Identification of novel genes associated with dominant follicle development in cattle

2007 ◽  
Vol 19 (8) ◽  
pp. 967 ◽  
Author(s):  
Anna E. Zielak ◽  
Niamh Forde ◽  
Stephan D. E. Park ◽  
Fiona Doohan ◽  
Paul M. Coussens ◽  
...  

Follicle development is regulated by the interaction of endocrine and intrafollicular factors, as well as by numerous intracellular pathways, which involves the transcription of new genes, although not all are known. The aim of the present study was to determine the expression of a set of unknown genes identified by bovine cDNA microarray analysis in theca and granulosa cells of dominant and subordinate follicles, collected at a single stage of the first follicular wave using quantitative real-time polymerase chain reaction. Differences were further examined at three stages of the follicular wave (emergence, selection and dominance) and bioinformatics tools were used to identify these originally unknown sequences. The suggested name function and proposed role for the novel genes identified are as follows: MRPL41 and VDAC2, involved in apoptosis (dominant follicle development); TBC1D1 stimulates cell differentiation (growth associated with dominant follicle selection and development); STX7, promotes phagocytosis of cells (subordinate follicle regression); and SPC22 and EHD3, intracellular signalling (subordinate follicle regression). In conclusion, we have identified six novel genes that have not been described previously in ovarian follicles that are dynamically regulated during dominant follicle development and presumably help mediate intracellular signalling, cell differentiation, apoptosis and phagocytosis, events critical to follicular development.

2015 ◽  
Vol 27 (1) ◽  
pp. 178
Author(s):  
K. M. Lemes ◽  
L. A. Silva ◽  
E. C. C. Celeghini ◽  
M. A. Alonso ◽  
G. Pugliesi ◽  
...  

The postpartum period is characterised by the rapid uterine involution process and return of ovarian activity (foal heat), resulting in a fertile oestrus in most of the mares. However, the follicular development and selection processes during this period are not completely known in horses. We aimed to study the characteristics of follicular growth and vascular perfusion in the ovary during the early postpartum period in mares that demonstrated oestrous behaviour and had early (<10 days) or late (≥10 days) ovulation. Ten mares were scanned daily from the first day postpartum (Day 1) until the day of the first postpartum ovulation (Day 0). The animals were split in the early (n = 3) and late (n = 7) ovulation groups (averaged interval between parturition and ovulation: 8.0 ± 0.0 and 14.7 ± 1.2 days, respectively). For ultrasound exams a Duplex B-mode and colour Doppler instrument (M5VET®, Mindray, Shenzhen, China) was used with a multifrequency linear probe. Data were analysed for the main effects of group, day, and their interaction using the PROC MIXED procedure of SAS software (version 9.3, SAS Institute Inc., Cary, NC, USA). For the follicular growth, no difference (P > 0.05) was detected between the groups when the data were analysed for the days relative to ovulation (from Day 7 to Day 1). However, the dominant follicle was larger (P < 0.05) in the early-ovulated group (37.2 ± 1.6 v. 21.9 ± 1.1) in all days during early postpartum (Day 1 to Day 7). The number of follicles with >25 mm diameter was also greater (P < 0.05) in the early-ovulated group (1.1 ± 0.1 v. 0.1 ± 0.1) during the first 3 days postpartum. In addition, the late-ovulated mares showed greater number of follicles with 20–25 mm during Day 4 to Day 7 (2.0 ± 0.2 v. 0.7 ± 0.1). For the blood flow characteristics, no difference (P > 0.05) was detected in the coloured signals of blood flows in the follicular wall of the dominant follicle or in the ovarian pedicle ipsilateral to the largest follicle. Therefore, the characteristics of the follicle growth on the preceding days of ovulation were similar between the early- and late-ovulated mares and consistent with the follicular dynamics expected in non-pregnant and non-lactating mares. However, when the data were analysed for the days relative to parturition, a greater follicle development was present in mares that ovulate earlier during the postpartum period (<10 days). In conclusion, the results suggest that important events may occur previous to the parturition, resulting in an early follicle development, mainly in those mares that show heat signs and ovulate within 10 days postpartum. Research was supported by FAPESP process number 2010/10692-9 and CNPq process number 135954/2011-8.


2007 ◽  
Vol 19 (1) ◽  
pp. 242
Author(s):  
C. Kawashima ◽  
N. Sudo ◽  
C. Amaya Montoya ◽  
E. Kaneko ◽  
M. Matsui ◽  
...  

