Patterns of apoptosis in the corpora lutea of the rat during the oestrous cycle, pregnancy and in vitro culture.

Apoptosis is associated with regression of corpora lutea (CL) in a number of species. The present work compared apoptotic rates, assessed by low molecular weight DNA labelling, in rat CL of the oestrous cycle, pregnancy, the immediate post-partum period, and in vitro culture. Apoptosis was significantly related to cycle phase with peak activity at oestrus. This pattern was similar in CL formed from the most recent ovulation and from the two previous generations. Apoptosis was evident during pregnancy, albeit at low rates. It declined on the day of parturition and increased on the following day. Apoptosis was greatly increased in cultured CL to reach 20-fold higher levels than those achieved during the oestrous cycle or pregnancy. Collectively, these results suggest that apoptosis has lesser significance in rat CL functional regression than in other species with more precipitate structural changes. However, rat CL clearly retain the potential for high rates of apoptosis and so present a useful model for examining molecular mechanisms of apoptotic cell death.

Incidence and duration of romantic attraction in students progressing from secondary to tertiary education.

There is increasing interest in the nature and biological significance of romantic love but few quantitative data are available for testing specific hypotheses. This paper describes the use of a survey instrument to assess incidence and duration of romantic attractions over a 2-year period amongst students (121 male; 162 female) progressing from school to university education. The results for males and females were similar and schooling single-sex or co-educational--had little effect. Students averaged 1.45 romantic episodes per year and 93% of students reported at least one episode over the survey period. Duration of attraction was around 9 weeks if never reciprocated and around 12 weeks if reciprocated. There was seasonal variation of onset of episodes with peak incidence over the summer or early autumn seasons. Collectively the results accord with the view that frequent, short-duration romantic episodes could have a role in selection of appropriate long-term reproductive partnerships.

Psychosocial stress and the menstrual cycle.

The relationship between mood states, urinary stress hormone output (adrenaline, noradrenaline and cortisol) and adequacy of the menstrual cycle was examined in 120 recorded non-conception cycles from 34 women. It was hypothesized that women with higher stress levels would be more likely to experience abnormal cycles and that within women higher stress levels would positively relate to follicular phase length and inversely relate to luteal phase length. There was a non-significant trend for women to report higher stress levels during oligomenorrhoeic and unclear cycles compared with normal cycles. Analysis of covariance indicated that there was no consistent relationship between the measures of stress used here and follicular or luteal phase length within women. There was also no consistent pattern of relationship between reported mood states and stress hormone excretion within women. Further research is warranted to understand the role of stress and subtle menstrual cycle abnormalities in female fertility.

PIP: These analyses were concerned with the effect of psychosocial stress on subtle menstrual cycle abnormalities, such as anovulatory cycles, delayed ovulation and luteal phase defects. The relationship between mood states, urinary stress hormone output (adrenaline, noradrenaline and cortisol) and adequacy of the menstrual cycle was examined in 120 recorded non-conception cycles of 34 women. It was assumed that if stress contributed to cycle abnormalities, stress levels would be higher in abnormal cycles than in normal ones. The two-way variance analysis showed no statistically significant difference among normal cycles, short luteal phase cycles and combined oligomenorrheic cycles; it did not show showed clear pattern cycles for any of the urinary hormone excretion rates. Short luteal phase length is associated with decreased progesterone secretion, which has important implications for female fertility. Overall, though, the initial hypothesis that abnormal cycles would relate to higher levels of stress for individual women was not supported.

Psychosocial stress and treatment outcome following assisted reproductive technology.

