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At least 19 recordsLinked to original sources

PubMed2001

Combined effect of follicle-follicle interactions and declining follicle-stimulating hormone on murine follicle health in vitro.

Follicle selection occurs throughout an adult female's reproductive life, with selected, dominant follicle(s) developing to the preovulatory stage whereas the remaining, subordinate follicles within the growing cohort instead undergo atresia and die. To date, most research into follicle dominance has concentrated on its endocrine regulation, although it seems likely that intraovarian mechanisms are also involved in its regulation. We demonstrate here that the response of singly cultured murine follicles to declining concentrations of FSH depends on their developmental stage, with follicles at an earlier stage of development being much more susceptible than mature follicles to a lowering of FSH levels. We then extrapolate this information to follicle cocultures, in which a large dominant follicle was grown with a small subordinate follicle in a manner that maintained a dominant/subordinate relationship, with follicle health assessed by a terminal transferase-mediated 2'-deoxyuracil 5'-triphosphate nick end-labeled reaction on whole-follicle mounts. Our investigations show a combined negative effect of coculture and FSH withdrawal on small subordinate follicles, such that subordinate follicles cocultured with dominant follicles and subjected to a lowering of FSH levels during the culture period exhibit a greatly increased incidence of apoptosis in the granulosa cells (750% increase) compared with that exhibited by the dominant follicles (97% increase). We suggest that a similar interaction between endocrine and intraovarian factors regulates follicular dominance in vivo, such that dominant follicles, in addition to bringing about a fall in FSH levels via the hypothalamic-pituitary axis, exert local, direct effects on subordinate follicles, with both of these influences combining to induce atresia in subordinate follicles.

Animals↗

PubMed2000

Selection of the dominant follicle in cattle: role of two-way functional coupling between follicle-stimulating hormone and the follicles.

The functional coupling between the declining portion of the FSH surge and the growing follicles of a wave was studied by treating heifers with a minimal dose of estradiol to decrease FSH concentrations without an associated change in LH concentrations. Estradiol treatment when the largest follicle reached >/= 6.0 mm (Hour 0) resulted in depression of both FSH concentrations and diameter of the largest follicle by Hour 8. The smaller follicles were also inhibited. These results supported the hypothesis that FSH continues to be needed by the growing follicles even when the FSH concentrations are decreasing during the declining portion of the FSH surge. Estradiol treatment when the largest follicle was >/= 8.5 mm (expected time of follicular deviation) also resulted in a transient decrease in both FSH concentrations and diameter of the largest follicle, but the diameters of the smaller follicles were not affected. These results supported the hypothesis that the low concentrations of FSH at the expected time of deviation, although inadequate for the smaller follicles, were required for continued growth of the largest follicle. In another study, ablation (Hour 0) of the largest follicle was done at >/= 7.5 mm vs. >/= 8.5 mm. The mean FSH concentrations for the 8.5-mm groups were greater for the ablation group than for the control group at Hours 8 and 12, but there was no difference between the 7.5-mm groups at any hour. These results supported the hypothesis that by the time the largest follicle reaches the expected beginning of deviation it has developed a greater capacity for suppressing FSH. It is postulated that the essence of the selection of a dominant follicle is a close two-way functional coupling between changing FSH concentrations and follicular growth.

Animals↗

PubMed2001

Effects of the persistent dominant follicle on the ability of follicle stimulating hormone to induce follicle development and ovulatory responses.

Three experiments were conducted to evaluate the effect of an induced first wave persistent dominant follicle on folliculogenesis and ovulatory responses induced by FSH. On d 6 of a synchronized estrous cycle (d 0 = estrus), cows were treated with a Syncromate-B implant and two injections of PGF2, (25 mg, 0700 h; 15 mg, 1900 h, i.m.). Cows in the control group retained a first-wave persistent dominant follicle, but in the aspirated group, the first-wave dominant follicle was removed via transvaginal aspiration on d 10 (d 0 = estrus). Beginning on d 12, cows received 32 mg of FSH-P i.m. in decreasing doses at 12-h intervals over a 4-d period. On d 15, the Syncromate-B implant was removed, and cows were ovariectomized (experiment 1, n = 8) or inseminated (experiment 2, n = 11) at 10 and 22 h after the onset of estrus. Cows in experiment 3 received a used controlled intravaginal drug releasing (CIDR) device and two injections of PGF2alpha (25 mg, 0700 h; 15 mg, 1900 h; i.m.) on d 6. On d 8, the first-wave dominant follicle was aspirated (n = 6) or left intact (n = 5), and FSH treatment was initiated (20 mg of Folltropin in decreasing doses at 12-h intervals over a 4-d period), and on d 10 the used CIDR device was removed from all cows. Ovarian follicle size and number were examined daily by ultrasonography from d 5 of the estrous cycle. The persistent dominant follicle increased in size from 10.7 mm on d 5 to 15.4 mm on d 10 (experiments 1 and 2), and from 9 mm on d 5 to 20.4 mm on d 11 (experiment 3). From d 11 to 14, the number of class 1 (2 to 5 mm) follicles was lower in the aspirated group than in the control group; the number of class 2 (6 to 9 mm) follicles was higher on d 12 and 13 for the aspirated group (experiments 1 and 2). The number of class 3 (> or =10 mm) follicles was higher in the aspirated group on d 14 to 16, but the same on d 17. Ovarian and embryo responses to superovulation did not differ between groups. In experiment 3, the numbers of class 1, 2, and 3 follicles, as well as ovarian and embryo responses following ovulation did not differ between groups. Initiation of exogenous FSH treatment appears to override any systemic inhibitory effect that a persistent dominant follicle may be exerting at the pituitary and possibly the ovary.

