Development Of Follicular Cysts Research Articles

Alterations of Cortisol and Melatonin Production by the Theca Interna Cells of Porcine Cystic Ovarian Follicles.

Simple SummaryThe mechanism of follicular cyst formation is largely unknown but changes in follicular composition are known to be involved. In particular, there is abnormal hormone secretion in cystic follicles. Here, we found there was disruption of hormone secretion in the fluid of cystic follicles in sows. The glucocorticoid receptor was highly expressed, and the melatonin receptor was weakly expressed in cystic follicles compared with control follicles. Thus, secretion of steroid hormones in cystic follicles is disrupted and disturbances in signaling via cortisol and melatonin are involved in the development of follicular cysts in sows.(1) Background: Cortisol and melatonin (MT) act in regulating follicular development. We hypothesized that abnormal levels of cortisol, MT, and steroids in theca interna cells might be involved in the development of follicular cysts in sows. (2) Methods: To test this hypothesis, we measured the mRNA levels of enzymes involved in steroid hormone synthesis, the glucocorticoid receptor (GR), and melatonin receptors (MTRs) in theca interna cells of cystic and normal porcine follicles. (3) Results: The concentrations of estradiol, progesterone, and cortisol were greater in cystic follicles than in control ones (p = 0.034, p = 0.020, p = 0.000), but the concentration of MT was significantly lower (p = 0.045). The levels of GR, 11β-HSD1, and 11β-HSD2 were higher in cystic follicles than in control l follicles. MT types 1 and 2 were significantly lower in cystic follicles (p < 0.05). The mRNA expression levels of genes encoding the steroid hormone synthesis enzymes, steroidogenic acute regulatory protein (StAR), recombinant cytochrome P45011A1 (CYP11A1), and 3β-hydroxysteroid dehydrogenase (3β-HSD) in theca interna cells of cystic follicles were significantly higher than in control follicles. Thus, there was disruption of hormone secretion in the fluid of cystic follicles in sows. (4) Conclusions: The levels of steroid hormones, cortisol and MT are disrupted in porcine cystic follicles.

An Evaluation of the Plasma Levels of Frequently Used Pesticides in Dairy Cattle and Its Possible Correlation with the Occurrence of Follicular Cystic Ovarian Disease: A Case-Control Study

Background: Cystic ovarian disease (COD) is one of the common reproductive disorders which affecting the fertility of dairy cattle induces heavy financial burdens on herds owners. Various insecticides, fungicides and herbicides, collectively known as pesticides are frequently used in the agricultural systems of different countries. Given the fact that pesticides are known to have endocrine disrupting properties, exposure to these compounds may play a role in the development of COD. M aterials and Methods: The plasma concentrations of a complete profile of common pesticides including organophosphorus, organochlorine, and carbamate and pyrethroid compounds in the plasma of cattle with COD compared to healthy controls was examined. Moreover, plasma concentrations of inflammatory cytokines as well as oxidative stress parameters were investigated. R es ults: No significant amounts of any of the pesticides investigated were detectable in the plasma of neither the healthy nor cystic cows. The plasma indices of total antioxidant capacity (TAC), thiol, lipid peroxidation (LPO), and reactive oxygen species (ROS) did not show any significant differences between the affected and the control groups. Tumor necrosis factors alpha (TNF-α), progesterone, lymphocyte, neutrophil, fibrinogen and MCHC had significantly higher amounts in the plasma of COD cows. C onclusion: Findings of the present study do not support the notion that exposure to the studied pesticides is a contributing factor in the development of follicular cysts in dairy cattle. In addition, TNF-α might be affected as a factor in the pathogenesis of COD by an independent pathway of pesticides effect.

Association between liver failure and hepatic UDP-glucuronosyltransferase activity in dairy cows with follicular cysts.

