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Male and female genotype mediate pheromonal regulation of the mouse estrous cycle.

Estrous cyclicity was studied to examine the possibility that strain differences in the regularity of the mouse estrous cycle are the result of different olfactory signals produced by the male. Females with regular estrous cycles (lines E and S1) were housed in the olfactory presence of males from a line with irregular cycles (line CN-) or in the presence of males of their own line (used as a control). Females with irregular cycles (line CN-) were housed in the presence of males from a line with regular cycles (line E) or were exposed to males of their own line. The regularity of the estrous cycle decreased in line E females (regular cycles) when exposed to line CN- males (irregular cycles). The decreased regularity of line E cyclicity resulted from an increased period of diestrus, i.e., lengthening of the cycle. In contrast, line S1 females (regular cycles) did not show any change in estrous cyclicity when exposed to line CN- males. The period of diestrus increased in line CN- females when they were exposed to line E males. These results provide evidence that 1) the genotype of the male can influence the regularity of the estrous cycle, and 2) the genotype of the female regulates her responsiveness to environmental factors (e.g., male odor).

Aging↗

Immunotoxicologic effects of ethylene dibromide in the mouse and their modulation by the estrous cycle.

Estrous cycle modulation of immunologic sensitivity to ethylene dibromide (EDB) was studied in addition to toxicologic end points. Female B6C3F1 mice were injected intragastrically with 31.25, 62.5, or 125 mg/kg EDB for 5 days a week for 12 weeks. Vaginal smears determined the estrous cycle. At 125 mg/kg there were decreases in hemoglobin and hematocrit and longer estrous cycles (5.5 vs 4.3 days, p = 0.006), and increases in cholesterol, triglycerides, total protein, and albumin. The negative dose response seen for T- and B-cell mitogenesis around metestrus was absent for mice near estrus. The high dose of EDB prolonged intervals between estrus, was immunotoxic and immunosuppressive.

Animals↗

Serum hormones during the estrous cycle and estrous behavior in heifers after administration of propylthiouracil and thyroxine.

Two experiments were conducted to assess the characteristics of thyroid-stimulating hormone (TSH) during the estrous cycle and to examine the effects of experimentally altered thyroid status on estrous behavior and hormonal concentrations in heifers. In Exp. 1, normal profiles of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and TSH were examined on days 2, 12, and 19 of the estrous cycle (day 0 = estrus) in six Holstein heifers. Baseline concentrations of LH were 1.5- to 2.1-fold higher on day 2 (P = .07) and day 19 (P < .01) than on day 12. Pulse frequency of LH was higher (P < .05) on days 12 and 19 than on day 2. For FSH, baseline concentrations were similar on all 3 d, but pulse frequency was higher (P < .05) on day 19 than on day 2 or day 12. Overall and baseline concentrations of TSH were similar on all 3 d. Pulse frequency of TSH was higher (P < .05) on day 12 than on day 19, but both were similar to that on day 2. In Exp. 2, secretion of TSH in Holstein heifers was altered by administering (i.v.; one-half of the daily dose given twice daily) either phosphate-buffered saline (SAL; n = 6), propylthiouracil (PTU; 20 mg/100 kg body weight [BW]; n = 6), or T4 (1 mg/100 kg BW; n = 5) from day 4 until the next estrus. Duration of estrous cycles during and after treatments, percentages of heifers exhibiting estrus, BW, and average daily gain were unaffected by treatment. Concentrations of TSH were higher (P < .05) in the afternoon than in the morning and higher (P = .06) in PTU heifers than in T4 heifers. Treatment with T4 during the treatment estrous cycle and for up to 6 d into the next estrous cycle increased (P < .01) concentrations of T4 and T3 compared to SAL and PTU. Treatment with PTU during the treatment cycle increased concentrations of T4 (P < .05) and TSH (P = .06) compared to SAL. We conclude that TSH secretion was pulsatile, demonstrated a diurnal change, and varied inconsistently during the estrous cycle. Altering thyroid hormones and TSH secretion in heifers seemed to have no effect on estrous behavior or estrous cycles.

Animals↗

Tissue concentrations of mast cells and lymphocytes of the bovine uterine tube (oviduct) during the estrous cycle.

Estrous cycle fluctuations in the mast cell and lymphocyte counts (per mm2 of tissue) of the ampulla and isthmus of the bovine uterine tube (oviduct) were determined. Four random sections of each region of the uterine tube were prepared at 2 micron thickness and stained with toluidine blue. The mast cell count of the isthmus was found to be significantly higher (P less than 0.01) than the mast cell count of the ampulla for all stages of the estrous cycle. A significant increase (P less than 0.01) in the mast cell value of the isthmus occurred during metestrus, diestrus, and proestrus. In the ampulla, metestrous and diestrous mast cells numbers were significantly higher (P less than 0.05) than mast cell numbers during estrus. The lymphocyte numbers remained relatively constant in both the ampulla and the isthmus except during diestrus, when ampullary lymphocyte numbers increased significantly (P less than 0.05). Lymphocytes were observed to migrate through the uterine tube epithelium and mast cells were observed only in the lamina propria.

