Effects of thymulin on spontaneous puberty and gonadotrophin-induced ovulation in prepubertal normal and hypothymic mice.
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The effects of thymulin administration beginning on days 19 or 24 of age on spontaneous puberty and gonadotrophin-induced ovulation were analysed in female normal and hypothymic mice. In normal and hypothymic mice, the daily administration of thymulin at 24 days of age resulted in a delay in the age of vaginal opening, with an increase in serum progesterone levels. Normal mice treated with 200 ng thymulin beginning on day 19 of age and injected with pregnant mare serum gonadotrophin (PMSG) 24 h later had an increase in ovulation rate, number of ova shed and weight of the ovaries. None of the hypothymic mice treated with thymulin on day 19 and PMSG on day 20 ovulated. PMSG treatment on day 25 induced ovulation in hypothymic mice. When these animals were injected previously with 200 ng thymulin, the number of ova shed by ovulating animals was lower than in PMSG-treated animals. Administration of thymulin and sequential injection of PMSG and human chorionic gonadotrophin 54 h later resulted in an increase in ovulatory response in comparison with those receiving only PMSG. The results suggest that thymulin plays a role in the regulation of spontaneous puberty through its effects on adrenal and ovarian endocrine functions. The increase in the ovarian PMSG response-treated animals, previously given thymulin, showed that this thymic hormone participates in the regulation of gonadotrophin secretion mechanisms and seems to be dose- and age-dependent. In hypothymic mice, neuroendocrine mechanisms regulating puberty are different from those of normal mice. (+info)
A selective increase in circulating inhibin and inhibin pro-alphaC at the time of ovulation in the mare.
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The relationship between a selective increase in circulating immunoreactive (ir)-inhibin and the time of ovulation was investigated in mares. Concentrations of plasma ir-inhibin were measured every 4 h during the periovulatory period. Inhibin pro-alphaC, a precursor protein of the inhibin alpha-subunit, was also measured. The changes in ir-inhibin and inhibin pro-alphaC in circulation were parallel. Concentrations of both ir-inhibin and inhibin pro-alphaC in the plasma increased at the same time when ovulatory follicles ruptured, and the peak levels of circulating ir-inhibin and inhibin pro-alphaC were maintained for 4-8 h. There was no selective increase in plasma concentrations of estradiol-17beta during the process of ovulation. These results suggest that the selective increase in ir-inhibin and inhibin pro-alphaC was caused by the absorption of follicular fluid after the rupture of ovulatory follicles. These results also suggest that the measuring of plasma concentrations of ir-inhibin or inhibin pro-alphaC in mares might be a useful method for detecting the time of ovulation. (+info)
Sister chromatid exchanges, chromosome aberrations and micronuclei in female lymphocytes: correlations with biological rhythms, miscarriages and contraceptive pill use.
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Our study looked at the variation in peripheral blood lymphocytes, during the menstrual cycle, of frequencies of sister chromatid exchanges (SCE) and micronuclei (MN) in 819 women and cells with aberrant chromosomes (CA) in a selected sample of 136 volunteers. We observed significant fluctuations in SCE and CA frequencies: SCEs reached a maximum value at the end of menstruation and a low at the time of ovulation, whereas CAs showed a continuous increase from the beginning of the menstrual cycle up to the time of ovulation and a progressive decrease thereafter. MN frequency did not fluctuate in a statistically significant way. No statistically significant differences in SCE, CA and MN frequencies were observed when fertile women were compared with women taking the contraceptive pill or those in menopause and no difference was found between women who had undergone physiological or surgically induced menopause. Moreover, no difference was found between women with a history of miscarriages and matched controls. These data together suggest that the natural variations in sexual hormone levels, but not those due to the contraceptive pill or their reduction at menopause, can contribute in modulating the baseline frequencies of SCEs and CAs. Moreover, these data suggest that the increased risks either of producing a chromosome imbalance in the progeny (eliciting miscarriages) or of occurrence of gynaecological diseases is not predictable by evaluating cytogenetic end-points in peripheral blood lymphocytes. (+info)
Administration of progesterone to cows with ovarian follicular cysts results in a reduction in mean LH and LH pulse frequency and initiates ovulatory follicular growth.
