Effects of estradiol and progesterone on early embryonic development in aging rats

Regularly cyclic, middle-aged female rats exhibit a decreased incidence of fertility, and those females that are fertile produce small litters. These decreases in fertility and litter size are associated with reduced numbers of normal blastocysts formed and implanted, suggesting that pre- and/or peri-implantation failures may be the causes for these aging-related reproductive declines. The present study examined the relationships and influence of circulating estradiol (E2) and progesterone (P) levels on early embryonic development and implantation in middle-aged rats. Serial blood samples obtained from cannulated, middle-aged pregnant rats revealed minor decreases in plasma P and increases in E2 levels during Days 2-4 of pregnancy, compared to young pregnant rats, resulting in significantly (p less than 0.001) decreased plasma P/E2 ratios. These alterations in endogenous hormone secretion in middle-aged pregnant rats were associated with fewer normal blastocysts on Day 5 of pregnancy and reduced numbers of normally implanting embryos. Correlation analysis further revealed a significant (p less than 0.05) inverse relationship between mean circulating E2 levels and numbers of normal conceptuses on Day 12 of gestation. Moreover, s.c. administration of P implants (in Silastic) to middle-aged pregnant rats increased serum P levels by about 34-40 ng/ml, and significantly (p less than 0.05) reduced the incidence of abnormal embryos before implantation. In contrast, treatment with E2 minipumps produced a sustained rise in serum E2 (by about 7-15 pg/ml) and resulted in the complete absence of embryos in the reproductive tracts by Day 5 of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)     

An abnormal pattern of embryonic development during early pregnancy in aging rats

There is recent evidence that a decline in fertility and litter size precedes the cessation of regular estrous cyclicity in middle-aged female rats. This decline in litter size is related to a decrease in the number of normal blastocysts that are present on Day 5 of gestation, immediately prior to implantation. Thus, the pattern of embryonic development during the first 5 days of pregnancy may be altered in middle-aged rats, resulting in fewer implanting embryos and smaller litter sizes. The present study examined the ovulation rates, fertilization rates, and the patterns of embryonic development in regularly cyclic, young and middle-aged females during the first 5 days of pregnancy. Examination of the numbers of ovulated ova revealed that the ovulation rate was significantly reduced in 12- to 14-mo-old females (13 mo; 9.0 +/- 1.0/rat), but not in 9- to 11-mo-old females (10 mo; 12.2 +/- 0.8/rat), as compared to that in young animals (12.8 +/- 1.0/rat). However, there was no decrease in fertilization rate in either the 10-mo or 13-mo group. While the total numbers of embryos present on Days 2-5 were similar among all 3 groups, embryos from 10-mo females displayed a delayed pattern of development and an increased incidence of morphological abnormalities. These changes in embryo development were even more pronounced in the 13-mo group. By Day 5 of pregnancy there was a significant reduction in normal blastocysts in 10-mo (7.3 +/- 1.2/rat) and 13-mo (6.0 +/- 1.6/rat) rats, as compared to young females (10.6 +/- 0.9/rat).(ABSTRACT TRUNCATED AT 250 WORDS)     

The relation of ovarian steroid levels in young female rats to subsequent estrous cyclicity and reproductive function during aging

In multiparous rats, the incidence of regular estrous cyclicity and fertility decreases markedly at middle age. However, recent studies have shown that repeated pregnancies or progesterone (P) implants can subsequently cause retired breeder females to maintain regular cyclicity for an extended period of time; these results suggest a P-mediated deceleration of reproductive aging. In the present study, we examined the relation of ovarian steroid levels in young virgin females to their subsequent estrous cyclicity and reproductive function during aging as compared to multiparous females. Beginning at 4 mo of age and continuing to 6 mo of age, regularly cyclic virgin rats received either consecutive P implants (n = 41) or no implants (controls, n = 45) for 3 wk, followed by implant removal for 1 wk. Additional females (n = 72) were mated and allowed to undergo repeated pregnancies at 4, 6 1/2, and 8 mo of age. Blood samples were obtained throughout the estrous cycle (virgin females), during pregnancy (multiparous rats), and on Day 11 of successive treatments with P implants (virgins with P implants) for P, estradiol (E2), and testosterone (T) measurements. Subsequently, regularly cyclic females from all three groups were mated with fertile males to undergo term pregnancies at 10 and 12 mo of age. While the virgin controls showed cyclic increases in P, T, and E2 secretion during their estrous cycles, the P-implanted females had persistently low E2 and high P and T levels during treatment, which indicates an inhibition of ovarian E2 synthesis by P.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early treatment of young female rats with progesterone delays the aging-associated reproductive decline: a counteraction by estradiol