Animals↗

[Changes in the nature of the estrous cycle and gametogenesis during superovulation stimulation in rats at different stages of the cycle].

Estrous cycle, ovulation rate and gamete quality were studied in rats with superovulation induced on different days of the cycle. It was shown that the rat ovaries in estrous were most sensitive to the action of gonadotropins. Heterogeneity in the ovulation rate was noted in animals at the same phase of the cycle. There was a relative increase in the number of gametes with chromosomal alterations in experimental rats, with the value depending on the stage of the cycle when PMS was injected. The study of the estrous cycle in rats with superovulation induced on different days of the cycle has revealed strong hormonal influences on the sequence of stage alterations.

Animals↗

Lectin histochemistry of mouse vagina during the estrous cycle.

Estrous cycle-related histochemical changes in the vaginal epithelium of sexually mature female mice were studied with 30 fluorescein isothiocyanate (FITC)-labeled lectins. On the basis of the staining pattern the lectins were divided into five groups: I, seventeen lectins that reacted with mucinous surface layer of proestrus. This group comprised two subgroups: Ia, seven lectins that reacted exclusively with the mucinous layer, and Ib, ten lectins that reacted with mucinous cells and the underlying squamous epithelium of proestrus; II, two lectins that reacted with squamous epithelium of proestrus only but were unreactive with mucinous cells; III, three lectins that reacted in a phase-specific manner with squamous epithelium; IV, six lectins that showed increased luminal surface reactivity in diestrus and/or metestrus; and V, eleven lectins that were unreactive with vaginal epithelium. These data indicate that the cyclic changes in the morphology of the vaginal epithelium are accompanied by distinct lectin reactivity patterns.

Animals↗

Do Norway rats (Rattus norvegicus) synchronize their estrous cycles?

Estrous synchrony was tested using 10 pairs of sibling female rats (Rattus norvegicus). A Monte Carlo bootstrap simulation was used to construct random control groups to avoid previous statistical errors and to test for significance when there are irregular cycles. The 10 pairs of females did not exhibit estrous synchrony. The effect of cycle irregularity on the limits of synchrony was analyzed using an equation that the related degree of cycle regularity to the degree of synchrony. This equation significantly predicted the limits of synchrony: cycle irregularity limits both the maximum and minimum degree of synchrony that can occur between two females. Finally, simulations of the expected levels of synchrony in groups of five rats were compared to the original study on estrous synchrony. The simulations indicated that the results of the original study were consistent with chance levels of synchrony. It is concluded that there is no evidence that Norway rats synchronize their estrous cycles. Evolutionary implications are discussed.

Algorithms↗

Short estrous cycles and estrous signs after premature ovulations induced with cloprostenol and gonadotropin-releasing hormone in cyclic dairy cows.

The aim of the present study was to confirm earlier findings, obtained with a small number of animals, that gonadotropin-releasing hormone (GnRH) can shorten corpus luteum functional life when it is administered 24 h after cloprostenol (PG) treatments given 7-9 days after estrus. In addition, the effects of two treatments, PG alone or PG + GnRH given before mid-diestrus, on signs of estrus were studied. Sixty cows in farm conditions were used in the experiment. Eight days after natural estrus, they were given an intramuscularly (i.m.) treatment of cloprostenol (0.5 mg). The animals were then divided into two groups. One group (n = 25) received an i.m. treatment of gonadorelin (0.1 mg) 24 h after the PG treatment (PG + GnRH group), while another group (n = 35) served as controls without any further treatment (PG group). Estrous signs were recorded. Progesterone concentrations were measured from samples of whole milk. No short cycles were observed in the PG group, whereas 33% of the cows in the PG + GnRH group exhibited premature luteal regression (P < 0.05). Cloprostenol treatment on Day 8 had no effect on the intensity of the estrous signs. Instead, GnRH treatment 24 h after PG treatment weakened the estrous signs significantly (P < 0.01). It is concluded that GnRH administration 24 h after a PG treatment given 8 days after estrus can cause short estrous cycles in some cows on an individual basis.

Animals↗

A Markov chain model for animal estrous cycling data.

