Vaginal Estrus Research Articles

Persistent vaginal estrus and serum hormones after chlordecone (Kepone) treatment of adult female rats

The effects of chlordecone on vaginal estrus and neuroendocrine responses were examined in adult ovariectomized and intact females. Persistent vaginal estrus was seen in females given 50 mg/kg or more of chlordecone. The development of vaginal estrus was similar to that seen in ovariectomized females after treatment with estrogen. Since chlordecone is known to have estrogen-like effects on the reproductive system, the persistent vaginal estrus probably results from this estrogen-like action and chlordecone's long half-life in the organism. Neuroendocrine effects of chlordecone also resembled, to some degree, estrogen's effects on pituitary secretions. Chlordecone increased serum prolactin and decreased serum luteinizing hormone (LH) in ovariectomized females 30 to 36 hr after a single exposure to 50 mg/kg of the pesticide. Basal LH levels were not altered in intact females, but the proestrous LH surge was suppressed by 36 hr after treatment. Both basal and proestrous levels of prolactin were suppressed. Unlike the effects of estrogen, serum follicle stimulating hormone was not altered by chlordecone. These results indicate an effect on the hypothalamic pituitary axis by chlordecone treatment and offer a possible explanation for the reduced fertility seen in adult females after chlordecone exposure. However, blockage of the proestrous LH surge was not obligatory for the appearance of vaginal estrus. Although chlordecone produced peripheral changes in the vaginal smear pattern as well as neuroendocrine alterations, the peripheral changes were not always indicative of the neuroendocrine events.

Endocrine status versus chronologic age as predictors of altered luteinizing hormone secretion in the "aging" rat.

LH release in response to GnRH injected at 1400 h was measured in young (3-4 months), middle-aged (10-11 months), and old (19-20 months) female rats. Data were compared when animals were grouped by chronological age or according to their vaginal smear pattern 3-4 weeks before treatment, i.e. regular 4-day cycles, constant vaginal cornification (CVC), or persistently leukocytic smears (PL). Compared to young, regularly cycling females (injected on vaginal estrus or diestrus II), the amount of LH released by all age groups with CVC or PL smears was significantly diminished. However, regardless of age, the amount of LH released by CVC females was similar for each dose of GnRH. Similarly, there was no difference in the amount of LH released by the young, middle-aged, and old PL females at each dose of GnRH. Finally, the amount of LH released by the CVC females was uniformly higher than the amount of LH released by age-matched PL females. In contrast, comparison of LH release after GnRH injection in young and middle-aged rats with regular 4-day vaginal cycles showed that the middle-aged rats released significantly less LH on proestrus. These data suggest that changes in the ability of the pituitary to release LH in the older noncycling female rat occurs as a consequence of the altered endocrine status in the animal and not as a result of the chronological age per se. Changes in the ability of the pituitary of the middle-aged, regularly cycling female rat to release LH in response to GnRH may contribute to the age-related disruption of regular ovarian cycling.

Localization of central nervous system structures mediating extracellular thirst in the female rat.

Water intake elicited by microinjection of the hormone angiotensin-II into the preoptic region of cyclic female rats was significantly less on days of vaginal oestrus than at dioestrus or metoestrus, whereas the drinking of 2.7% NaCl solution, to which rats also had access, did not vary with the cycle. Administration of the same dose of angiotensin-II to the subfornical organ and the lateral cerebral ventricles induced drinking at all stages of the oestrous cycle, but the volumes of water or 2.7% NaCl ingested did not vary with the cycle. Water intake after subcutaneous injection of isoprenaline, a beta-adrenergic agonist which causes increased angiotensin biosynthesis, varied cyclically with the stage of the oestrous cycle. On the other hand, water and 2.7% NaCl intakes induced by intraperitoneal injection of hypertonic NaCl (a cellular stimulus of thirst) or by 24-h water deprivation (which dehydrates both the extracellular and cellular body fluid compartments) did not differ significantly at the various stages of the oestrous cycle. The finding that fluctuations in angiotensin- and isoprenaline-induced water intake parallel the changes in spontaneous 24-h drinking suggests that the preoptic region may play an important role in the maintenance of extracellular fluid balance in synchrony with the oestrous cycle.

Influence of continuous illumination on estrous cycle of rats: time course of changes in levels of gonadotropins and ovarian steroids until occurrence of persistent estrus.