Recent studies have shown that IGF-1 is a crucial factor for ovarian follicular development in mammals. In postpartum (pp) dairy cows, plasma IGF-1 and estradiol (E2) levels in ovulatory cows at the first follicular wave pp are higher than in anovulatory cows. However, the plasma IGF-1 profile in an ovulatory or anovulatory dominant follicle (DF), which have different E2 production, at the first follicular wave pp have not yet been elucidated. Thus, we investigated the changing profile of plasma IGF-1 levels during first follicular wave pp. In 22 multiparous Holstein cows, blood samples were obtained 2 times/week from 4 weeks prepartum to 3 weeks pp, and the first follicular wave was monitored by ultrasound 2 times/week from 7 days pp to ovulatory phase. Detailed IGF-1 profiles in blood were determined during DF growth and maturation 4 times/day from 10 days pp to 7 days after the first ovulation in 5 ovulatory cows and to 20 days pp in 4 anovulatory cows; the data were analyzed by repeated measures ANOVA, and Student&apos;s t-test. There was no interaction between groups and time within the prepartum or the pp period. The ovulatory cows (n = 13/22) with an estrogen-active dominant (EAD: high plasma E2 level with peak) follicle showed higher IGF-1 levels than anovulatory cows (n = 9/22) with an estrogen-inactive dominant (EID: low plasma E2 level without peak) follicle during the prepartum (117 � 8 vs. 91 � 5 ng mL-1; P &lt; 0.05) and the pp (91 � 4 vs. 64 � 4 ng mL-1; P &lt; 0.001) period. Especially noteworthy, during the first follicular wave pp in ovulatory cows, the plasma IGF-1 levels were maintained at a high level until E2 levels increased, followed by an LH surge. We observed that the EAD follicle in ovulatory cows ovulated. To further examine the IGF-1 system in the intra-follicular environment, we used the EAD and EID follicles from ovaries of dairy cows obtained at a slaughterhouse. The EAD and EID follicles were classified on the basis of follicle diameter and E2 concentrations in follicular fluid (FF). The significant differences of factors between EAD and EID were analyzed by Student&apos;s t-test. The expression of IGF-1 mRNA was not detected in follicular cells in either EAD and EID, suggesting that IGF-1 in FF is mainly derived from liver. The free IGF-1 levels in FF in EAD (4.8 � 0.5 ng mL-1) were higher than those in EID (2.7 � 0.1 ng mL-1; P &lt; 0.05). In addition, the expression of type 1 IGF receptor (IGFR-1) mRNA in EAD was higher than hat in EID (P &lt; 0.0001). From the results of the present study, it is apparent that the EAD follicle during the first follicular wave pp in ovulatory cows sufficiently expressed IGFR-1, and a liver-derived IGF-1 stimulates E2 production in the follicle to ovulate. In conclusion, our data suggest that a high concentration of IGF-1, secreted from the liver, during the peripartum period may be one of important factors for the appearance of an ovulatory follicle during the first follicular wave pp cows.


Reproduction ◽  
2002 ◽  
pp. 531-541 ◽  
Author(s):  
EJ Austin ◽  
M Mihm ◽  
AC Evans ◽  
JL Ireland ◽  
JJ Ireland ◽  
...  

Antral follicle development in cattle is initially FSH dependent and then LH dependent. The aim of the present study was to determine the effects of oestradiol- and progesterone-induced suppression of FSH and LH on growth and differentiation of first wave follicles. Cyclic heifers (n = 45, n = 6-10 per group) received the following i.m. injections or treatments beginning 30 h after oestrus: (i) saline (controls); (ii) 0.75 mg oestradiol benzoate (ODB); (iii) insertion of a progesterone-releasing intravaginal device (PRID) for 42 h (progesterone); (iv) 0.75 mg oestradiol benzoate plus PRID (ODB plus progesterone); (v) 0.75 mg ODB plus injection of 1 mg Ovagen(TM) at 33, 39 and 45 h after onset of oestrus (ODB plus FSH). In Expt 1, follicle development was monitored by ovarian ultrasonography once a day. In Expt 2, heifers were ovariectomized. Emergence of the first follicle wave and dominant follicle selection were delayed in ODB plus progesterone-treated heifers compared with controls. Interval to nadir FSH concentration was shorter in ODB-, progesterone- and ODB plus progesterone-treated heifers compared with controls. Frequency of LH pulses was unaffected in ODB- or ODB plus FSH-treated heifers, decreased in progesterone-treated heifers and further decreased in ODB plus progesterone-treated heifers. Intrafollicular oestradiol concentrations were lower in the largest follicle from ODB plus progesterone-treated heifers compared with control (66 h) heifers, but follicle diameter and concentrations of insulin-like growth factor binding proteins (IGFBPs) and inhibin forms were unaffected. Treatment with ODB decreased follicular oestradiol concentration in smaller follicles in the cohort. It is concluded that growing cohort follicles are uniformly responsive to increased FSH concentration but differentially responsive to suppressed FSH and LH release, which is consistent with an LH-mediated survival advantage of the largest follicle in the cohort before cessation of the growth of remaining follicles in the cohort occurs.