Uridine 5’-diphospho-glucuronosyltransferase (UGT) liver activity was measured using estradiol-17β as a substrate in dairy cows with follicular cysts. The activity was significantly lower than that in dairy cows with normal estrous cycles (P<0.01). Liver disorders, such as fatty liver and hepatitis, were observed in half cows with follicular cysts, and liver UGT activity was lower than that in cows with normal estrus cycles. In addition, the liver UGT activity was significantly lower in dairy cows with follicular cysts without liver disorders than in dairy cows with normal estrous cycles. Therefore, the cows were divided into those with low, middle and high liver UGT activities, and liver disorder complication rates were investigated. The complication rate was significantly higher in the low- (78.1%) than in the middle- (22.2%) and high-level (8.3%) groups, suggesting that liver disorders are closely associated with the development of follicular cysts in dairy cows and that steroid hormone metabolism is delayed because of reduced liver UGT activity, resulting in follicular cyst formation. We conclude that reduced estradiol-17β glucuronidation in the liver and liver disorders are associated with follicular cyst occurrence in dairy cows.

Altered Expression of Pro-inflammatory Cytokines in Ovarian Follicles of Cows with Cystic Ovarian Disease

A growing body of evidence suggests that ovulation shares many of the features of an inflammatory reaction and that cytokines play many diverse and important roles in reproductive biology. The aim of this study was to examine the expression of the pro-inflammatory cytokines interleukin (IL)-1α, IL-6 and tumour necrosis factor (TNF)-α in ovarian cells from cows with cystic ovarian disease (COD) as compared with that in ovarian structures from regularly cycling cows. Expression of genes encoding IL-1α, IL-6 and TNF-α was detected by real-time polymerase chain reaction in follicular cells from ovaries from healthy cows and cows with COD with no significant differences. However, immunohistochemistry showed increased expression of IL-1α, IL-6 and TNF-α in cystic follicles, suggesting that this expression may be related to the persistence of follicular cysts. The effect of COD was evident for IL-1α and TNF-α, and a follicular structure-disease interaction was observed in the expression of all the cytokines evaluated. Thus, altered expression of these proinflammatory cytokines may be related to ovulation failure and development of follicular cysts.

Effect in dedicator of cytokinesis 6 (DOCK6) on steroid production in theca cells of follicular cysts

Ovarian follicular cysts are one of the most common causes of reproductive failure in mammals. A comparative gene expression approach may aid in elucidating the causes of ovarian cyst disease. In the present study, the differential display technique was used to identify mRNA sequences that accumulate preferentially in theca cells of bovine cystic follicles. Dedicator of cytokinesis 6 (Dock6) expression was observed in the theca cells of cystic follicles. Small interfering RNA (siRNA) knockdown of Dock6 increased progesterone (P4) production and StAR expression in theca cells of high-estrogen follicular cysts, but did not affect androstenedione (A4) production. We propose that Dock6 may be a marker associated with the development of follicular cysts. Additionally, Dock6 may be involved in the development of cystic follicles by suppressing P4 production rather than increasing A4 production in theca cells.

Intrafollicular Steroids and Anti-Müllerian Hormone During Normal and Cystic Ovarian Follicular Development in the Cow1

Development of follicular cysts is a frequent ovarian dysfunction in cattle. Functional changes that precede cyst formation are unknown, but a role for anti-Müllerian hormone (AMH) in the development of follicular cysts has been suggested in humans. This study aimed to characterize intrafollicular steroids and AMH during follicular growth in a strain of beef cows exhibiting a high incidence of occurrence of follicular cysts. Normal follicular growth and cyst development were assessed by ovarian ultrasonography scanning during the 8 days before slaughtering. Experimental regression of cysts was followed by rapid growth of follicles that reached the size of cysts within 3-5 days. These young cysts exhibited higher intrafollicular concentrations of testosterone, estradiol-17beta, and progesterone than large early dominant follicles did in normal ovaries, but they exhibited similar concentrations of AMH. Later-stage cysts were characterized by hypertrophy of theca interna cells, high intrafollicular progesterone concentration, and high steroidogenic acute regulatory protein mRNA expression in granulosa cells. Progesterone and AMH concentrations in the largest follicles (> or =10 mm) and cysts were negatively correlated (r = -0.45, P < 0.01). Smaller follicles (<10 mm) exhibited higher intrafollicular testosterone and estradiol-17beta concentrations in ovaries with cysts compared to normal ovaries. During follicular growth, AMH concentration dropped in follicles larger than 5 mm in diameter and in a similar way in ovaries with and without cysts. In conclusion, enhanced growth and steroidogenesis in antral follicles <10 mm preceded cyst formation in cow ovaries. Intrafollicular AMH was not a marker of cystic development in the cow, but low AMH concentrations in cysts were associated with luteinization.