Plasma concentrations of LH, FSH, 17 beta-estradiol, estrone and progesterone were determined chronologically by radioimmunoassays in two groups of adult female rats exposed to continuous illumination (LL). Group 1 rats showing vaginal estrous cycles were sacrificed at 3- to 6-hour intervals during late proestrus through early estrus of the first 5 cycles after exposure to LL. Group 2 animals which displayed persistent vaginal estrus in an early period of exposure to LL were killed on the 2nd, 3rd, 4th, 5th and 7th days of vaginal estrus. In Group 1 rats, surges of the hormones, except estrone, took place in all the 5 cycles. The occurrence of peak hormone levels in each cycle was invariably delayed after transfer of animals to LL. According to regression analyses, the lengths of secretion cycles of LH, FSH, 17 beta-estradiol and progesterone in rats under LL were 100.89, 100.46, 101.14 and 101.06 h, respectively. Elevation of 17 beta-estradiol levels was observed prior to the LH surge, and peaks of progesterone and FSH occurred following it. However, the secretion patterns of these hormones appear to be disrupted with length of exposure to LL. In group 2 rats, the mean concentration of LH during persistent estrus was approximately similar to that on the morning of the days of proestrus of the 4-day cycles of rats placed under an alternating 12-hour light-dark regimen (LD), whereas the mean FSH concentration was continuously low. While the concentrations of 17 beta-estradiol and estrone in persistent-estrous rats were elevated, progesterone levels remained low.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of period of grouping of donors and duration of stimulus exposure on delay of puberty in female mice by a urinary chemosignal from grouped females.

Females housed at a density of 8 mice/cage had to be grouped for a minimum of about 10 days before their urine was capable of producing delays for first vaginal oestrus in test females comparable to the delays occasioned by treatment with urine from females grouped for 30 days or longer. Young test females had to receive a minimum daily exposure of 1-2 h to the chemosignal to produce the complete delay of puberty.

Mice selected for age of puberty: reverse selection and reproductive characteristics.

Previous investigations have hypothesized a link between regulation of population size in various rodent species and changes in allele frequencies for certain loci that exert their effects on particular behaviors or processes related to reproduction. Drickamer (1981a) has shown that age of first vaginal estrus can be shifted by artificial selection and that there is a relatively high heritability for this trait in laboratory Mus. This paper reports on two related experiments, one a test of reverse selection on strains of mice previously selected for early and late first vaginal estrus, and the other a compilation of data for a variety of traits related to reproduction for the original base stock and four artificially selected stocks. The original selection for early and late onset of puberty did not result in fixation of the trait-enough residual variation remained so that in eight generations of selection it was possible to significantly reverse the timing of first estrus. Traits related to reproduction including litter size, pup weight, survival of pups to 21 days, weight at 21 days, fertility and birth intervals all were not affected by the selection process across all five stocks tested. These results are discussed with regard to changes in puberty and generation time in Mus as a factor in population regulation.

Male acceleration of puberty in female mice (Mus musculus).

Nine experiments were performed to investigate various aspects of the acceleration of puberty in female house mice produced by the presence of a male mouse or urine from males. The findings include the following: (a) Grouping males has no effect on the urinary chemosignal that accelerates puberty except that (b) urine from dominant males produces greater acceleration than urine from subordinates. (c) Young female mice must be exposed to the male urine for at least 2-3 hr/day or to the presence of a male for 1 hr/day to produce acceleration of first vaginal estrus. (d) Females are accelerated to the same extent in attaining puberty whether treated with urine from the same male or a different male each day. (e) Urine from the father or a full brother, or the presence of those close relatives, exerts no differential acceleratory or retarding effect on puberty when compared with urine from or the presence of unrelated males. (f) Excreted or bladder urine from adrenalectomized males accelerates puberty to the same extent as urine from intact males, but (g) the presence of an adrenalectomized male does not produce the same degree of acceleration that occurs when an intact male is present. (h) Behavioral observations indicate that adrenalectomized males pursue young females less and attempt fewer mounts during a brief test period. Together, these findings have some important consequences with respect to our understanding of both the mechanisms of acceleration of puberty in the house mouse and the population and reproductive biology of these mice.

Acceleration and delay of sexual maturation in female mice via chemosignals: circadian rhythm effects.