This study investigated the association between psychosocial stress and outcome of in-vitro fertilization and gamete intra-Fallopian transfer treatment. Ninety women, enrolled for treatment at a private infertility clinic, completed two self-administered psychometric tests (Bi-polar Profile of Mood States, POMS; and State-Trait Anxiety Inventory, STAI) and a questionnaire to ascertain demographic and lifestyle characteristics before the start of treatment. Approximately 12 months later an outcome measure was determined for each participant in terms of whether she was pregnant or not pregnant and the number of treatment cycles undertaken to achieve clinical pregnancy. The women's scores on the psychological tests were similar to published normative scores. On univariate analysis, history of a previous pregnancy was positively related to the probability of pregnancy and full-time employment, a more 'hostile' mood state and higher trait anxiety were associated with a lower cumulative pregnancy rate. A Cox multiple regression model found previous pregnancy history, trait anxiety, and the POMS agreeable-hostile and elated-depressed scales to be the most important lifestyle and stress variables predictive of pregnancy. The results emphasize the importance of psychosocial stress in treatment outcome but indicate that the relationships are complex. Further studies are required to validate whether these findings can be generalized to other populations.

Embryo survival, and fetal and placental growth following elevation of maternal estradiol blood concentrations in the rat.

High doses of estrogens cause embryonic mortality, and fetal and placental growth retardation in rats. This study addresses the physiological relevance of such findings. Estradiol benzoate (EB), by s.c. injection, or estradiol-17beta (E2), delivered by a miniosmotic pump, raised maternal E2 concentrations from only slightly above control values to 5-fold. EB (1 microgram/day) over Days 6-13, 8-13, and 11-13, and continuous infusion of E2 (15 ng/h; Days 10-13) reduced fetal survival to 0%, 0%, 22%, and 75%, respectively. Single injections of EB showed that its lethal effect declined rapidly over Days 9 (44% survival) to 13 (90% survival). Embryos died within 48 h, but death was not due to luteal failure since progesterone levels were maintained and progesterone administered with EB did not reduce mortality. Administration of EB at 1 microgram/day (Days 14-21) or E2 at 40 ng/h (Days 13-16) retarded fetal and placental growth but did not affect survival. The rat embryo is highly sensitive to elevated maternal estradiol concentrations over much of gestation. The early lethal effect implies that endogenous E2 production is carefully regulated to maintain pregnancy; the latter growth-retarding effect suggests that E2 may have a role in the normal control of fetal growth.

Effects of unilateral ovariectomy with compensatory hypertrophy on ovarian blood flow, oxygen consumption and progestin secretion in the 16-day pregnant rat.

Stimulated ovulation with resultant multiple corpora lutea (CL) can result in lower progesterone levels than expected from the increased luteal tissue mass. Unilateral ovariectomy (ULO) was used to increase CL number in rats and determine whether this would compromise luteal tissue blood flow, oxygen consumption and progestin secretion. All investigations were performed in vivo, using a venous outflow technique on Day 16 of gestation, when progesterone secretion is maximal. ULO, performed before pregnancy, doubled CL number and total CL mass in the remaining ovary of six treated compared to five control rats. Growth of CL was not affected. The rate of ovarian blood flow (microL min(-1) mg CL(-1)) fell to 47% of control levels in ULO animals and progesterone secretion (microg h(-1) mg CL(-1)) to 68%. Secretion of the minor progestin, 20alpha-hydroxypregn-4-en-one was not affected. Tissue oxygen consumption was maintained despite the reduction in blood flow by an increase in oxygen extraction from arterial blood. These results suggest that overcrowding of CL in ULO-stimulated rat ovaries compromises luteal tissue blood flow and subsequently progesterone secretion.

A prospective study of psychosocial stress and fertility in women.

The objective of this study was to compare average stress levels during the month of conception to those of previous infertile months. We postulated that stress level during the actual month of conception would be lower than that during previous non-conception cycles. Thirteen normal women from the general community, who were attempting pregnancy, kept daily records of coital activity and basal body temperature, and twice a month completed self-administered questionnaires and provided a 12 h overnight urine sample. On average, women reported significantly more favourable mood states on standard psychometric tests, during the month of conception than during the previous non-conception cycles. In addition, they felt significantly less 'hassled' during the month of conception. However, mean urinary hormone excretion of adrenaline, noradrenaline and cortisol did not significantly differ between conception and non-conception cycles and there was little relationship between the psychological measures of mood state and excretion of adrenaline and cortisol. There was no evidence of increased coital frequency during the month of conception when mood states were improved, suggesting that stress effects on libido were unlikely to account for the findings. The results support the conclusion that psychosocial stress influences fertility in females but as yet mechanisms remain unclear.