We have recently reported that successive treatments of young virgin rats with progesterone (P) implants produce elevated circulating P and consistently low estradiol (E2) concentrations, and subsequently delay the aging-associated reproductive decline. Inasmuch as E2 has been implicated in causing the loss of regular estrous cyclicity in aging rats, the present study examined if the concomitant presence of moderately increased circulating E2 levels could counteract the effects of P implants on reproductive aging. Starting at 3 1/2 mo and continuing to 8 mo of age, regularly cyclic, virgin rats received either s.c. Silastic implants of P (P-implanted), blank Silastic implants (virgin controls), or P + E2 implants (P + E2-implanted) for 3 wk, followed by implant removal for 1 wk. Each of these implant treatments was repeated in the same female rats 5 times. Blood samples were obtained on different days of the estrous cycle from the control group and on Day 11 of successive treatments with P or P + E2 implants for measurements of serum P and E2 values. At 8 1/2 and 10 mo of age, estrous cyclicity of these same virgin rats was again monitored, and 10-mo-old regularly cyclic females from each treatment group were mated with young fertile males to complete term pregnancies. While virgin controls showed cyclic increases in E2 and P secretion during the estrous cycle, P-implanted virgins exhibited consistently low serum E2 and moderately increased P levels during 5 successive treatments. The latter indicates a potent inhibition of ovarian E2 secretion by P implants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of vascular cannulation on serum concentrations of LH, FSH, prolactin and cortisol in prepubertal gilts

Two experiments were conducted to determine whether cannulation of the jugular vein in gilts alters serum concentrations of LH, FSH, prolactin (PRL) or cortisol (C). In Experiment 1, 12 crossbred prepubertal gilts weighing 95 +/- 1.3 kg were immobilized by snaring, and tygon tubing was threaded into the anterior vena cava through a 12-gauge needle inserted into the jugular vein. Five hours later, blood samples were drawn at 20-min intervals for 4 h (Day 0). Samples were also drawn at 20-min intervals for 4-h periods 24 h (Day 1) and 48 h (Day 2) after cannulation. Serum concentrations of LH were similar (P=0.26) among Day 0 (0.40 ng/ml), Day 1 (0.39 ng/ml) and Day 2 (0.34 ng/ml). Serum PRL was similar (P=0.07) among Day 0 (4.10 ng/ml), Day 1 (3.87 ng/ml) and Day 2 (3.43 ng/ml). Serum concentrations of C were greater (P < 0.001) on Day 0 (8.32 ng/ml) than Day 1 (4.48 ng/ml) or Day 2 (3.54 ng/ml). In Experiment 2, cannulas were placed in 29 prepubertal gilts. Two days after initial cannulation, six blood samples were drawn at 20-min intervals. Gilts were then immobilized by snaring, and a second cannulae was inserted into the contralateral vein. Five blood samples were taken at 2-min intervals during the second cannulation and then six samples were drawn at 20-min intervals. Serum LH and FSH were not altered by cannulation or elevated during the subsequent 2-h sampling period (P>0.05). In contrast, serum concentrations of PRL rose slowly (P<0.05) during cannulation and remained elevated for 60 min before returning to baseline. Serum concentrations of C rose within 6 min of cannulation, remained elevated for 30 min, and then declined over the next 90 min. From these two experiments, it appears that secretory patterns of LH and FSH can be accurately assessed immediately after cannulation in prepubertal gilts. Measurements of serum PRL and C that reflect nonstressed conditions, however, cannot be obtained until at least 2 h or 1 d after cannulation, respectively.     