Two experiments tested whether the male urinary chemosignal that accelerates puberty in female mice or the urinary chemosignal from grouped females that delays puberty are affected by circadian rhythms. The experiments also tested whether there is a circadian component for the response system(s) of the young recipient female mice for the onset of first vaginal estrus. Male urine collected at 0600 h was more effective in inducing earlier maturation than urine collected at 0000, 1200 or 1800 h. Urine from grouped females collected at all four times produced significant delays in first estrus, but urine collected at 0000 h produced longer delays than urine from 0600, 1200 or 1800 h. For male urine, application at 0600 h produced significant acceleration relative to urine treatment at 0000, 1200 or 1800 h. No differences were recorded in age of puberty in females treated with urine from grouped females when urine was applied at the four different time points. Possible interpretations of these results involve circadian variations for various hormones and related physiological processes in both donor and recipient mice.

Role of the preimplantation embryo in the timing of LH-dependent progesterone secretion from the rat corpus luteum.

AbstractThe effect of the progestational uterus and preimplantation embryo on the time of appearance of LH-dependent progesterone secretion from pregnant and pseudopregnant (PSP) rat corpora lutea (CL) was studied. Two groups of experiments were performed: (1) pregnant and PSP rats were hysterectomized between Days 3 and 5 (Day 1 = vaginal estrus) and subsequently monitored for changes in serum progesterone levels following an injection of LH antiserum (LHAS) or normal horse serum (NHS) vehicle on Day 9 and, (2) Day 4 embryos were transferred to Day 3 PSP uteri; each rat was subsequently hysterectomized on Day 4 of PSP and treated with LHAS or NHS on Day 9. Progesterone levels were monitored as an index of luteal vitality. Progesterone secretion was not altered by NHS treatment in any group. LHAS treatment did not induce luteolysis in Day 3 pregnant rats or in PSP rats hysterectomized on Days 3 or 4. However, in rats hysterectomized on Day 4 or 5 of pregnancy, or hysterectomized on Day 5 of PSP, luteolysi...

Neonatal exposure to zearalenone causes persistent anovulatory estrus in the rat.

The effect of neonatal administration of zearalenone on the female reproductive system was studied in the rat. A single subcutaneous injection of 1.0 mg zearalenone to 3- or 5-day-old rats caused persistent vaginal estrus in adulthood. Ovaries in these animals contained many large follicles but no newly formed corpora lutea. The same effects were observed in rats which had received 100 micrograms estradiol-17 beta in the neonatal period. Most rats which had received 100 micrograms zearalenone or 10 micrograms estradiol-17 beta showed regular 4-day estrous cycles and had newly formed corpora lutea in their ovaries. These results demonstrate that neonatal exposure to zearalenone produced persistent anovulatory estrus in the rat, the potency being about one tenth that of estradiol-17 beta.

Acceleration and delay of first vaginal oestrus in female mice by urinary chemosignals: Dose levels and mixing urine treatment sources

The effects of varying dose levels and mixing of urine from various types of donor mice on the age of sexual maturation in female mice were tested. Over the range from 0.001 ml/day to 0.01 ml/day, there was no difference in the effectiveness of male urine in producing acceleration of puberty, nor was there any difference over the same dose range for urine from grouped females bringing about a delay of puberty. Urine from pregnant and lactating females brought about earlier puberty when applied in the higher dose amounts but was not effective in altering the age of first oestrus relative to untreated controls at lower doses. These findings concerning dose levels are important for a full understanding of the behavioural consequences of urinary chemosignals. When urine from different sources was mixed, all treatments which involved urine from grouped females produced delays in first oestrus. The second finding has important consequences for a feedback model for population regulation in house mice involving urinary chemosignals that accelerate or delay sexual maturation and thus shorten or lengthen generation time by affecting reproductive behaviour.

Analysis of the estrous cycle of the laboratory-housed Senegal galago (Galago senegalensis senegalensis): natural and induced cycles.

The natural estrous cycle of captive Senegal galagos was analyzed from daily records of 11 cycling females for 18 months, and induction of vaginal estrus and ovulation by gonadotropins and estrogen were examined in 9 females. No seasonal trend in cycling was indicated, as at least 5 of the 11 cycling females exhibited vaginal estrus during each month. Cycle lengths and duration of estrus were consistent for each female but varied significantly among females. Individuals' average cycle lengths ranged from 29.2 +/- 0.8 to 39.3 +/- 3.4 days, and duration of estrus from 4.8 +/- 0.2 to 6.7 +/- 0.4 days. Vaginal estrus was induced by PMSG and PMSG-HCG combinations, and by estradiol. The gonadotropins also induced growth and ovulation of more than one follicle.