Animals↗

PubMed1987

Influence of stage of cycle, corpus luteum location, follicle size, and number of large follicles on estradiol-17 beta concentrations in bovine follicles.

Concentrations of estradiol-17 beta in follicular fluid were correlated to follicular size, stage of estrous cycle, location of corpus luteum, and presence of large follicles. Paired ovaries were obtained from 481 nonpregnant cows at slaughter and follicles were classified as ipsilateral or contralateral to the corpus luteum. Follicular fluid estradiol-17 beta concentrations from 2494 small, 1485 medium, and 396 large follicles were quantified by radioimmunoassay. Stage of estrous cycle was estimated by visual examination of the corpus luteum. Follicles in stage 1 of the estrous cycle (d 1 to 4) had the highest estradiol-17 beta concentration and the smallest mean follicular diameter. Location of follicles relative to the corpus luteum had no influence on estradiol-17 beta concentrations. As follicular size increased, concentration of estradiol-17 beta also increased. The presence of a single large follicle did not affect the concentration of estradiol-17 beta in medium or small follicles. In contrast, if multiple large follicles occurred in the same cow, concentrations of estradiol-17 beta were significantly lower in medium but not small follicles.

Animals↗

PubMed1977

[The mechanism of follicle growth. II. The mode of action of the follicle-stimulating hormone (FSH) on follicle growth (author's transl)].

The mode of action of the follicle-stimulating hormone (FSH) on ovarian follicle growth was studied in hypophysectomized rats using the histologic, autoradiographic and histochemical techniques. The follicle growth was stimulated by the administration of both FSH and estrogen. The histologic finding of the follicle growth induced by the two hormones was different. Namely, after the administration of FSH, the theca layer was thick, but after the administration of estrogen, it was thin. 3H-thymidine and 3H-leucine were used to investigate cell division in a growing follicle. The uptake of 3H-thymidine and 3H-leucine by the theca layer was enhanced remarkably by FSH. On the other hand, the uptake of 3H-thymidine by the granulosa layer was enhanced by FSH or estrogen, while the grain count of granulosa cells was increased only by the administration of estrogen. Moreover, the administration of FSH resulted in an increase of the enzyme activity of glucose-6-phosphate dehydrogenase (G-6-PD), DELTA5-3beta-hydroxysteroid dehydrogenase (3beta-HSD) and alkaline phosphatase (ALPase) in the theca layer. Furthermore, the administration of FSH caused an increase in the serum estradiol and estriol of rats, whereas the administration of estrogen did not. It seems possible, therefore, that FSH stimulated proliferation of theca cells and produced estrogen. The results suggest that the estrogen produced by the theca cells might stimulate proliferation of granulosa cells; consequently, follicle growth might be induced.

Animals↗

PubMed1984

[Recent findings on follicle and oocyte maturation. 1. Development of follicles and maturation of follicles].

A review is given of the present knowledge of the development of follicles and oocytes, especially in the human. The first report deals with the course of development of follicles from the beginning in the fetal ovary to the mature Graafian follicle in the adult women. Questions of terminology, functional morphology and important aspects of the regulation of follicular growth are discussed. The last part of the paper summarizes the present day possibilities in monitoring growth and maturation of ovarian follicles in clinical practice.

Androstenedione↗

PubMed2003

Regulation of ovarian primordial follicle assembly and development by estrogen and progesterone: endocrine model of follicle assembly.