Implantation delay and anti-deciduogenic activity in the rat by the anti-androgen, hydroxyflutamide

Studies were undertaken to determine whether the anti-androgen, hydroxyflutamide, has anti-progestagenic activity by using implantation, maintenance of pregnancy, and decidualization as end points. Prepubertal rats were induced to ovulate with the injection of 4 IU pregnant mare's serum gonadotropin and allowed to mate. Mated females were assigned randomly to various treatment groups. Beginning at 0800 h on Day 4 of pregnancy and at 12-h intervals thereafter, rats received a series of 6 s.c. injections of 5 mg hydroxyflutamide in oil, or oil only. Localized changes in endometrial vascular permeability, indicative of implantation, were assessed on Days 6 and 8 of pregnancy, after an injection of Evans blue dye. By Day 6, implantation has been initiated in the vehicle-treated rats, but not in hydroxyflutamide-treated rats. Hydroxyflutamide treatment was terminated on Day 6, and implantation was initiated by Day 8. The weights of uterine dye sites in hydroxyflutamide-treated rats on Day 8 were similar to those in vehicle-treated rats on Day 6. The number of fetuses and placentae were similar in all groups on Day 19. The weights of fetuses in both hydroxyflutamide-treated and hydroxyflutamide + progesterone-treated rats were similar and significantly lower than those in control rats. Although there were no significant differences between vehicle-treated or hydroxyflutamide-treated rats in the proportion of rats delivering and litter size, the hydroxyflutamide-treated rats delivered pups a mean of one day later than did the controls. Endometrial decidualization in ovariectomized, steroid-treated rats, following artificial stimuli, was significantly suppressed in hydroxyflutamide-treated rats compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential changes in the mechanisms controlling luteinizing hormone and prolactin secretion in middle-aged female rats

Serum luteinizing hormone (LH) and prolactin (PRL) concentrations were measured in young (3-4 month old) and middle-aged (10-12 month old) intact female rats on proestrus, in ovariectomized rats after two estrogen injections (estradiol benzoate; EB, 10 micrograms/100 g body weight, s.c.) or after preoptic stimulation in EB-primed ovariectomized rats. Only animals showing regular 4-day estrous cycles were selected for the experiment. The magnitude of proestrous LH surge was significantly smaller in middle-aged than in young rats. Two BE injections, at noon on Days 0 and 3, in ovariectomized middle-aged rats failed to induce surges in LH secretion on Day 4 whereas the same treatment produced LH surges in ovariectomized young rats. The preoptic electrochemical stimulation (50 microA for 60 sec) produced a prompt rise in serum LH levels in ovariectomized EB-primed young but not in middle aged rats. The preoptic stimulation with a larger current (200 microA) induced LH secretin in middle-aged rats. In none of these situations serum PRL concentrations were different between young and middle-age rats. These results suggest differential aging rates in the preoptic mechanisms governing LH and PRL secretion in the rat. The function of the preoptic ovulatory center in responding to the estrogen positive feedback action and inducing LH secretion may become impaired and independent of the PRL control mechanism, even before the regular estrous cycle terminates.     