Responses to copulatory stimulation in neonatally androgenized female rats.

A series of experiments evaluated the extent to which copulatory stimulation could ameliorate the anestrus and sterility exhibited by neonatally androgenized female rats. The age at which animals began to exhibit persistent vaginal estrus and the degree of sexual receptivity exhibited under several testing paradigms were found to be inversely related to the dose of testosterone propionate (TP) injected neonatally. With increasing numbers of mounts received, both the number of androgenized animals exhibiting sexual receptivity and the quality of the estrous behavior exhibited tended to increase. The extent to which copulatory stimulation modified receptivity varied with the dose of TP injected neonatally and the condition of testing. Animals injected with high doses of TP (500 microgram) usually showed little or no receptive behavior even in the most extensive behavioral tests. However, under some testing conditions animals receiving 50 micrograms of TP neonatally, while showing little or no receptivity during initial mounts, showed increased receptivity as behavioral tests were extended. Following matings that included one to five ejaculations, only control animals were observed to become pregnant. However, when androgenized females cohabited with males for an extended period, animals that had neonatally received .5 microgram of TP, but not higher doses, did become pregnant. It is concluded that the capacity of systems mediating reproductive physiology and behavior to be facilitated by stimuli associated with males and that mating is a characteristic of the female rat which can be manipulated by injection of hormones during the neonatal period.

Acceleration and delay of sexual maturation in female house mice previously selected for early and late first vaginal oestrus.

Female mice previously selected for early and late sexual maturation were tested to determine whether they retained flexibility in age of puberty in response to pheromonal and social cues. First vaginal oestrus in fst-maturing females could be delayed but not accelerated by social cues. Conversely, puberty in slow-maturing females could be accelerated in their sexual development, but not delayed. Two additional experiments demonstrated that mice from the fast- and slow-maturing lines retained the capacity to accelerate and delay puberty via pheromonal and social cues.

Bromocryptine treatment and puberty attainment in the female rat

The influence of bromocryptine treatment on the timing of vaginal patency and 1st oestrus in female rats was studied. No significant influence of bromocryptine on these parameters was noted, and it is concluded that suppression of prolactin secretion has no effect on puberty attainment.

Plasma prolactin and progesterone responses to mating are altered in ages rats.

The effects of varying amounts of copulatory stimulation on patterns of plasma concentrations of prolactin and progesterone were evaluated in 3- and 12-month-old female rats. The 12-month-old group included rats which still exhibited oestrous cycles and rats in persistent vaginal oestrus (PVO). The extent of copulatory stimulation was defined by the number of intromissions received during mating: less than or equal to 5, 15 or greater than 50. Blood samples were drawn over the 8 days after mating through a cannula inserted into the right external jugular vein. Plasma from the samples was assayed for prolactin and progesterone. In aged but still cyclic rats, pregnancy rates were positively correlated with the number of intromissions received during mating. Only one rat in PVO became pregnant. All animals which became pregnant and rats in PVO which, after mating, exhibited a disruption of the pattern of PVO, showed the nocturnal surge of plasma prolactin characteristic of pregnant and pseudopregnant rats. While these surges persisted until day 8 after mating in pregnant animals, they were absent by this time in the rats in PVO. Prolactin surges were present in some but not all of the aged rats which did not become pregnant. Progesterone concentrations were raised in all pregnant animals except the one pregnant rat in PVO and, while not related to the number of intromissions, concentrations were higher 8 days after mating in young compared with those in aged pregnant rats. Plasma progesterone was low in rats in PVO regardless of disruption of the pattern of PVO. We have concluded that the failure of limited copulatory stimulation to induce pregnancy in older rats results, at least in part, from its failure to initiate nocturnal prolactin surges. Nevertheless, our data suggest that matings which are not experimentally limited should provide ample stimulation to establish such surges. Although reduced plasma concentrations of prolactin and progesterone at pro-oestrus and reduced plasma progesterone through part of gestation may contribute to decreasing fertility in aged rats, other unidentified factors appear to be involved in mediating the capacity of extensive copulatory stimulation to induce pregnancy in these animals.