Exposure of adult rats to estradiol valerate induces ovarian cyst with early senescence of follicles

Environmental and therapeutic estrogens are known to play an important role in modulating the reproductive life and pubertal maturation in males as well as in females. Animal studies have shown that exogenously administered estrogen induces follicular cysts. However, the probable mechanisms underlying this abnormal ovarian development and its impact on steroidogenesis have been ill defined. The present study was therefore carried out to understand the ontogeny of ovarian pathology owing to adult estrogenisation. Regularly cycling female Holtzman rats were sacrificed at one week, two weeks, three weeks and four weeks after a subcutaneous administration of 2 mg of estradiol valerate (E 2V). The effect of this supra-physiological estrogen on serum endocrine profiles, development of follicular cysts, follicular apoptosis and expression of markers of folliculogenesis viz., estrogen receptor (ER)-β, inhibin A and progesterone receptor (PR) were studied. Results indicate a temporal augmentation of steroidogenesis, which was associated with induction of follicular cyst with theca cell hyperplasia and induction of apoptosis in the primary and secondary follicles of the ovaries. Immuno-histochemical localization showed an increase in inhibin A with a reduction in ER-β and PR indicating early maturation, poor follicle growth and granulosa cell differentiation. Results indicate that exposure to exogenous estrogen in adulthood can have deleterious effects on the ovarian physiology and endocrinology which may ultimately lead to cystogenesis, loss of follicle pool and early senescence.

Supra-basal progesterone concentrations during the follicular phase are associated with development of cystic follicles in dairy cows

The objective of this study was to test the hypothesis that supra-basal concentrations of progesterone during the follicular phase are associated with the development of follicular cysts. Twenty-five non-lactating dairy cows were used in the study, which was performed over five identical replicate trials. Luteolysis was induced during the mid-luteal phase. Transrectal ultrasonography was performed daily to determine the occurrence/timing of ovulation. Plasma samples were collected for progesterone, oestradiol and luteinizing hormone (LH) analysis. Three cows failed to ovulate (cystic anovulatory) but did ovulate in a subsequent replicate (cystic ovulatory). Eight cows from the appropriate replicates were used as control cows (normal group). Follicular growth patterns and plasma oestradiol concentrations were similar between the three groups. However, the plasma progesterone concentrations during the follicular phase were twofold higher in the cystic anovulatory group ( P < 0.01). Furthermore, no LH surge was detected in these animals. While LH pulse amplitude was similar between groups, LH pulse frequency in the cystic anovulatory group was attenuated ( P < 0.05). In conclusion, the formation of follicular cysts were preceded by elevated plasma progesterone concentrations and the suppression of the LH surge.

Information on Regulation of Reproductive Cyclicity in Cattle

Reproductive cycles are regulated by hormones. The purpose of this paper is to give an overview of recent information on hormonal regulation of reproductive cycles in order to allow increased understanding of programs that are currently being developed or will be developed for improving reproductive efficiency in cattle.&#x0D; Figure 1 shows a typical hormonal profile for 4 key reproductive hormones during the estrous cycle of the cow. Progesterone comes from the corpus luteum and increases after the time of ovulation and then decreases at the time of luteolysis. Prostaglandin (PG) F2a comes from the nonpregnant uterus and is the hormone responsible for luteolysis. AI, shown below PGF2a is secreted in distinct pulses near the time ofluteolysis. Estradiol-17B increases early in the cycle and after the time of luteolysis. This increase in estradiol causes estrus behaviour and the LH surge. The LH surge is responsible for ovulation of the preovulatory follicle. Ovulation occurs about 28 h after the initiation of the LH surge.&#x0D; The remainder of this manuscript will provide more depth on this simplified view of the estrous cycle by summarizing some recent information on: regulation of follicular development, regulation of corpus luteum function, and how this information can be applied to understanding mechanisms involved postpartum anestrus and development of follicular cysts.