Relation of parity and estrous cyclicity to the biology of pregnancy in aging female rats

In the female rat, the incidence of regular estrous cyclicity and fertility decreases progressively during aging, and the causes for these are unknown. To reveal the biology of pregnancy in aging rats, we performed a longitudinal study in a colony of multiparous rats bred every 2 mo. Beginning at 4 mo and continuing to 12 mo of age in these same individual females, we determined the chronological changes in estrous cyclicity, examined the relationship between the estrous cycle pattern and fertility, and recorded the numbers of live and dead pups delivered at term. In separate groups of 4- to 12-mo-old multiparous rats, we counted the number of ova present in the oviducts (ovulation rate) one day after mating and the number of grossly normal blastocysts found in the uteri on Day 5 of pregnancy. Similar studies were also performed in primiparous rats of 8, 10, and 12 mo of age. The cessation of regular cyclicity during aging occurred significantly (p less than 0.01) earlier in virgin than multiparous rats. Fertility followed a similar but more dramatic pattern of decline than did the incidence of regular cyclicity in both the multiparous and virgin females. Few irregularly cyclic and persistent-estrous females had fertile gestations after mating, and increasing proportions of regularly cyclic females also failed to reproduce successfully at middle age (8-12 mo). Thus, regular ovulatory cycles were essential but not sufficient for fertile gestations in aging rats. Beginning at 6 mo of age, the litter sizes of multiparous rats decreased progressively, and these decreases were associated with a similar decline in the number of live but not dead pups delivered. Also, the percentage of dead pups/total number of pups delivered increased steadily during aging in multiparous (from 14% to 69%) but not primiparous females. The litter sizes of 8- to 10-mo-old primiparous females were not different from those of multiparous rats. However, the litter sizes of irregularly cyclic rats were consistently smaller than those of regularly cyclic females. Thus, parity had little effect on fecundity in aging females, whereas the cessation of regular ovulatory cycles during aging greatly decreased both the incidence of fertility and the litter size.(ABSTRACT TRUNCATED AT 400 WORDS)     

Deceleration of age-associated changes in the preovulatory but not secondary follicle-stimulating hormone surge by progesterone

Recently, it has been reported that mating can delay the age-associated decline in reproductive function of female rats. Since circulating progesterone (P) levels are elevated for a 2- to 3-wk interval during pregnancy, the following study was conducted to determine whether intermittent elevation in P levels can alter the rate of reproductive aging in female rats. Beginning at 2 mo of age, 4-day-cycling, virgin rats were divided into two groups. In one group, 3 Silastic capsules containing crystalline P were inserted s.c. into each rat while rats in another group each received 1 empty capsule. After 2 wk, the capsules were removed for 2 wk. Thereafter, implantation and removal of capsules was repeated 5 additional times. Rats receiving P capsules became acyclic 3-4 days after exposure to P and resumed cyclicity 4-7 days after removal of P-capsules. One month after the last series of capsules was removed (rats approximately 8-mo-old), rats exhibiting consecutive 4-day cycles were inserted with indwelling atrial cannulae and bled at 4-h intervals from 1400 h on proestrus (Pr) to 1000 h on estrus (E). At 1600 h E, rats were killed and trunk blood was collected. For comparison, a group of 3-mo-old (young) rats was bled on Pr and E. In 8-mo-old rats that received empty capsules, 27% exhibited 4-day cycles compared to 66% of the young rats. However, in contrast to rats that received empty capsules, 63.1% of P-treated rats exhibited 4-day cycles. Surges of preovulatory luteinizing hormone (LH) and follicle-stimulating hormone (FSH) surges were attenuated in 8-mo-old rats given empty capsules compared to young rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Luteolytic effect of prolactin is dependent on the degree of differentiation of luteal cells in the rat