The relationship of the oestrogen and progestin receptors in the abnormal uterus of the adult anovulatory rat. Effects of neonatal treatment with testosterone propionate or clomiphene citrate.

The neonatal administration of testosterone propionate to Wistar rats resulted in anovulatory adults in persistent vaginal oestrus. Clomiphene citrate had a similar effect. In both groups of adults, hyperplasia of the uterine epithelium and occasional metaplasia was observed. The uterine nuclear and cytosol oestrogen and progestin receptors of these anovulatory rats were found to have affinities for their respective ligands similar to those of normal females. The nuclear oestrogen receptor comprised occupied and unoccupied components, as in normal females. The content of the nuclear oestrogen receptor was comparable with that of females in the late dioestrous or pro-oestrous phase. This content was higher in the clomiphene-treated group. Despite the relatively high nuclear oestrogen receptor content the content of progestin receptors, a putative index of the oestrogenic response, was lower in the treated rats than in normal adult females throughout the cycle. Administration of oestradiol to both treatment groups resulted in depletion of cytosol oestrogen receptor content 1 h later, which, however, was not reflected by an increase in the content of nuclear oestrogen receptors. There was no measurable increase in progesterone receptor content in treated rats after daily administration of oestrogen (5 microgram/rat) for 3 days. These changes in sex-hormone-receptor interactions involving an impairment of the normal oestrogenic response may be associated with the abnormal differentiation of the uterus in these sterile, anovulatory animals.

Selection for age of sexual maturation in mice and the consequences for population regulation

Laboratory stocks of Mus musculus were selected for early and late first vaginal estrus for six generations. Selection resulted in two slow lines which mature at 47–48 days of age and two fast lines which mature at 27–28 days of age; control stocks attain first estrus at 34–36 days of age. Estimates of realized heritabilities were .58 and .32 for the two fast-selected lines and .49 and .55 for the two slow-selected lines. These data support the hypothesis that short-term selection for age of puberty could affect population growth via effects on generation time. Correlative data on body weights at various ages and at vaginal introitus and first estrus support the conclusion that there are largely separate programs for sexual and morphological development in these mice.

Sexual behavior and some of its physiological consequences in persistently estrous aged female rats

Sexual behavior and some of its consequences were assessed in female rats which, with advancing age, had come to exhibit persistent vaginal estrus (PVE). Sexual receptivity, defined by the animal’s readiness to exhibit lordosis when mounted, was comparable across all ages evaluated. However, sexual proceptivity, defined by measures indicative of the female’s seeking mating opportunities, was determined to be much suppressed in 18 to 20 month old PVE females compared to either younger cyclic females or 12 to 15 month old PVE females. Mating disrupted the PVE pattern. The length of time animals remained out of estrus was positively correlated with the number of intromissions achieved by the male. However, pregnancy was not observed in any of the PVE females and examination of their ovaries and the responses of their uteri to traumatization provided no evidence of progestational responses in these animals. The behavioral data indicate that with continued exposure to the hormonal conditions of PVE there is a suppression of systems mediating the proceptive components of sexual behavior in female rats. It is suggested that changes in the concentrations of pituitary and/or ovarian hormones reported to occur as PVE rats continue to age may account for these changes in behavior.

LHRH-induced LH and FSH responses in the aged female rat.

LHRH-induced LH and FSH concentrations were measured in 8 to 12-month-old rats which had just begun to exhibit constant vaginal estrus (CE) or prolonged vaginal diestrus (PD) and in young rats on the day of proestrus (PE). All animals were anesthetized with sodium pentobarbital (31 mg/kg). They received (1) i.v. infusion of LHRH (Beckman 100 ng/ml at a rate of 0.5 ml/hr) for 3 hrs or (2) 2 i.v. injections of LHRH (50 ng/100 g body wt) spaced 120 min apart. LHRH stimulation resulted in a comparable gonadotropin response in young rats and old CE rats; however, old PD rats exhibited a markedly attenuated LH and FSH response to LHRH infusion. These data suggest that pituitary responsiveness to LHRH does not change in 8 to 12-month-old CE rats and therefore does not play a major role in the transition to acyclicity. In contrast, pituitary responsiveness is decreased in old PD rats early during the aging process and therefore may be an important factor in the transition to their acyclic vaginal smear pattern.