2000 ◽  
Vol 85 (9) ◽  
pp. 3319-3330
Author(s):  
Alan L. Schneyer ◽  
Toshihiro Fujiwara ◽  
Janis Fox ◽  
Corrine K. Welt ◽  
Judith Adams ◽  
...  

Abstract Previous studies of normal human ovaries suggest that inhibins, activins, and follistatin (FS) are produced in a stage-specific pattern indicative of intraovarian, autocrine/paracrine roles in regulating follicle development. However, these studies relied largely on surgical specimens and thus include little information about the menstrual cycle stage or dominant follicle status at the time follicles or ovaries were obtained. The purpose of this study was to 1) determine the pattern of intrafollicular hormone biosynthesis across antral follicle development in normal women, 2) compare hormone concentrations in dominant and nondominant follicles from the same ovary, and 3) examine the relationship between dominant follicle hormone content and circulating hormone levels. Intrafollicular estradiol, progesterone, and inhibin A concentrations increased significantly with follicle size or maturity, whereas significant inverse relationships were observed for androstenedione and the androstenedione/estradiol (A:E) ratio. In contrast, neither inhibin B, activin A, nor free FS varied consistently with size or maturity. Estradiol, progesterone, and inhibin A levels and A:E ratio were significantly lower in nondominant follicles compared to the dominant follicle aspirated from the same ovary. Although intrafollicular and serum concentrations of each hormone followed the same general pattern as follicles develop, the human follicular fluid/serum gradients changed during the follicular phase and were different for estradiol and inhibin A, suggesting the presence of stage-specific differences in pharmacodynamics. These results are consistent with the hypothesis that the orderly transition from an activin-dominant to an inhibin A/FS-dominant microenvironment is critical for dominant follicle development.


Reproduction ◽  
2006 ◽  
Vol 132 (3) ◽  
pp. 365-377 ◽  
Author(s):  
M A Beg ◽  
O J Ginther

The eminent event in follicle selection during a follicular wave in monovular species is diameter deviation, wherein one follicle continues to grow (developing dominant) and other follicles (subordinates) begin to regress. In cattle, the IGF system, oestradiol and LH receptors are involved in the intrafollicular events initiating deviation as indicated by the following: (1) concentrations of free IGF-I and oestradiol in the follicular fluid and number of LH receptors in the follicular wall increase more dramatically in the future dominant follicle than in the future subordinate follicles before the beginning of deviation and (2) ablation of the largest follicle (LF) or injection of recombinant human IGF (rhIGF)-I into the second LF at the expected beginning of deviation increases the concentrations of oestradiol in second LF before the expected beginning of deviation between second LF and third LF. In horses, an increase in free IGF-I, oestradiol, inhibin-A and activin-A is greater in the future dominant follicle than in other follicles before the beginning of deviation. However, free IGF-I is the only one of these four factors needed for the initiation of deviation in horses as indicated by the following: (1) ablation of LF at the expected beginning of deviation increases the concentrations of free IGF-I in second LF before the beginning of deviation between second LF and third LF but does not increase the other factors; (2) injection of rhIGF-I into second LF at the expected beginning of deviation causes second LF to continue to grow and become a codominant follicle and (3) injection of IGF-binding protein-3 into LF at the expected beginning of deviation causes LF to regress and second LF to become dominant. Thus, the dramatic changes in the IGF system in LF compared to other follicles before the beginning of deviation play a crucial role in the events that lead to the beginning of diameter deviation in both cattle and horses. Oestradiol and LH receptors also play a role in cattle. These intrafollicular events prepare the selected follicle for the decreasing availability of FSH and increasing availability of LH. The other follicles of the wave have the same future capability but do not have adequate time to attain a similar preparatory stage.