We studied the morphological and quantitative changes in cyclic corpora lutea (CCL) and in CL of pregnancy (CLP) during structural luteolysis. Elimination of CCL takes several cycles, and cell death occurs as successive apoptotic bursts, from 2100 h in proestrus to 1300 h in estrus. Each apoptotic burst determined a 60% decrease in the CL volume and an 80% decrease in the number of steroidogenic cells (SC). All these changes were inhibited by blocking the preovulatory prolactin (PRL) surge with bromocryptine (CB154). Neither apoptotic cells nor changes in the number of SC were found in regressing CLP from Day 21 of pregnancy to Day 2 postpartum, although there was a 50% decrease in the CLP volume and a 30% decrease in the mean cross-sectional area of SC. Treatment with CB154 on the day of parturition did not modify these regressive changes. On Day 5 postpartum, the volume of the CLP and the number of SC were equivalent in lactating rats (showing high PRL concentrations induced by pup suckling) and nonlactating noncycling rats (in which cyclicity and, therefore PRL surges, were blocked by treatment with LHRH antagonist). However, on Day 10 postpartum, the CLP volume and the number of SC were significantly decreased in lactating rats, and apoptotic cells were frequent. In postpartum cycling rats, the CLP did not show apoptotic cells on the day of the second postpartum estrus (on Day 5 postpartum), whereas on the day of the third postpartum estrus (on Day 9 postpartum), apoptotic cells were abundant. These results indicate that PRL does not induce apoptosis in the CLP before Day 5 postpartum and strongly suggest that the proapoptotic effect of PRL is dependent on the degree of differentiation of luteal cells.     

Collagen concentrations in dissected tissue compartments of rat uterus on days 6, 7 and 8 of pregnancy.

Implantation and non-implantation sites were dissected into myometrial and stromal components; a decidual/embryonic region was obtained on Days 7 and 8 of pregnancy. The concentration of collagen (as a percentage of the dry weight of tissue), measured by hydroxyproline analysis, was significantly lower in the implantation regions than in the non-implant regions in all areas studied. The concentrations in the antimesometrial myometrium and stroma of the implantation region remained the same over the days studied. In contrast, the mesometrial collagen concentration in the implantation region declined from Day 6 to Day 8 of pregnancy. Collagen concentration was low within the decidual/embryonic tissue on Days 7 and 8 of pregnancy. Remodelling of collagen within the embryonic area appears to be an important feature of the uterine response to implantation in rats.     

Selected contribution: chronic intermittent hypoxia enhances respiratory long-term facilitation in geriatric female rats.

Age and the estrus cycle affect time-dependent respiratory responses to episodic hypoxia in female rats. Respiratory long-term facilitation (LTF) is enhanced in middle-aged vs. young female rats (72). We tested the hypothesis that phrenic and hypoglossal (XII) LTF are diminished in acyclic geriatric rats when fluctuating sex hormone levels no longer establish conditions that enhance LTF. Chronic intermittent hypoxia (CIH) enhances LTF (41); thus we further predicted that CIH would restore LTF in geriatric female rats. LTF was measured in young (3-4 mo) and geriatric (20-22 mo) female Sasco Sprague-Dawley rats and in a group of geriatric rats exposed to 1 wk of nocturnal CIH (11 vs. 21% O2 at 5-min intervals, 12 h/night). In anesthetized, paralyzed, vagotomized, and ventilated rats, time-dependent hypoxic phrenic and XII responses were assessed. The short-term hypoxic response was measured during the first of three 5-min episodes of isocapnic hypoxia (arterial Po2 35-45 Torr). LTF was assessed 15, 30, and 60 min postepisodic hypoxia. Phrenic and XII short-term hypoxic response was not different among groups, regardless of CIH treatment (P > 0.05). LTF in geriatric female rats was smaller than previously reported for middle-aged rats but comparable to that in young female rats. CIH augmented phrenic and XII LTF to levels similar to those of middle-aged female rats without CIH (P < 0.05). The magnitude of phrenic and XII LTF in all groups was inversely related to the ratio of progesterone to estradiol serum levels (P < 0.05). Thus CIH and sex hormones influence the magnitude of LTF in geriatric female rats.     