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Cows with ovarian follicular cysts were treated with progesterone to determine whether a reduction in LH concentrations and initiation of ovulatory follicular waves would occur. Cysts were diagnosed using transrectal ultrasonography when single follicular structures > 20 mm or multiple structures > 15 mm in diameter were present for 7 d in the presence of low progesterone concentrations. Three groups were studied: 1) cows with normal estrous cycles (CYC, n = 8); 2) cows with untreated cysts (CYST, n = 7); and 3) cows with cysts treated with two progesterone-releasing intravaginal devices (PRID, n = 8) for 9 d. Ovaries were examined with transrectal ultrasonography, and blood samples were collected daily for analysis of progesterone and FSH. Serial blood samples for determination of mean LH and LH pulse frequency were collected on d 0 (CYST and PRID cows only), 1, 5, 9, and 10. Progesterone concentrations were higher in PRID cows than in CYST cows throughout the PRID treatment period (P < .002). On d 0, LH pulse frequency was similar (P = .10) in PRID (6.6+/-.6 pulses/8 h) and CYST cows (5.1+/-.6 pulses/8 h), but mean LH tended to be higher (P = .054) on d 0 in PRID cows (2.5+/-.2 ng/mL) than in CYST cows (1.9+/-.2 ng/mL). Mean LH and LH pulse frequency decreased (P < .002) by d 1 in PRID cows (1.1+/-.2 ng/mL, 1.8+/-.6 pulses/8 h) compared with CYST cows (2.1+/-.2 ng/mL, 5.6+/-.6 pulses/8 h) and remained lower throughout most of the experimental period. The FSH concentrations were higher (P < .01) in PRID cows than in CYC and CYST cows on d 3 and 4. The increase in FSH concentrations preceded emergence of the PRID-induced follicular wave. All PRID cows and four of seven CYST cows initiated new follicular waves during the period of PRID treatment. Follicular waves were initiated later (P < .05) in CYST cows (d 5.2+/-1.7) and PRID cows (d 5.5+/-.6) than in CYC cows (d 1.8+/-.3). Cysts were smaller (P < .01) at the end of the treatment period in PRID cows compared with CYST cows. No CYST cows ovulated, but all PRID cows ovulated newly developed follicles 3 or 4 d after PRID removal. Treatment with exogenous progesterone reduced LH in cows with cysts, and this was followed by development of normal ovulatory follicles. (+info)
Role of luteinizing hormone in follicle deviation based on manipulating progesterone concentrations in mares.
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The effects of several doses of progesterone on FSH and LH concentrations were used to study the role of the gonadotropins on deviation in growth rates of the two largest follicles during the establishment of follicle dominance. Progesterone was given to pony mares at a daily dose rate of 0 mg (controls), 30 mg (low dose), 100 mg (intermediate dose), and 300 mg (high dose). All follicles > or = 6 mm were ablated at Day 10 (Day 0 = ovulation) to initiate a new follicular wave; prostaglandin F(2alpha) was given to induce luteolysis, and progesterone was given from Days 10 to 24. The low dose did not significantly alter any of the ovarian or gonadotropin end points. The high dose reduced (P < 0.05) the ablation-induced FSH concentrations on Day 11. Maximum diameter of the largest follicle (17.2 +/- 0.6 mm) and the second-largest follicle (15.5 +/- 0.9 mm) in the high-dose group was less (P < 0.04) than the diameter of the second-largest follicle in the controls (20.0 +/- 1.0 mm) at the beginning of deviation (Day 16.7 +/- 0.4). Thus, the growth of the two largest follicles was reduced by the high dose, presumably through depression of FSH, so that the follicles did not attain a diameter characteristic of deviation in the controls. The intermediate dose did not affect FSH concentrations. However, the LH concentrations increased in the control, low, and intermediate groups, but then decreased (P < 0.05) in the intermediate group to pretreatment levels. The LH decrease in the intermediate group occurred 2 days before deviation in the controls. The maximum diameter of the largest follicle was less (P < 0.0001) in the intermediate group (27.3 +/- 1.8 mm) than in the controls (38.9 +/- 1.5 mm), but the maximum diameter of the second-largest follicle was not different between the two groups (19.0 +/- 1.1 vs. 20.3 +/- 1.0 mm). Thus, the onset of deviation, as assessed by the second-largest follicle, was not delayed by the decrease in LH. Diameter of the largest follicle by Day 18 in the intermediate group (23.1 +/- 1.6 mm) was less (P < 0.05) than in the controls (28.0 +/- 1.0 mm). These results suggest that circulating LH was not involved in the initiation of dominance (inhibition of other follicles by the largest follicle) but was required for the continued growth of the largest follicle after or concurrently with its initial expression of dominance. (+info)
Tumor necrosis factor alpha regulates collagenolytic activity in preovulatory ovine follicles: relationship to cytokine secretion by the oocyte-cumulus cell complex.
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The pleiotropic cytokine tumor necrosis factor (TNF)-alpha has been implicated in the mechanism of ovulation. Experiments were designed to test the hypothesis that TNF-alpha secreted from the oocyte-cumulus cell complex stimulates follicular collagenase production and thereby contributes to ovarian wall degradation and ovulatory rupture. Proestrous ewes were treated with GnRH to synchronize the onset of the gonadotropin surge; ovulation occurs approximately 24 h later. There was an increase in TNF-alpha (immunoassay) in antral fluid of preovulatory follicles at 18 h after GnRH, which was related to tissue collagenolytic bioactivity (radiolabeled type I substrate digestion by enzymatic extract) and collagen (hydroxyproline) depletion. Intrafollicular injection of TNF-alpha antibodies at 12 h after GnRH negated the rise in follicular collagenolytic bioactivity (and is known to block ovulation in the sheep). Moreover, collagenase production was enhanced when follicular tissues (0 h GnRH) were incubated (6 h) with recombinant TNF-alpha; this effect was abolished by the transcriptional inhibitor actinomycin D. Secretion of TNF-alpha by oocyte-cumulus cell complexes isolated from preovulatory follicles simulated the in vivo circumstance. Immunostaining indicated that TNF-alpha was confined mainly to the oocyte before GnRH administration, accumulated in cumulus cells during the mid-to-late preovulatory period, and was expended with the imminent approach of ovulation. To our knowledge, this is the first report specifying that up-regulation of collagenase expression is a target mode of TNF-alpha action in preovulatory follicles. The oocyte-cumulus cell complex is an apparent source of soluble TNF-alpha. (+info)
Effect of acute nutritional restriction on incidence of anovulation and periovulatory estradiol and gonadotropin concentrations in beef heifers.