2004 ◽  
Vol 16 (9) ◽  
pp. 203
Author(s):  
B. C. Sisco ◽  
A. N. Shelling ◽  
P. L. Pfeffer

In monovulatory species such as cattle, one of a cohort of developing follicles assumes dominancy and continues to grow in each follicular wave. After dominant follicle selection, pituitary-derived FSH levels decrease through a negative feedback loop mediated by oestradiol and inhibin A produced by the dominant follicle. The dominant follicle itself only requires very low basal levels of FSH, thus escaping atresia which is the fate of the subordinate follicles. The mechanisms involved in dominant follicle (DF) selection remain unclear. Most studies have focused on the stages following selection. To investigate what roles activin and inhibin play in DF selection we looked at the quantitative changes in the expression of the genes coding for the activin/inhibin subunits (Inhibin α, βA and βB) as well as other genes in the activin pathway (SMAD2, ActRIIA/B, follistatin (FST), FSHR). We examined mRNA levels in follicular granulosa cells (GCs) before (d1.5), during (d2.5) and after (d3.5 and 7) DF selection using real-time RT-PCR. Prior to DF selection, highest levels of inhibin βA, FST and SMAD2 transcripts converged on the largest follicles. Inhibin α, ActRIIA/B and FSHR levels did not correlate with follicular size at this stage. At Day 2.5, highest levels of inhibin βA, inhibin α, FST and SMAD2 transcripts were seen in a single putative DF. ActRIIA/B and FSHR did not show any difference between follicles. By Days 3.5 and 7, a dramatic difference in expression levels of inhibin βA, inhibin α and FST were seen in DF compared to SF. Yet in absolute terms inhibin βA levels decreased after selection, whereas inhibin α levels increased. Inhibin βB expression was only detected in Day 7 GCs and was significantly higher in the DF. These results suggest a shift from an activin environment during the pre and peri-DF selection period, to an inhibin environment following DF selection. Inhibin/activin protein levels in the follicular fluid using western ligand blotting confirmed this. We postulate that the higher activin activity within DF influences the selection mechanism as activin and inhibin have been shown to play a role in gonadotropin regulation in the ovary around the time of selection.


Reproduction ◽  
2020 ◽  
Vol 159 (5) ◽  
pp. 559-569 ◽  
Author(s):  
Victor E Gomez-León ◽  
O J Ginther ◽  
Rafael R Domingues ◽  
José D Guimarães ◽  
Milo C Wiltbank

Previous research demonstrated that acute treatment with GnRH antagonist, Acyline, allowed follicle growth until ~8.5 mm and no dominant follicle was selected. This study evaluated whether deficient LH was the underlying mechanism for Acyline effects by replacing LH action, using human chorionic gonadotropin (hCG), during Acyline treatment. Holstein heifers (n = 24) during first follicular wave were evaluated by ultrasound and randomized into one of three treatments: Control (saline treatments), Acyline (5 µg/kg Acyline), or Acyline+hCG (Acyline plus 50 IU of hCG at start then 100 IU every 12 h). Pulses of LH were present in Control heifers (9 Pulses/10 h) but not during Acyline treatment. Data were normalized to the transition to diameter deviation (day 0; F1 ~7.5 mm). Diameter deviation of the largest (F1) and the second largest (F2) follicle was not observed in Acyline-treated heifers, whereas control heifers had decreased growth of F2 at F1 ~7.5 mm, indicating deviation. Selection of a single dominant follicle was restored by providing LH activity in Acyline+hCG heifers, as evidenced by F1 and F2 deviation, continued growth of F1, and elevated circulating estradiol. Separation of F1 and F2 occurred 12 h (~7.0 mm) earlier in Acyline+hCG heifers than Controls. Circulating FSH was greater in Acyline than Controls, but lower in Acyline+hCG than Controls after day 1.5. In conclusion, dominant follicle selection and growth after follicle deviation is due to LH action as shown by inhibition of this process during ablation of GnRH-stimulated LH pulses with Acyline and restoration of it after replacement of LH action by hCG treatment.