Growth hormone is secreted by ectopic pituitary grafts and stimulates maternal behavior in rats

The onset of maternal behavior at parturition in rats is hormonally regulated. Recently, we reported that treatment of behaviorally inexperienced, hypophysectomized (hypox), ovariectomized (ovx) rats with a sequential steroid treatment of progesterone (P) and estradiol (E2), and either ectopic anterior pituitary grafts or prolactin (PRL), stimulated maternal responsiveness toward foster young. That growth hormone (GH) has a number of PRL-like activities led us to ask whether the actions of PRL on maternal behavior were specific to PRL or might be shared by other PRL-like protein hormone, i.e., GH. In Experiment 1 we quantified plasma concentrations of GH and PRL by RIA in groups of hypox female rats that were ovariectomized and treated with a combination of ectopic pituitary grafts (Days 1-23) and Silastic capsules filled with P (Days 1-11) and E2 (Days 11-23). Blood samples were collected from Days 1 to 23 of treatment. Both plasma PRL and GH levels increased after grafting, initially rising 10- to 60-fold by Day 4 and gradually declining throughout the remainder of the 23-day sampling period. Throughout the 3-week period after grafting plasma GH levels were as high or higher than those of PRL. In Experiment 2 the behavioral effects of exogenously administered ovine (o)-GH were measured in groups of hypox, ovx rats that were treated with P and E2 as in Experiment 1. Experimental rats were injected twice daily with 0.25 mg oGH beginning on Day 1. Testing for maternal behavior toward foster young was conducted daily from Day 12 to Day 22. In steroid-treated rats, GH treatment stimulated a more rapid onset of maternal behavior (latencies of 3 vs greater than 10 days for vehicle-injected controls). These data indicate that GH, like PRL, is secreted by ectopic pituitary grafts and is capable of stimulating maternal behavior.     

Effect of exogenous progesterone on pregnancy rates after surgical embryo transfer in mares

A completely randomized experimental design was used to investigate the effect of supplemental progesterone on pregnancy rates of recipient mares. Every other recipient mare received daily 200 mg progesterone in oil beginning the day of surgical embryo transfer and lasting until either Day 120 of pregnancy or until pregnancy failure was confirmed by ultrasound. Progesterone supplementation did not affect pregnancy rate (P > 0.05). Overall, embryos that did not result in pregnancy were of greater mean diameter than embryos that resulted in pregnancy (P < 0.05). Pregnancy rates tended (P < 0.1) to be greater in recipients that were detected to be ovulating the same day or prior to that of the donor and that had been supplemented with progesterone (75 %) as opposed to untreated control mares of the same synchrony group (40 %). Progesterone supplementation did not affect the incidence of embryonic loss; however, there was a slightly higher loss of pregnancies between Day 15 and 30 in treated versus untreated recipients. There was no effect (P > 0.05) of treatment on pregnancy rate for embryos recovered from fertile versus subfertile donor mares. However, overall, there tended (P < 0.1) to be fewer pregnancies with embryos recovered from subfertile (50 %) as compared to fertile donors (75 %). It was concluded that supplemental progesterone at the dosage and frequency described was not beneficial in improving pregnancy rates in cyclic recipient mares after surgical embryo transfer.     

Ovarian and PGF2α responses to stimulation of endogenous PRL pulses during the estrous cycle in mares

The effects of a PRL-stimulating substance (sulpiride) on PRL and PGF2α secretion and on luteal and ovarian follicular dynamics were studied during the estrous cycle in mares. A control group (n = 9) and a sulpiride group (Sp; n = 10) were used. Sulpiride (25 mg) was given every 8 h from Day 13 postovulation to the next ovulation. Repeated sulpiride treatment did not appear to maintain PRL concentrations at 12-h intervals beyond Day 14. Therefore, the hypothesis that a long-term increase in PRL altered luteal and follicular end points was not testable. Hourly samples were collected from the hour of a treatment (Hour 0) to Hour 8 on Day 14. Concentrations of PRL increased to maximum at Hour 4 in the Sp group. The PRL pulses were more prominent (P < 0.008) in the sulpiride group (peak, 19.4 ± 1.9 ng/mL; mean ± SEM) than in the controls (11.5 ± 1.8 ng/mL). Concentrations of a metabolite of PGF2α (PGFM), number, and characteristics of PGFM pulses, and concentrations of progesterone during Hours 0 to 8 were not affected by the increased PRL. A novel observation was that the peak of a PRL pulse occurred at the same hour or 1 h later than the peak of a PGFM pulse in 8 of 8 PGFM pulses in the controls and in 6 of 10 pulses in the Sp group (P < 0.04), indicating that sulpiride interfered with the synchrony between PGFM and PRL pulses. The hypothesis that sulpiride treatment during the equine estrous cycle increases concentrations of PRL and the prominence of PRL pulses was supported.     