The assembly of the developmentally arrested primordial follicle and the subsequent transition of the primordial follicle to the primary follicle are critical processes in normal ovarian physiology that remain to be elucidated. Ovarian follicles do not proliferate and the primordial follicles present in the neonate represent the total number of gametes available to a female throughout her reproductive life. The primordial follicles are oocytes surrounded by less differentiated squamous granulosa cells and are derived from oocyte nests, and primary follicles are oocytes surrounded by a single layer of cuboidal granulosa cells that have initiated follicle development. Abnormalities in primordial follicle assembly, arrest, and development (i.e. primordial to primary follicle transition) can cause pathological conditions such as premature ovarian failure. In this study newborn rat ovaries were cultured for 7 d. The rate of primordial follicle assembly in vivo was identical with the rate in vitro. Interestingly, the rate of primordial follicle transition to the primary follicle was found to be 3 times greater in culture. This abnormal rate of primary follicle development in culture suggests the primordial follicle does not arrest in development as observed in vivo. To investigate this phenomena newborn rat ovaries were cultured in the presence of progesterone, estradiol or calf serum. Estradiol, progesterone, or calf serum significantly reduced the level of initial primordial to primary follicle transition. Approximately 60% of follicles make the primordial to primary follicle transition in control ovaries and about 30% in treated ovaries. Steroids and calf serum had no effect on the primordial to primary follicle transition in ovaries collected and cultured from postnatal 4-d-old rats, suggesting the effects observed are restricted to the initial wave of primordial to primary follicle transition. Interestingly, progesterone was also found to significantly reduce the rate of primordial follicle assembly. All viable oocytes assembled into primordial follicles in control ovaries and approximately 40% remained unassembled in progesterone-treated ovaries. Progesterone was also found to reduce primordial follicle assembly in vivo with 10% of the total follicles remaining unassembled in progesterone injected neonatal animals. Analysis of cellular apoptosis demonstrated that progesterone inhibited the coordinated oocyte apoptosis required for primordial follicle assembly. The hypothesis developed is that high levels of maternal and fetal steroids prevent premature primordial follicle assembly and primordial to primary follicle transition in the embryo. After birth steroid levels fall dramatically and the primordial follicles are free to assemble and initiate development. These observations suggest a novel role for steroids and the maternal-fetal endocrine unit in the control of ovarian primordial follicle assembly and early follicular development.

Animals↗

PubMed1997

Preantral ovarian follicles in serum-free culture: suppression of apoptosis after activation of the cyclic guanosine 3',5'-monophosphate pathway and stimulation of growth and differentiation by follicle-stimulating hormone.

Progression of preantral follicle development is essential to further follicle maturation and ovulation, but there are few models for studying the regulation of preantral follicle survival and growth. We have evaluated preantral follicle survival in vivo and in vitro, and have developed a serum-free rat follicle culture system that can be used to characterize the regulation of preantral follicle growth and differentiation. Analysis of ovarian cell DNA fragmentation during the first wave of follicle growth in the infantile rat indicated negligible apoptosis up to day 16 of age. However, a major increase in apoptosis was found by day 18, a time point associated with the appearance of large antral follicles. In situ analysis confirmed that apoptotic DNA fragments were limited to antral follicles. Culture of individual preantral follicles mechanically dissected from ovaries of 12- or 14-day-old rats in serum-free conditions led to major increases in follicle cell apoptosis, similar to that seen in cultures of antral and preovulatory follicles. In contrast to antral and preovulatory follicles, treatment of preantral follicles with gonadotropins or cAMP analogs did not prevent apoptosis. However, treatment with 8-bromo-cGMP or 10% serum suppressed apoptosis by 75% in cultured preantral follicles. In situ analysis identified granulosa cells as the cell type susceptible to apoptosis regulation. Taking advantage of the ability of the cGMP analog to suppress apoptosis, we evaluated the potential of FSH as a growth factor. In the absence of serum, FSH treatment for 48 h did not affect follicle size compared to controls; however, treatment with the cGMP analog together with FSH increased follicle diameter (13%; P < 0.01) and viable cells (2.4-fold; P < 0.01) compared to control values. Immunoblot analysis further indicated that the inhibin-alpha content of the cultured follicles was increased by treatment with the combination of FSH and 8-bromo-cGMP, demonstrating the induction of follicle cell differentiation during culture. Therefore, we demonstrated that activation of the cGMP pathway promotes the survival of cultured preantral follicles and that in the presence of alpha cGMP analog, FSH is a growth and differentiation factor for preantral follicles. The present serum-free follicle culture model system will be useful in further evaluation of the regulation of growth and differentiation of preantral follicles.