2010 ◽  
Vol 22 (1) ◽  
pp. 171
Author(s):  
M. F. Martínez ◽  
D. Tutt ◽  
L. Proctor ◽  
J. L. Juengel

An experiment was designed to evaluate the effect of different doses of eCG on ovarian follicular dynamics in heifers treated with a Ovsynch plus progesterone protocol. Twenty-five cyclic yearling Black Angus heifers (373.0 ± 35.7 kg), in 2 replicates, received an injection of 100 μg of GnRH (Ovurelin, Bomac Laboratories Ltd., Auckland, New Zealand) i.m. and an intravaginal progesterone device (1.38 g of progesterone; Eazi-Breed CIDR, Pfizer Animal Health, New Zealand) on Day 0 (beginning of the experiment), followed by 500 μg of cloprostenol (PGF, Estrumate, Intervet/Schering-Plough Animal Health, Auckland, New Zealand) i.m. on Day 7, and a second 100 μg of GnRH injection given i.m. on Day 9 (56 h after PGF). At the time of PGF treatment, heifers were randomly assigned to 5 treatment groups to receive 0, 300, 500, 700, or 1000 IU of eCG (Folligon, Intervet/Schering-Plough Animal Health) i.m. Heifers were monitored by ultrasonography (Aloka 900-SSD equipped with a 7.5-MHz linear-array transducer; Aloka, Tokyo, Japan) daily from Day 0 to 9 (GnRH), and then every 12 h until ovulation. Data were analyzed by one-way ANOVA or Kruskall-Wallis test, and means or ranks were compared with LSD or Wilcoxon rank sum tests, respectively. Because a replicate effect was observed (P < 0.05) in the size of the dominant follicle at the second GnRH and prior to ovulation, replicate effect was included in the analysis. The luteal area at PGF treatment was significantly greater (P < 0.01) in heifers that ovulated (750.0 ± 97 mm2) in response to the first GnRH treatment than in those that did not (301.6 ± 42.7 mm2). The diameter of the dominant follicle at the time of PGF treatment was also greater (P < 0.05) in ovulating (11.2 ± 0.4 mm) than in nonovulating (9.7 ± 0.5 mm) heifers. The interval from the first GnRH treatment to the emergence of the next follicular wave was longer (P = 0.50) and more variable in heifers that did not ovulate (2.9 ± 0.4 d; n = 27) than in those that ovulated (1.9 ± 0.2 d; n = 23). There was no effect (P < 0.37) of eCG on the interval from PGF to ovulation (86 ± 1.9 h). The number of ovulations after the second GnRH was higher (P = 0.01) in the group of heifers treated with 1000 IU of eCG (1.8 ± 0.4) than in the other groups (1.0 ± 0.0; 1.1 ± 0.1; 1.2 ± 0.1; 1.0 ± 0.1). There was an effect of day of follicular wave emergence on the number of ovulations (P < 0.01). Heifers with a wave emerging 1 to 3 days after the first GnRH (n = 37), had one ovulation (1.0 ± 0.0), whereas heifers with a wave emerging on Day 4 (3 out of 4 heifers) and Days 5 to 7 (n = 9), ovulated 2 or more follicles. In summary, the multiple ovulation effect occurred when eCG was given to heifers with a follicular wave emerging on or after Day 4, and was potentiated when heifers received 1000 IU of eCG. Although the dose of eCG given at the time of PGF treatment in an Ovsynch program has a significant effect on follicular development, the time of emergence of the dominant follicle appeared to be more important in the ovulation of preovulatory follicle/s after the eCG and the second GnRH treatment.


2002 ◽  
Vol 80 (10) ◽  
pp. 1670-1677 ◽  
Author(s):  
Thomas C.G Bosch ◽  
Konstantin Khalturin

In the last few years more than 100 genes have been identified from Hydra, and well over 80 have been characterized. Since most genes are homologs of genes found in bilaterians, the genetic mechanisms for axial patterning and cell differentiation are evolutionarily conserved. This constitutes something of a paradox. If key developmental-control genes are the same in Hydra and all other organisms, how does one account for the marked differences in development and morphology of the different animal groups? How are taxon-specific features encoded? To examine whether in Hydra, in addition to conserved mechanisms, there are genetic features that control uniquely taxon-specific (Hydra/Hydrozoa/Cnidaria) aspects, we used an experimental strategy that does not require sequence data from related taxa. By means of this unbiased ("knowledge-independent") approach we have identified genes from Hydra encoding signal molecules and effector genes with no sequence similarity to genes in other organisms. When tested functionally, the novel genes were found to be essential for axial patterning and differentiation of Hydra-specific characteristics. Experimental analysis of the cis-regulatory apparatus of these novel genes reveals target sites for novel trans-acting factors. The use of unbiased screening approaches for several other organisms also reveals a large number of novel and taxon-specific genes of as yet unknown function. Thus, comparative data alone may not be sufficient for gaining a full understanding of the development of taxon-specific characteristics.


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