Direction of blood flow and changes in resistance of major arteries supplying the ovary of the pregnant rat.

In this study, we examined changes in vascular resistance contributing to increased ovarian blood flow in the pregnant rat. Ovarian blood flow was monitored in vivo using a venous outflow cannulation technique in nonpregnant rats and in pregnant rats at Day 16 and Day 22, and increased from 0.18 +/- 0.02 to 0.81 +/- 0.09 and 1.02 +/- 0.08 ml min(-1) ovary(-1) (mean +/- SEM; n = 7, 7, 6), respectively. Intrinsic vessels within the ovarian complex accounted for 81%, 73%, and 70% of total resistance to ovarian blood flow. Of the two major extrinsic supply vessels, from one-half to two-thirds of the ovarian blood was derived from the uterine artery, and the ovarian artery never contributed to uterine blood flow. These results indicate that the major supply vessels are unlikely to limit ovarian blood flow, even near term when competing demand by the gravid uterus reaches a peak. The finding that ovarian blood flow is derived predominantly from the uterine artery may relate to local mechanisms that influence ovarian function and fetal growth.

Effects of noradrenaline on blood flow, progesterone secretion and oxygen consumption in the intact ovary of rats on day 16 of pregnancy.

The effects of noradrenaline on the rates of secretion of ovarian progesterone and 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OHP), blood flow and oxygen consumption were examined in rats on day 16 of pregnancy. A modified venous outflow technique was used to infuse noradrenaline directly into the ovary, without recirculation, and to monitor subsequent changes in the ovary. Noradrenaline was infused for periods of 10 min at a low and a high concentration, which achieved effective blood concentrations of about 6.25 and 25 ng ml-1, respectively. Each period of noradrenaline infusion was interspersed by a 10 min period of infusion of its ascorbic acid carrier. Two series of infusions of low and high concentrations of noradrenaline were carried out on each rat. Neither the infusion of the ascorbic acid carrier nor of the low concentration of noradrenaline had any effect on ovarian progestin secretion. The high concentration of noradrenaline reduced blood flow by 30% but had no apparent effect on progestin secretion or oxygen consumption. Collectively, these findings question the generally accepted view that noradrenaline has a physiological role in the regulation of progesterone secretion. Further, putative luteotrophins need to be examined in the intact ovary as well as under in vitro and indirect in vivo conditions to determine their physiological role.

Spacing of fetuses and local competition in strains of mice with large, medium and small litters.

The tendency for fetuses to be evenly spaced along the uterine horn and the relationship of this to local competition between fetuses was examined in three strains of mice which characteristically produce large, medium and small litters. Local competition was assessed by correlating, within each uterine horn, the weight of each fetus or placenta with the mean distance to its immediate neighbours. Weights and distances were measured on day 19 of gestation, on the day before expected parturition and distances only on day 7. Average litter sizes (live fetuses) were 16.3 +/- 0.9, 11.7 +/- 0.6 and 7.2 +/- 0.5 (mean +/- SEM) in the large, medium and small litter strains, respectively (n = 7, 7 and 10, respectively). On day 19, the mean distance between fetuses was significantly less (P < 0.05) in the large strain (10.1 +/- 1.0 mm) than in the medium (14.0 +/- 1.2 mm) or small (13.5 +/- 1.0 mm) strains. Evenness of spacing, expressed as the standard deviation of distances between fetuses divided by the mean distance, improved from day 7 to day 19 of gestation in all three strains and effectively prevented local competition between fetuses in the medium litter (r = 0.04) and small litter strains (r = 0.17), but not in the large litter strain (r = 0.45, P < 0.01). Thus, local crowding does not seem to be detrimental to fetal growth in mice, except in strains specifically bred for large litters.