Modulation of Murine Hair Follicle Function by Alterations in Ornithine Decarboxylase Activity

Mice that overexpress a mutated ornithine decarboxylase (ODC) transgene in outer root sheath keratinocytes of the hair follicle were used to study the role of this enzyme in regulating hair follicle structure and function. These transgenic mice have a normal first hair cycle, but lose their hair completely beginning 2-3 wk after birth. Transgene overexpression in follicular keratinocytes is first detected at day 12 after birth, coincident with the development of follicular cysts in the upper portion of the dermis. The onset of keratin 6 expression also begins around day 12; because the promoter/regulatory region of the bovine keratin 6 gene was used to target ODC transgene expression of hair follicle keratinocytes, these data demonstrate the faithful temporal and cell type-specific expression of the K6 -driven transgene. The ODC inhibitor 2-difluoromethylornithine could prevent hair loss and partially normalize skin histology if administered before the onset of ODC overexpression. 2-Difluoromethylornithine could also reactivate hair growth in animals with complete hair loss. Our results suggest that ODC is an important regulatory gene for the mouse hair follicle.

Induction of ovarian cysts in progesterone-synchronized immature rats: evidence that suppression of follicular aromatase activity is not a prerequisite for the induction of cystic follicles.

Serum hormone profiles for women and animals with cystic ovaries have led to the hypothesis that elevated serum LH and androgens are involved in the induction of ovarian follicular cysts. To test the ability of LH-like activity to induce cysts, immature rats (bearing progesterone implants to suppress endogenous LH secretion) were assigned to treatment groups that received 0 (control), 0.1, 0.5, or 1.5 IU hCG twice daily for 9 days beginning on day 27 of life. Serum progesterone concentrations were maintained at approximately 156 ng/ml throughout the in vivo treatment period. By the morning of day 36 (day 10 of treatment) the largest follicles in ovaries from control animals were at the small antral stage of development. In contrast, the largest follicles in ovaries from rats receiving 0.1, 0.5, and 1.5 IU hCG were primarily at the large antral, precystic, and cystic stages of development, respectively. On all days tested, progesterone, androstenedione, and estradiol accumulation in medium alone was greater for follicles from rats receiving hCG than for follicles from control rats. Progesterone and androstenedione increased in response to cAMP in vitro in follicular incubations from both control and hCG-treated animals. Only estradiol production by follicles from rats treated with 0.1 or 0.5 IU hCG increased in response to cAMP in vitro. Follicles from all treatment groups produced significantly more estradiol in the presence of a saturating amount of aromatizable substrate than in medium alone. Indeed, on day 36, cystic follicles produced more than 8 ng estradiol when incubated in the presence of either androstenedione or testosterone. In addition, more androstenedione was accumulated in vitro when developing cysts were incubated with exogenous testosterone than when noncystic follicles were incubated under similar conditions. The results of these experiments demonstrate that chronic stimulation by LH-like activity is capable of inducing follicular cysts in a time- and dose-related manner in intact noncycling immature rats. The ability of these cysts to produce 1-2 ng estradiol in medium alone and even greater amounts of estradiol in the presence of exogenous androgen indicates that inhibition of the ability of FSH to induce and stimulate follicular aromatase activity is not a prerequisite for the induction of follicular cysts in these animals. Finally, the increasing ability to accumulate androstenedione in the presence of exogenous testosterone suggests that follicular 17 beta-hydroxysteroid oxidoreductase activity increases in response to chronic stimulation by low doses of LH-like activity during the development of follicular cysts.

Luteinization of follicle cysts in rat ovaries as an effect of potassium iodine administration

Following X-irradiation or subtotal castration rats developed follicular cysts of the ovaries; this was accompanied by hyperestrogenism of the organism manifested in the appearance of a constant estrus. In connection with the fact that the development of follicular cysts was caused by insufficiency of the luteinizing function of the hypophysis an attempt was made to stimulate the luteinizing hormone production by microdoses of potassium iodine. The daily administration of KI in a dose of 500 γ provoked within 2 weeks luteinization of follicular cysts and their transformation into corpus luteum. Luteinization of the cysts was accompanied by a marked reduction of the body estrogen level, as manifested by the arrest of estrus with subsequent normalization of the estral cycle or a prolonged diestrus.