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The effects of acute nutritional restriction on follicular dynamics, incidence of anovulation, and periovulatory estradiol and gonadotropin concentrations were studied in two replicates using beef heifers exhibiting regular estrous cycles. Heifers fed a diet supplying 1.2 maintenance (1.2 Mn) were synchronized using an intravaginal progesterone-releasing device for 8 days. One day before device removal, heifers were allocated randomly, within replicate, to a diet supplying 0.4 Mn (n = 20), or kept at 1.2 Mn (n = 21). On the sixth day after detected ovulation, heifers received 500 microg of synthetic prostaglandin F(2alpha) (PGF(2alpha)) to induce luteolysis, estrus, and ovulation of the first dominant follicle (DF). Animals were inseminated and returned to a diet of 1. 2 Mn. Pregnancy diagnosis was performed 30 days later. The maximum diameter subsequently attained by the DF present at progesterone withdrawal was smaller (P < 0.01) in heifers fed 0.4 Mn. Two heifers fed 0.4 Mn failed to ovulate this DF (P > 0.10). Growth rate (P < 0. 01) and maximum diameter (P < 0.001) of the DF in the first follicular wave of the next estrous cycle was also reduced in heifers fed 0.4 Mn. After prostaglandin administration, a further 10 heifers fed 0.4 Mn failed to ovulate the first DF of this cycle, and it regressed (P < 0.001), causing anovulation in 12 of 20 heifers within 13-15 days (P < 0.001). Anovulation of the DF present at progesterone withdrawal was preceded by a proestrous estradiol increase but absence of a gonadotropin surge (2 of 2 heifers), while neither endocrine event was detected before anovulation of the DF of the first new follicular wave (2 of 2 heifers). In cases in which ovulation of the first DF of the new cycle occurred, fertility was similar (P > 0.10) in heifers fed either 0.4 (n = 7) or 1.2 Mn (n = 20). In conclusion, acute nutritional restriction of cyclic heifers from 1.2 to 0.4 Mn decreased the growth rate and maximum diameter of DFs and induced failure of the DF to ovulate in 60% of heifers, but, within the confines of limited animal numbers, did not compromise fertility in heifers that ovulated. (+info)
Alterations of events related to ovarian function in tumor necrosis factor receptor type I knockout mice.
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C57BL6 mice with targeted disruption of tumor necrosis factor (TNF) type 1 receptor (TNFRI) exhibited early vaginal opening when compared with wild-type mice (Day 24 +/- 0.6, n = 10, vs. 28 +/- 0.2, n = 11, P < 0.001). Equine CG- and hCG-treated TNFRI null mice ovulated more ova than did controls at two distinct times during the prepubertal period (Day 21: 13.4 +/- 1.7 vs. 7.3 +/- 1.4, P < 0.05; Day 25: 20.7 +/- 2.7 vs. 13.0 +/- 1.3, P < 0.05). Enhanced responsiveness to gonadotropins was not observed in adult mice. At 6 mo of age only 40% of TNFRI null mice exhibited estrous cycles. Those TNFRI null mice with estrous cycles spent significantly more time in diestrus and less time in estrus than controls. TNFRI null mice delivered significantly fewer litters (P < 0.001) than did C57BL6 and TNFRII null mice (TNFRI null 2.59 +/- 0.39; C57BL6 4.91 +/- 0.57; TNFRII null 5.40 +/- 0.60 litters/mo/10 pairs over a 12-mo period). Ovarian dispersates prepared on Day 25 of age from control and TNFRI knockout mice were cultured with and without 10 ng TNF/ml. TNF inhibited LH-stimulated progesterone and estradiol secretion by control dispersates but had no effect on cAMP. In contrast, TNF did not affect LH-stimulated accumulation of progesterone, estradiol, or cAMP by ovarian dispersates from TNFRI knockout mice. The results indicate that lack of TNFRI enhances ovarian responsiveness to gonadotropins during the prepubertal period and may be related to early vaginal opening. The lack of TNFRI is associated with early senescence and poor fertility. These studies demonstrate that the mechanism of TNF-mediated inhibition of steroidogenesis is most likely via TNFRI. (+info)