Structural and functional reserve of steroidogenic membranes in stimulated luteal cells of pregnant rats.

A comparison was made of the ultrastructural features of the remaining corpora lutea (CL) of five unilaterally ovariectomised and five control pregnant rats. Unilateral ovariectomy (ULO) was carried out on Day 8 of gestation; this treatment has been shown to double the normal rate of progesterone secretion by the remaining ovary within 8 days. On Day 16, the ovaries from both ULO and control rats were examined stereologically. The mass of luteal tissue remaining in ULO rats was only 44% of that in the controls, but their plasma progesterone concentration was 81% and not significantly different from the control value. The CL were 10% heavier in ULO rats and the amount of luteal cell cytoplasm per CL was 21% greater. The percentage of the CL occupied by luteal cells was 15% greater in ULO rats but the interstitial space was 50% less. There was no significant change in the percentage of the luteal cell cytoplasm occupied by cytosol, agranular endoplasmic reticulum (AER), mitochondria and electron-dense granules. The surface area per unit cytoplasmic volume of AER and outer and inner mitochondrial membranes (OMM and IMM, respectively) was not affected. However, expressed per CL, both the AER and IMM membrane surface areas were increased by around 30%. These morphometric changes would only account for about 30% of the reported increase in hormone secretion by the CL of ULO rats, and they suggest that the CL of Day 16 pregnant rats may have reached their optimal structural condition.

Changes in ultrastructure of transport systems and in rates of progestin secretion in the corpus luteum during late pregnancy in the rat.

Morphometric studies have confirmed that the corpus luteum (CL) of the pregnant rat contains luteal cells with numerous microvilli which directly face an extensive network of sinusoidal capillaries. From this it has been suggested that extensive development of transport structures is necessary to support progesterone synthesis and secretion. The present study was carried out to determine whether these transport structures could be related quantitatively to different rates of total progestin (progesterone plus 20 alpha-hydroxypregn-4-en-3-one) secretion reported to be 32, 10, and 23 micrograms/hr per ovary on day 16 and the morning (AM) and afternoon (PM) of day 22, respectively. Histological analysis was carried out on two CL, fixed by immersion, from each of five rats, at each stage of gestation. The important findings to emerge were that when the progestin secretion rate was greater, there was a significant increase in surface specializations on the luteal cell and a thickening of the capillary walls. There was also a greater volume of interstitial space between luteal cells and capillaries. However, due to the development of microvilli and unevenness in the capillary wall, the physiological diffusion distance (harmonic distance) between luteal cell cytoplasm and blood was not increased. Collectively, these results show that changes in the rate of progestin secretion are accompanied by significant, although disproportionate, changes in transport structures and suggest that the latter are important in supporting luteal function.

Quantitative changes in steroidogenic organelles in the corpus luteum of the pregnant rat in relation to progestin secretion on day 16 and in the morning and afternoon of day 22.

The present study was carried out to determine whether the major steroidogenic organelles of luteal cells quantitatively reflect variations in ovarian steroid secretion rates during pregnancy in the rat. Assessments were made on day 16 and in the morning (AM) and afternoon (PM) of day 22 (term is day 23). Ovarian steroidogenesis differs both quantitatively and qualitatively between these stages of pregnancy, so together they provide an ideal physiological model to study structural-functional relationships in the ovary. Corpora lutea of five rats were examined at each stage after progesterone and 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OHP) secretion rates had been determined by a venous outflow technique. Total progestin secretion (progesterone plus 20 alpha-OHP) fell from 32.5 +/- 5.2 to 9.8 +/- 1.2 micrograms/hr per ovary (mean +/- SEM) between day 16 and day 22 AM but then increased to 22.6 +/- 1.4 micrograms/hr per ovary by day 22 PM. The total volume of luteal cell cytoplasm was slightly greater at day 22 AM and PM than at day 16. Similarly, the volumes of smooth endoplasmic reticulum (SER), lipid droplets, and membrane-bound granules all increased, but the volume of mitochondria decreased slightly. In contrast, the surface areas of SER and the inner and outer mitochondrial membranes did not change between day 16 and day 22 AM but then increased substantially by day 22 PM. Therefore, steroid secretion rates per unit area of steroidogenic membrane showed no consistent pattern over the stages examined.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of progesterone supplementation on the metabolic clearance rate of progesterone in the pregnant rat.

