estimated that 469,321 persons in Puerto Rico were infected during this period, for an estimated cumulative incidence of 12.9%. Results from blood donation screening during arboviral outbreaks can supplement routine clinical and surveillance data for improved targeting of prevention efforts.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Health assessment of individuals is an important aspect of monitoring endangered wildlife populations. Haematological and biochemical values are a common health assessment tool, and whilst reference ...values are well established for domestic species, they are often not available for wild animal species. This study established 31 haematological and biochemical reference intervals for golden eagle (
Aquila chrysaetos
) nestlings in Scotland, in order to improve the understanding of the species’ health and support conservation efforts. Reference intervals were created from 47 nestlings (ages 2–7.5 weeks old) across 37 nests, to date, the largest sample of wild individuals of this species and age cohort sampled for these purposes. Upper reference intervals for concentrations of lymphocytes, total protein, cholesterol, triglycerides, uric acid, and monocytes, calculated in this study, are higher than those found for adult raptors and the interval span is higher than that observed in adult raptors for concentrations of AST, albumin, eosinophil, LDH, and monocyte count. Statistically significant positive correlations were found with age and concentrations of haemoglobin, lymphocytes, serum pH, and creatine kinase, and significant negative correlations with age for concentrations of thrombocytes, heterophils, total protein, globulin, and lactate dehydrogenase. Packed cell volume was significantly higher for females than males, and concentration of calcium and eosinophils were higher for individuals in good body condition than those in moderate body condition. The reference intervals produced by this study will be of important use to the veterinary and conservation management communities and will aid the long-term monitoring of the Scottish golden eagle population health.
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