Aging↗

PubMed2002

Effects of ovarian follicle ablation on FSH, oestradiol and inhibin A concentrations and growth of other follicles in sheep.

The aim of this study was to examine the effect of removal of the largest follicle or all visible follicles during the first follicle wave on subsequent follicular growth, steroid, inhibin A and gonadotrophin secretion in sheep. On day 4.5 of a synchronized oestrous cycle, ewes (n = 18) were assigned to one of three groups which underwent either no treatment (control), ablation of the largest follicle (largest follicle aspirated and cauterized via laparotomy) or ablation of all follicles (all visible follicles ablated). Between day 0 and day 10 of the oestrous cycle, blood samples were collected every 8 h and ovaries were examined daily using transrectal ultrasonography. The lifespan of the second largest follicle (number of days > 3 mm in diameter) was longer (6.7 +/- 0.9 days; P < 0.05) and the maximum diameter tended to be greater (4.8 +/- 0.3 mm; P = 0.07) in ewes in which the largest follicle was ablated than in the control ewes (3.8 +/- 0.4 days; 4.2 +/- 0.3 mm). There was no difference in the day of emergence of the second follicular wave between groups (day 6.9 +/- 0.4). However, the peak of the transient increase in FSH concentrations after ablation was earlier (day 5.67 +/- 0.15; P < 0.05) in ewes in which all follicles were ablated than in control ewes (day 6.72 +/- 0.36); the timing in ewes that had only the largest follicle ablated was intermediate (day 6.11 +/- 0.28). Serum inhibin A concentrations were about three-fold lower (P < 0.05) in both follicle ablation groups than in the control group. The numbers of follicles 2-3 mm in diameter during the first 3 days of the second follicular wave were greater in 'ablated ewes' (both groups had 2.6 +/- 0.2 follicles day-1) than in control ewes (1.7 +/- 0.3 follicles day-1). It is concluded that: (i) transient increases in FSH concentrations precede the emergence of follicle waves; (ii) ablation of all follicles on day 4.5 after oestrus advanced the timing of the next peak in FSH concentrations and the numbers of small follicles associated with the development of the second follicular wave; and (iii) ablation of the largest follicle resulted in an increase in the lifespan of the second largest follicle, indicating a regulatory role of large dominant follicles over smaller subordinate follicles.

Analysis of Variance↗

PubMed1997

Role of diameter differences among follicles in selection of a future dominant follicle in mares.

Follicles > or = 5 mm were ablated in pony mares by a transvaginal ultrasound-guided technique on Day 10 (ovulation = Day 0). Follicle emergence (at 15 mm, experiment 1; at 6 mm, experiment 2) and development of the new wave was monitored by transrectal ultrasound. Deviation was defined as the beginning of a marked difference in growth rates between the two largest follicles. In experiment 1, mares were grouped (n = 4 per group) into controls, ablation-controls (ablations at Day 10 only), and a two-follicle model (periodic ablation sessions so that only the two largest follicles developed). There were no significant indications that the two-follicle model altered follicle diameters, growth rates, or time intervals of the two retained follicles at or between events (follicle emergence, deviation, and ovulation). In experiment 2, the two-follicle model (n = 14) was used for follicle and hormonal characterization and hypothesis testing, without the tedious and error-prone necessity for tracking many (e.g., 20) individual follicles. The future dominant follicle emerged a mean of 1 day earlier (p < 0.008) than the future subordinate follicle, the growth rates for the two follicles between emergence and deviation (6 days later) did not differ, and the dominant follicle was larger at the beginning of deviation (23.1 +/- 0.8 mm versus 19.6 +/- 0.9 mm; p < 0.0001). Mean FSH and LH concentrations increased (p < 0.05) concomitantly from emergence of the future dominant follicle and peaked 3 days later when the follicle was a mean of 13 mm. Thereafter, the two hormones disassociated until ovulation: FSH decreased and LH increased. Results supported the hypothesis that the future dominant follicle has an early size advantage over future subordinate follicles and indicated that the advantage was present as early as 6 days before deviation.

Animals↗

PubMed1996

Hormonal regulation of apoptosis in early antral follicles: follicle-stimulating hormone as a major survival factor.