In the pregnant rat, short-term stability of progesterone blood concentrations may involve an active homeostatic mechanism. In the present study, we examined the possibility that the metabolic clearance rate (MCR) of progesterone can respond to a change in progesterone production and thus reduce variation in blood concentrations. Progesterone was administered both acutely and chronically to conscious rats, and the effective production rate, MCR, and blood concentration were monitored on Day 16 of pregnancy. Acute, low-dose progesterone supplementation, which effectively raised production rate by 29%, had no effect on the MCR of progesterone. Acute, high-dose supplementation, which raised total progesterone production by 68%, caused a 35% fall in the MCR of progesterone. Chronically supplemented rats received s.c. injections of progesterone (20 mg) once daily over Days 13-16 of pregnancy. The resultant production rate measured on Day 16 was 114% higher than that in controls, but there was no difference in MCR. Collectively, these experiments demonstrate that no short-term homeostatic mechanism involving the MCR operates to control blood progesterone concentrations in Day 16 pregnant rats. Thus, progesterone homeostasis appears limited to long-term developmental changes rather than short-term physiological control.

Changes in ovarian blood flow and secretion of progesterone and 20 alpha-hydroxypregn-4-en-3-one on day 16 and the morning and afternoon of day 22 of pregnancy in the rat.

During late pregnancy in rats, ovarian secretion of progesterone decreases and that of its reduced metabolite, 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OHP), increases. The present study was undertaken to determine whether changes in ovarian blood flow are consistent with changes in progestin secretion. Rats (n = 5 per group) were examined on Day 16, the time of maximal progesterone secretion, and in the morning (AM) and afternoon (PM) of Day 22, the day prior to parturition. Ovarian blood flow was monitored continuously for 60 to 80 min, and serial samples of arterial and ovarian venous blood were obtained at 20-min intervals for determination of ovarian secretion rates of progesterone and 20 alpha-OHP. Ovarian blood flow increased from 0.38 +/- 0.04 ml/min (mean +/- SEM) on Day 16, to 0.77 +/- 0.05 and 0.78 +/- 0.04 ml/min on Day 22 AM and PM, respectively, whereas the secretion of progesterone decreased from 26.9 +/- 4.0 to 4.5 +/- 1.0 and 3.2 +/- 0.3 micrograms/h per ovary. The secretion of 20 alpha-OHP was similar on Day 16 and Day 22 AM (5.6 +/- 1.7 and 5.4 +/- 1.3 micrograms/h per ovary) but then increased to 18.9 +/- 1.2 micrograms/h per ovary by Day 22 PM. Thus the amount of total progestins secreted per unit rate of blood flow relative to that on Day 16 (100%) fell to 15% and 34% on the morning and afternoon of Day 22, respectively. Clearly, the relative changes in ovarian progestin secretion and blood flow in the rat near term to not conform to patterns observed at luteal regression in some other species.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative comparison of luteal histology in the rat and rabbit: changes from mid- to late gestation.