Dissociation between increased growth hormone and prolactin secretion during the morning hours of early pregnancy in the rat

We investigated whether serum growth hormone (GH) concentration changes in association with the rise in serum prolactin (PRL) concentration known to occur during the early morning hours in the pregnant rat. Animals were kept in a room with the lights on from 0500 to 1900 hours (hr) daily and decapitated for the collection of trunk blood at 2200 or 2400 hr on Day 6 of pregnancy or at 0200, 0400, 0800 or 1000 hr on Day 6 of pregnancy. Serum GH concentration rose more than 4-fold from low levels at 2200 and 2400 hr to higher levels at 0400 and 0800 hr and then declined by 1000 hr. Serum prolactin (PRL) concentration followed a similar pattern except that it returned to low levels earlier, by 0800 hr. Serum luteinizing hormone, follicle-stimulating hormone and thyroid-stimulating hormone concentrations showed no significant changes. Serum GH levels at 0800 hr in pregnant rats were higher than those observed in cyclic rats (13 time periods sampled). The results demonstrate that serum GH concentration is elevated during a circumscribed period in the 6- to 7-day pregnant rat. The time of onset of the rise is similar to that for serum PRL but the elevation in GH levels persists longer than that for PRL.     

Studies on the involvement of prostaglandins in implantation in the rat

Studies of prostaglandin (PG) production by uterine homogenates of rats in early pseudopregnancy and pregnancy showed that production of 6-oxo-PGF-1 alpha, PGF-2 alpha and PGE-2 peaked on Day 5 of pseudopregnancy whereas only 6-oxo-PGF-1 alpha and PGE-2 peaked on Day 5 of pregnancy, the day of implantation. 6-Oxo-PGF-1 alpha was the major product in both reproductive states. Indomethacin treatment of rats during early pregnancy caused a delay in implantation, a significant reduction in uterine weight, and a much reduced number or absence of implanted blastocysts in the uterus on Day 9. Plasma progesterone levels were also significantly lower in indomethacin-treated, pregnant rats. These findings support roles for prostaglandins in implantation, and in fetal development.     

Age-related alterations in pulsatile luteinizing hormone release: effects of long-term ovariectomy, repeated pregnancies and naloxone

Aging of the female reproductive system may be regulated by changes at the hypothalamic, pituitary, and ovarian levels. Long-term ovariectomy (LT-OVX) and/or multiple pregnancies delay age-related deterioration of several parameters of reproductive potential in rodents. We tested whether long-term suppression of cyclic ovarian hormone release that is normally associated with the 4- to 5-day estrous cycle decelerates age-related decreases in the frequency of luteinizing hormone (LH) pulses to assess whether hormonal milieu influences the rate of aging of the pulse generator. We determined the percentage of rats exhibiting pulsatile LH secretion, mean LH levels, and amplitude and frequency of LH pulses in seven groups of ovariectomized (OVX) rats. Young (3-4 mo), middle-aged (8-10 mo), and old (18-22 mo) virgin rats, ovariectomized 4 wk (4WK-OVX) prior to experimentation, were used to determine the effect of age. The effect of long-term ovarian hormone deprivation was tested by ovariectomizing rats at 2-3 mo of age and using them when they were middle-aged (8-10 months) or old (18-22 mo). The effect of deprivation of cyclic increases in ovarian hormones associated with repeated estrous cycles was tested by using retired breeder (RB) rats that had been ovariectomized 4 wk prior to experimentation. Each rat was implanted with a right atrial cannula and bled the next day at 10-min intervals for 3 h.(ABSTRACT TRUNCATED AT 250 WORDS)