Hormonal regulation of apoptosis has been studied in cultured preovulatory follicles. Because early antral follicles are most vulnerable to undergo atretic degeneration under physiological conditions in vivo, the present studies were designed to investigate the hormonal regulation of apoptosis using in vitro culture of early antral follicles. Rats were implanted with diethylstilbestrol at 24 days of age to stimulate the development of early antral follicles, and ovaries were collected at day 27 of age. Early antral follicles were dissected and cultured (four per vial) for 24 h with or without hormonal treatments. After culture, DNA was extracted from follicles, and the degree of apoptotic DNA fragmentation was determined using 3'-end labeling and gel electrophoresis. In situ analysis of apoptotic DNA fragmentation revealed that granulosa cells in these follicles are the main cell type undergoing apoptosis. Follicles cultured in the absence of hormones showed a 12-fold increase in the level of apoptotic DNA fragmentation which was prevented by treatment with FSH in a dose-dependent manner (60% maximal suppression and apparent ED50 of 30 ng/ml). Similarly, treatment with (Bu)2cAMP also suppressed follicle apoptosis. Treatment with LH or human CG, however, minimally suppressed apoptotic DNA fragmentation (35% maximal suppression). Insulin-like growth factor-I (IGF-I) also suppressed apoptosis by 45%. Moreover, the suppressive effect of FSH on apoptosis was partially reversed by coincubation with IGF-binding protein-3, suggesting a potential mediatory role of endogenous IGF-I. However, recombinant bovine GH had no effect on follicle apoptosis despite its ability to stimulate IGF-I messenger RNA (mRNA) levels. Incubation of follicles with epidermal growth factor (EGF) and basic fibroblast growth factor maximally suppressed follicle apoptosis by only 32% and 42%, respectively. Ligand binding analysis indicated the minimal effectiveness of EGF on apoptosis in early antral follicles, as compared with its potent action in preovulatory follicles reported earlier, may be due to a 3.5 fold increase in EGF receptor concentration in the mature follicles. High doses (150 or 500 ng/ml) of interleukin-1beta also suppressed apoptosis by 48% whereas treatment with an NO generator, sodium nitroprusside, or a cyclic GMP analog suppressed apoptosis as effectively as that of FSH. Furthermore, treatment with activin resulted in a dose-related suppression of follicle apoptosis, reaching a maximal 40% suppression. In contrast, cotreatment of activin with its binding protein, follistatin, abolished this effect. Collectively, these data demonstrated a stage-dependent difference in the hormonal regulation of follicle apoptosis. Although FSH, LH/human CG, GH, IGF-I, EGF, basic fibroblast growth factor, and interleukin-1beta are all effective survival factors for preovulatory follicles, FSH is a major survival factor for early antral follicles, the stage during which a majority of follicle undergo atresia under physiological conditions.

Activins↗

PubMed1999

Selection of the dominant follicle in cattle: establishment of follicle deviation in less than 8 hours through depression of FSH concentrations.

Deviation in follicle diameter in cattle is characterized by continued growth of the largest follicle of a follicular wave and a reduction or cessation of growth of the smaller follicles. Deviation begins when the largest follicle reaches about 8.5 mm. Two experiments were done to test the hypothesis that the deviation mechanism is established in < 8 h, as indicated by the temporal relationships between follicle removal and an increase in FSH concentrations (Experiment 1) and between a decrease in FSH concentrations and follicle inhibition (Experiment 2). In Experiment 1, the role of the first follicle to reach 8.5 mm was studied by follicle ablation (Hour 0). The combined mean FSH concentrations for the control group (n = 8) and ablation group before ablation (n = 7) progressively decreased (P < 0.02) over two 8-h intervals before the largest follicle reached > or = 8.5 mm (Hour-16, 1.77 +/- 0.11 ng/mL; Hour 0, 1.49 +/- 0.08 ng/mL). In controls, the concentrations continued to decrease (P < 0.02) until Hour 10 (1.21 +/- 0.09 ng/mL). Ablation of the largest follicle at > or = 8.5 mm resulted in increased (P < 0.02) circulating FSH concentrations between Hours 5 (1.34 +/- 0.04 ng/mL) and 8 (1.61 +/- 0.09 ng/mL). Growth rate of the second-largest follicle between Hours 0 and 8 was greater (P < 0.05) in the ablation group than in the controls, and the second largest follicle became dominant in 7 of 7 heifers following ablation of the largest follicle. In Experiment 2, a minimal single injection of a depressant of FSH concentrations (4.4 mL of steroid-reduced follicular fluid) was given when the largest follicle was a mean of 8.4 mm (Hour 0; controls, n = 4; treated, n = 4). An interaction of group and hour (P < 0.005) for FSH concentrations was attributable to an FSH decrease (P < 0.002) by Hour 6 and an increase (P < 0.002) between Hours 9 and 12 in the treated group. The growth rate of the largest follicle between Hours 0 and 12 was less (P < 0.05) in the treated group (0.2 +/- 0.2 mm/12 h) than in the control group (1.2 +/- 0.4 mm/12 h). The reduced diameter was recorded within 6 h after suppression of FSH concentrations, supporting the hypothesis. Our preferred interpretation is that when the largest follicle reaches a critical diameter of about > or = 8.5 mm, FSH concentrations continue to decrease and become lower than required by the smaller follicles but not the largest follicle. The results further indicate that a close temporal coupling between a change in FSH concentrations and the follicular response could establish the deviation mechanism in < 8 h or before the second largest follicle reaches a similar critical diameter.