Estrous cycling data contain sequences of characters (e.g., DPEMD). Each sequence represents an animal's estrous cycle, with each character indicating the daily estrous cycle stage. Changes in the estrous cycle pattern, which is determined by estrous stage lengths, can provide information on adverse events. Stage lengths are not directly observable. However interval censored lengths for all but the first and the last stages in a sequence can be extracted from the data. We propose a Markov chain model to approximate the estrous cycling process. The transition probabilities from one stage to another can be derived by conditioning on stage lengths. Assuming Weibull distribution for stage lengths, with the second Weibull parameter depending upon treatment effects and animal-specific random effects, regression models on censored stage lengths are fitted. A Bayesian approach is used for inference on dose effects. The analysis is implemented with MCMC method in WinBUGS. An estrous cycling data set from a National Toxicology Program study is analyzed as an example.

Animals↗

Estrous cycle regulation of mammary epithelial cell proliferation, differentiation, and death in the Sprague-Dawley rat: a model for investigating the role of estrous cycling in mammary carcinogenesis.

The Sprague-Dawley rat is highly regarded for studies designed to investigate the effects of endocrine modulation on mammary carcinogenesis. In this study, we further evaluate the validity of the Sprague-Dawley rat model for the study of human breast cancer by evaluating the effects of normal 4-day estrous cycling on mammary epithelial cell proliferation, differentiation, and apoptotic death. Trends in mammary gland development with stage of 4-day estrous cycle were evident. Mammary glands isolated from follicular and early luteal stages had predominantly ductal histoarchitecture, whereas glands isolated from mid-late luteal were predominantly lobuloalveolar. Quantitation of BrdU incorporation revealed that epithelial cell proliferation was eight-fold higher in metestrus and diestrus-1 than in proestrus. Expression of beta-casein and whey acidic protein (WAP)4 mRNA was also highly dependent on stage of estrous, with detection restricted to midcycle. Apoptotic cell death of mammary epithelium was found to be suppressed during the peak in cell proliferation. TRPM-2/ clusterin mRNA was elevated when apoptosis was low and milk protein mRNA levels were high, consistent with putative roles for TRPM-2/clusterin in inhibiting cell death in regressing tissues and inducing mammary epithelial cell differentiation. Cell proliferation, differentiation, and death occurred only in a subset of epithelial cells per estrous cycle, and these cells appeared randomly distributed throughout multiple ductules and alveoli. These observations suggest that cellular response(s) to ovarian hormone-dependent signals is asynchronous. Cumulatively, these observations demonstrate that rat mammary epithelial cell proliferation, differentiation, and death are under the control of cycling ovarian hormones, similarly to the human mammary epithelium during the menstrual cycle.

Animals↗

Changes in the distribution of ZO-1, occludin, and claudins in the rat uterine epithelium during the estrous cycle.

During the estrous cycle, the endometrium epithelium experiences marked cellular structural changes. For fertilization to proceed, maintenance of an adequate uterine environment by ovarian hormones is essential. Epithelial cells lining the uterine lumen are associated with each other by tight junctions (TJs), which regulate the passage of ions and molecules through the paracellular pathway. The aim of the present study was to assess by confocal immunofluorescence the distribution pattern of the TJ proteins ZO-1, occludin, and claudins 1-7 in the rat uterus during the estrous cycle. Our results reveal that on proestrus, the day when mating takes place, ZO-1, occludin, and claudins 1 and 5 are located in the TJs, while claudins 3 and 7 display a basolateral distribution. In contrast, on metestrus day, when no sexual mating occurs and the uterine lumen is devoid of secretions, none of these proteins were detected in the TJ region, and only a diffuse cytosolic staining was observed for some of the proteins. On estrus and diestrus days, an intermediate situation was encountered, since ZO-1 localized in the TJs, whereas occludin was no longer detectable in the TJs. The distribution of claudins during these stages varied from the lowermost portion of the basolateral membrane to its apex. In conclusion, the results show that the protein composition of TJs present in the luminal epithelial cells of the uterus changes during the different days of the estrous cycle, and suggest that the expression of TJ proteins participates in providing an adequate environment for a successful fertilization.

Animals↗

Effect of prostaglandin F2alpha dosage and stage of estrous cycle on the estrous response and corpus luteum function in beef heifers.