Animals↗

PubMed1993

Regulation of hair follicle development: an in vitro model for hair follicle invasion of dermis and associated connective tissue remodeling.

During embryonic development presumptive hair follicle cells of epithelial and mesenchymal origin are determined in defined body locations. This is followed by rapid proliferation of epithelial cells and associated penetration into the dermis in response to as yet undetermined signals. A collagen matrix culture system, which maintains the three-dimensional relationships of hair follicle cells to each other, was developed to study the regulation of the enlargement of immature hair follicles and the accompanying remodeling of the dermis. In studies with a heterogeneous dermis-derived preparation of murine hair follicles, ranging in size from the earliest down-growing budding cell mass to hair-forming follicles, we had previously shown that cell proliferation was stimulated by cholera toxin and epidermal growth factor, but only the epidermal growth factor-stimulated proliferation was accompanied by digestion of the collagen matrix due to release of collagenolytic enzymes. Further studies revealed that transforming growth factor-alpha also stimulated hair follicle cell proliferation and collagenase release. However, although transforming growth factor-beta inhibited the transforming growth factor-alpha-stimulated proliferation, it enhanced the release and activation of collagenases and other gelatin-degrading enzymes detectable by gelatin zymography. Stimulation of collagenolytic activity depended on the three-dimensional hair follicle structure and did not occur in monolayer cultures of hair follicle cells. Comparison of hair follicle buds with more developed dermis-derived hair follicles, plated at the same cell density (based on DNA content), suggested that a greater fraction of cells in the bud-stage follicle responded to the growth factors by release of collagenases. Possibly only the cells in the advancing portion of growing hair follicles that are closest to the dermal papilla cell cluster produce the collagenases in response to growth factors. To examine the participation of dermal papilla cells in collagenase release and activation, several immortalized rat whisker dermal papilla cell lines were co-cultured with mouse hair follicle buds. Co-culture resulted in a marked enlargement of follicles as well as activation of the 92-kDa type IV collagenase, produced by hair follicle buds, that correlated with ability of the dermal papilla cells to stimulate hair formation in grafts of hair follicle buds on nude mice. Dermal papilla cells cultured alone produced the 72-kDa type IV collagenase, which was also activated during co-culture with hair follicle buds. Thus, two activities, both relevant for hair follicle development, namely, cell proliferation and release and activation of collagenases, have been stimulated in immature hair follicle buds by either growth-factor supplementation or interaction with dermal papilla cells.(ABSTRACT TRUNCATED AT 400 WORDS)

3T3 Cells↗

PubMed2001

Changes in follicle-stimulating hormone and follicle populations during the ovarian cycle of the common marmoset.

The common marmoset (Callithrix jacchus) belongs to the family Callitrichidae, the only anthropoid primates with a high and variable number of ovulations (one to four). An understanding of folliculogenesis in this species may provide some insight into factors regulating multiple follicular growth in primates. The aims of this study were to characterize in detail changes in the antral follicle population at different stages of the ovarian cycle, to characterize the marmoset FSH profile, and to relate cyclic changes in FSH to changes in follicle sizes and circulating estradiol concentrations. Fifty-five pairs of ovaries were collected (32 of which were at five distinct stages of the cycle) from adult marmosets, and antral follicles were manually excised and separated into four size groups. Daily urinary FSH and plasma estradiol and progesterone concentrations from Day 0 of the follicular phase to 2 days postovulation were measured in 22 marmosets using enzyme immunoassays. The FSH profile revealed two distinct peaks, on Days 2 and 6, during the 10-day follicular phase, with a marginal periovulatory increase on Days 9 and 10. Estradiol levels rose significantly (P: < 0.05) above baseline (Days 1-4) on Day 5 and continuously increased to a peak on the day preceding ovulation (Days 8 and 9). Follicle dissection revealed a high (mean = 68) and variable (range, 14-158) total number of antral follicles >0.6 mm. The number of antral follicles significantly declined (P: < 0.001) with age. The number of preovulatory follicles (>2 mm) was positively correlated with the number of antral follicles (P: < 0. 001) and tended to be negatively related to age (P: = 0.06). The number of antral follicles did not vary significantly with stage of the ovarian cycle, although the follicle size distribution was cycle-stage dependent (P: < 0.05). Follicles >1.0 mm appeared only in the follicular phase, and preovulatory follicles (>2.0 mm) appeared only at the end of the follicular phase (Days 7-9). The Day 2 FSH peak corresponded to emergence of a population of medium-size antral follicles, and the Day 6 peak was consistent with rising estradiol levels and appearance of the preovulatory follicles. These results suggest that some aspects of marmoset folliculogenesis are comparable to those in Old World primates, including the absence of multiple follicular waves and the appearance of an identifiable dominant follicle in the midfollicular phase. However, the midphase FSH peak, multiple dominant follicles, and abundance of nonovulatory antral follicles differ strongly from the pattern in Old World primates and humans. The findings are discussed in relation to the regulation of growth of multiple ovulatory follicles and provide the basis for further studies on factors influencing the dynamics of follicular growth and development in this species.

Animals↗

PubMed1999

Activin from secondary follicles causes small preantral follicles to remain dormant at the resting stage.

The purpose of the present study was to investigate 1) whether activin A can cause primary follicles to become dormant at the resting stage, and 2) the role of the secondary follicle on follicular growth of primary follicles. Preantral follicles (100-120 microm in diameter) harvested from adult mice and cultured in in vitro follicle culture system showed a significant increase in size and estrogen and inhibin secretion in response to FSH, but the administration of activin A blocked the effect of FSH. Withdrawal of activin A not only restored the follicular response to FSH but also enhanced the effect of FSH, indicating that the action of activin A is to cause small preantral follicles to become dormant at the preantral stage. To investigate the role of secondary follicles in early folliculogenesis, small preantral follicles were cocultured with secondary follicle (300-350 microm in diameter) in the presence of FSH. The secondary follicle showed a significant increase in follicular diameter as a result of stimulation by FSH, but the small preantral follicles did not increase in size. After removal of the secondary follicle, however, the small preantral follicles commenced follicular growth, indicating that the growth of small preantral follicles is suppressed by the secondary follicle. Administration of the activin binding protein follistatin caused a significant increase in follicular diameter of both small preantral and secondary follicles as a result of stimulation by FSH. These results have suggested that secondary follicles cause primary follicles to become dormant at the resting stage by secreting activin.

Activins↗

PubMed2003

The early stages of follicular development: activation of primordial follicles and growth of preantral follicles.

Although enormous progress has been made in understanding the events and regulation of the later stages of ovarian follicular development, the early stages of development, to a large extent and particularly in large mammals, remain a mystery. Mechanisms that regulate the initiation of follicular growth (follicle activation) and the ensuing growth and differentiation of preantral follicles are of considerable interest, since their elucidation is a prerequisite to use of the primordial pool to enhance reproductive efficiency in domestic animals, humans, and endangered species. This review is an attempt to summarize the approaches that have been taken to further this goal and the results thus far of these efforts. Preantral follicular development can be divided into three stages: activation of primordial follicles, the primary to secondary follicle transition, and the development of secondary follicles to the periantral stage. The activation of primordial follicles in vitro has been achieved thus far in rodents, cattle, and primates, where it occurs spontaneously without the addition of growth factors or hormones. The ovaries of rodents are small enough to be cultured intact and, in that experimental situation, some follicles activate, while many remain in the resting pool, and the addition of specific factors can increase or decrease the number of follicles that leave the resting pool in vitro. In contrast, follicular activation in cattle and primates has been studied by culturing small pieces of the ovarian cortex, rich in primordial follicles, and the great majority of the primordial follicles activate in that situation, suggesting the importance of inhibitory factors to the normal, gradual exit of follicles from the resting pool. In cultured rodent ovaries, follicles appear to pass easily and spontaneously from the primary to the secondary stage, whereas few of the activated follicles in cultured cortical pieces from cattle or primates progress from the primary to the secondary stage. Understanding the requirements for the primary to secondary transition is critical for growing follicles activated in vitro to the late preantral and antral stages. In contrast, the requirements for the continued growth of larger preantral follicles, which can be isolated for in vitro studies, have been extensively explored in rodents and to a lesser extent in domestic species. A number of hormones and factors have been implicated and will be discussed. Taken together, the results highlight the need for a better understanding of the earliest stages of follicular development in domestic ruminants, particularly follicle activation and the primary to secondary follicle transition.