Ninety-five normal cyclic crossbred beef heifers were used to determine if the proportions of heifers showing estrus, intervals to estrus and corpus luteum (CL) function were influenced by PGF2alpha dosage and (or) the stage of luteal phase when PGF2alpha was administered. Heifers were assigned randomly to treatments in a 4x3 factorial arrangement. Treatments were 5, 10, 25 or 30 mg PGF2alpha injected either in early (5 to 9 d), mid (10 to 14 d) or late (15 to 19 d) stages of the luteal phase. Jugular samples were taken at 0 h and at 8 h-intervals for 48 h and again at 60 h after PGF2alpha treatment for progesterone assay. Heifers were observed for estrus continuously for 120 h PGF2alpha treatment. The proportion of heifers showing estrus was dependent upon (P<0.05) both dosage of PGF2alpha and stage of luteal phase. Heifers given 5 mg of PGF2alpha showed estrus only if treated during the late stage, while those given 10 mg of PGF2alpha showed a progressive increase of heifers in estrus as stage of luteal phase advanced. The proportion of heifers showing estrus after 25 and 30 mg of PGF2alpha increased from 56% for the early stage to 100% for the mid and late stages. Interval to estrus in heifers showing estrus within 120 h after PGF2alpha treatment did not differ (P>0.05) among dosages but tended (P=0.10) to be longer in heifers treated during the mid luteal stage (67 h) than in heifers treated in the two other stages (56 h). A greater proportion of heifers (P<0.05) showed estrus by 60 h after PGF2alpha when treated during the early and late luteal stages (75.5%) than for heifers treated during the mid luteal stage (30.4%). Patterns of progesterone concentrations were influenced (P=0.08) by the three way interaction of dosage, stage and time. In heifers that showed estrus, rate of decline in progesterone tended (P=0.07) to be slower during the mid luteal stage than during the early and late stages. Progesterone did not drop below 1 ng/ml until 32 h in heifers treated during the mid luteal stage; whereas progesterone dropped below 1 ng/ml by 24 h in heifers treated during the early and late stages. These data may be useful in designing more efficient systems for using PGF2alpha or its analogues in estrus synchronization of beef cattle.

Journal Article↗

In vitro LHRH release from superfused hypothalamus as a function of the rat estrous cycle: effect of progesterone.

The present study examines the effect of progesterone (P) on in vitro LHRH release from hypothalamic fragments from intact adult rats throughout the estrous cycle. Estrous cyclicity was monitored by daily vaginal smears, and animals which exhibited at least two consecutive 4-day estrous cycles were used. Animals were sacrificed between 10.00 and 13.00 h and the mediobasal hypothalamic-preoptic area-suprachiasmatic nucleus units were removed and transferred into superfusion chambers (one unit/chamber). Following a 2-hour control period, in which the spontaneous LHRH release was established, P (10 ng/ml) was infused in an intermittent mode (10 min-on, 20 min-off). Effluents were collected at 10-min intervals and LHRH concentrations were determined by RIA. The spontaneous LHRH release from control preparations was episodic throughout all stages of the estrous cycle with a significant low release rate and low LHRH amplitude only during estrus. Interestingly, intermittent infusion of P significantly stimulated LHRH release solely in hypothalamic fragments derived from proestrous rats. The P-stimulated LHRH release during the 1st-hour period after P infusion was significantly higher (p less than 0.05) than that observed in the control preparations during the same time period as well as from its own basal pre-P values (1-hour post-P: 4.26 +/- 0.96 vs. 1-hour control and pre-P: 2.34 +/- 0.38 and 2.32 +/- 0.57 pg/10 min, respectively). P administration did not stimulate in vitro LHRH release during the other stages of the estrous cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Central vs. peripheral metabolic control of estrous cycles in Syrian hamsters. II. Glucoprivation.

Estrous cycles in Syrian hamsters are inhibited by food deprivation or treatment with pharmacological inhibitors of intracellular glucose utilization (glucoprivic treatments). These same metabolic challenges increase neural stimulation in areas of the caudal brain stem thought to be involved in detection of metabolic signals. Experiment 1 was designed to examine whether vagally transmitted signals are important for glucoprivic effects on estrous cycles and on neural stimulation in the caudal brain stem. Vagotomized or sham-operated hamsters were treated with 2-deoxy-D-glucose (2-DG) at a dose known to decrease cellular glucose utilization and inhibit estrous cycles (1,750 mg/kg). Vagotomized and sham-operated hamsters did not differ significantly in incidence of 2-DG-induced anestrus or in neural stimulation in the caudal brain stem, but the effects of 2-DG on estrous cycles and neural stimulation appeared to have been attenuated in vagotomized hamsters. In experiment 2, hamsters were injected intracerebroventricularly with 2-DG or glucose at doses that did not induce anestrus when injected systemically (125 and 250 mg/kg). Groups treated with intracerebroventricular injections of 2-DG showed a significantly higher incidence of anestrus than those treated with glucose. In experiment 3, effects of systemic injections of 2-DG were prevented by prior injection of glucose or fructose at the same concentration, indicating that 2-DG acts via effects on glucose metabolism, rather than via a nonspecific pharmacological effect or generalized stress response. Results of these experiments and those reported elsewhere (J. E. Schneider, A. J. Hall, and G. N. Wade. Am. J. Physiol. 272 (Regulatory Integrative Comp. Physiol, 41) R400-R405, 1997] are consistent with the notion that central glucoprivation is sufficient, whereas peripheral lipoprivation is not critical, for metabolic effects on estrous cycles.

Anestrus↗