Activins↗

PubMed2002

Gap junctional intercellular communication of bovine granulosa and thecal cells from antral follicles: effects of luteinizing hormone and follicle-stimulating hormone.

Throughout each estrous cycle, the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), are involved in regulation of folliculogenesis. We have shown that LH or FSH affect cellular interactions mediated by gap junctions in bovine granulosa and thecal cells in vitro. To evaluate further the hypothesis that gonadotropins influence gap junctional intercellular communication (GJIC) and expression of gap junctional proteins known as connexins (Cx), throughout antral follicle development, granulosa and thecal cells from large (>10 mm; n = 13), medium (5-10 mm; n = 20), and small (<5 mm; n = 27) follicles were cultured (n = 4 cultures per size) with or without LH, FSH, or LH + FSH for 24 h. GJIC was evaluated (n = 125-150 cells/treatment group) by using the fluorescent recovery after photobleaching technique and laser cytometry. Additionally, Cx43, Cx32, and Cx26 were detected in cultured cells by immunocytochemistry and Cx43 by Western immunoblot analysis. Finally, progesterone production by cultured cells was evaluated by radioimmunoassay. Across all follicles and treatments, GJIC was greater (p < 0.01) for granulosa than thecal cells (4.9 +/- 0.05 vs 3.8 +/- 0.04%/min). For granulosa cells of large and medium follicles, LH and/or FSH did not affect GJIC. For granulosa cells of small follicles, FSH increased (p < 0.05), but LH or LH + FSH had no effect on GJIC. For thecal cells of large follicles, LH increased (p < 0.01) GJIC, whereas FSH or LH + FSH had no effects. For thecal cells of medium and small follicles, LH and/or FSH did not affect GJIC. These results demonstrate that FSH influenced GJIC of granulosa cells from small, but not from medium or large, follicles, and LH influenced GJIC of thecal cells from large, but not from medium or small, follicles. Cx43 was present as punctate staining between granulosa or thecal cells from all cultures, indicating assembled gap junctions. LH + FSH increased (p < 0.05) expression of Cx43 only by thecal cells from large follicles. Cx32 was detected in the perinuclear cytoplasm of cultured granulosa or thecal cells, and in the cytoskeleton of a few cells per culture dish in all sizes of follicles. Cx26 was present in a regular pattern throughout the cytoplasm of granulosa or thecal cells in all sizes of follicles. For granulosa cells from large follicles, progesterone production was stimulated (p < 0.05) with LH or FSH alone but was unaffected by LH + FSH. For granulosa cells from medium and small follicles, progesterone production was unaffected by LH and/or FSH. For thecal cells from all sizes of follicles, LH, FSH, and LH + FSH stimulated (p < 0.05) production of progesterone. These data indicate that LH and FSH influence gap junction function and expression, which likely contributes to the development and maintenance of ovarian follicles.

3-Hydroxysteroid Dehydrogenases↗

PubMed1983

Adenylyl cyclase system of the small preovulatory follicles of the domestic hen: responsiveness to follicle-stimulating hormone and luteinizing hormone.

The purpose of this study was to determine if the granulosa cells of the small preovulatory follicles of the domestic hen are a target tissue for follicle-stimulating hormone (FSH). The third largest (F3), fourth largest (F4), and fifth largest (F5) follicles were removed from hens at 20, 12, 6 and 2 h before ovulation of the F1 follicle. Basal, FSH- and luteinizing hormone (LH)-stimulable adenylyl cyclase (AC) activities were measured in the granulosa cells. Isolated granulosa cells of the F5 follicle, obtained 20 h before ovulation of the F1 follicle, were incubated with ovine (o) or turkey (t) FSH and progesterone (P4) was assayed in the medium. Basal AC activity was similar for F5, F4 and F3 granulosa cells except for an increase (P less than 0.01) in F3 follicles removed 2 h before ovulation of the F1 follicle. The FSH-stimulable AC activity of F5, F4 and F3 granulosa cells was elevated over basal (P less than 0.01). The greatest responsiveness was seen in the F5 follicle and the least in the F3 follicle. LH-stimulable AC activity was absent in the F5 follicle but present in the F4 and F3 follicles with the greater responsiveness in the F3 follicle. Isolated F5 granulosa cells secreted significant amounts of P4 in response to oFSH and tFSH. The data indicate that: 1) FSH stimulates the AC system of granulosa cells of the smaller preovulatory follicles (F5 greater than F4 greater than F3) while LH stimulates the AC system of granulosa cells of the larger follicles (F3 greater than F4), and 2) FSH promotes P4 production by granulosa cells of F5 follicles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