Progesterone secretion by the corpora lutea (CL) of rats and rabbits declines from a peak, at about Day 16 of gestation, to near term (Day 22 rats and 28 rabbits). However there are major differences between the two species in CL growth and blood flow over this period. In the present work quantitative histological measurements were made of CL at these stages to examine the accompanying structural changes. Eight rats and five rabbits were examined at each stage: standard morphometric techniques were used. There was gross discrepancy between the two species in the histology of their CL at peak secretory activity. Although the proportions of the major tissue components were similar, the rabbit luteal cell (52 pl) was five times larger than that in the rat (9 pl). There was substantially less vascular and interstitial space in the rabbit, all characteristics which might affect transport processes between luteal cell cytoplasm and blood. Over the period examined, there was no change in CL volume in the rat but a 37% reduction in the rabbit due to loss of luteal cells. The vascular space in the rat, however, was reduced, whereas that in the rabbit declined only in proportion to the overall decrease in CL volume. These results show that structurally there is a substantial difference in patterns of early regression between the two species which reflect different mechanisms involved.

Effects of indomethacin on spacing of conceptuses within the uterine horn and on fetal and placental growth in the rat.

In the rat, as in most other polytocous species, fetuses tend to be relatively evenly spaced along the uterine horn, perhaps to minimize possible effects of local overcrowding on placental function and fetal growth. Here we administered 2 mg of indomethacin, in split doses on day 5 of gestation, in an attempt to disturb evenness of spacing and so reveal local overcrowding effects, if any. The effects on spacing, expressed as the coefficient of deviation of distances between neighboring implants (CVd%) and correlations between fetal and placental weights and distance to neighbors, was examined on day 16 and day 22 of gestation to cover the period of rapid fetal growth. Indomethacin markedly affected evenness of spacing; at day 16, CVd% increased from a control value of 19.2 to 50.8% and at day 22 from 27.5 to 41.2%. Despite the increased variability of spacing and consequent local crowding, including examples of conjoined placentas in the treated rats, there was no evidence that these local factors affected placental growth or weight of individual fetuses. Indomethacin, however, had a general effect on placental and fetal growth. At day 16, mean fetal weights were retarded but by day 22 had caught up to those of control litters, and this was accompanied by significant placental hypertrophy. Collectively, these results show that the uterus has sufficient reserve to cope with relatively uneven spacing of fetuses and have provided a model for examining catch-up growth of fetuses and accompanying placental changes.

The metabolic clearance of progesterone in the pregnant rat: absence of a physiological role for the lung.

The metabolic clearance rate (MCR) of progesterone is among the highest for all steroid hormones studied, yet it is difficult to apportion this high MCR to specific organ contributions. The isolated lung has been shown to metabolize progesterone, and since this tissue receives the entire cardiac output, potentially it could make a major contribution to the overall MCR. This possibility was examined in the present study by measuring lung extraction of [3H]progesterone under steady-state conditions in the intact pregnant rat. Anesthetized rats (n = 6) were infused with [3H]progesterone via a femoral vein for 100 min on Day 16 of pregnancy. After the onset of steady state (40 min), four blood samples were obtained at 20-min intervals from the right ventricle and from the aorta, and the concentrations of [3H]progesterone and its metabolites were determined. Throughout the sampling period, mean arterial pressure and heart rate remained stable (two-way analysis of variance), as did the production rate (3.76 +/- 0.35 mg/day; mean +/- SEM) and the MCR (34.8 +/- 3.5 ml/min) of progesterone. Despite this high rate of clearance, there was no difference between the concentration of [3H]progesterone in arterial and right ventricular blood, indicating no net extraction of progesterone during passage through the lung. Furthermore, there was no change in the concentration of either lipid-soluble or aqueous-soluble [3H]progesterone metabolites during trans-lung passage. These observations demonstrate that the lung does not contribute to the MCR of progesterone when measured under physiological and steady-state conditions. Therefore, the relationship, MCR (ml/min) = whole-body extraction (%) x cardiac output (ml/min), is upheld for progesterone in the rat.

Changes in the blood concentrations of progesterone and 20 alpha-hydroxypregn-4-en-3-one during late pregnancy in the conscious rat: a specific role for metabolic clearance rate.

Near term in the rat, the blood concentration of progesterone falls while that of 20 alpha-hydroxypregn-4-en-3-one (20 alpha-DHP) increases. This is generally attributed to changes in ovarian secretion alone, but altered rates of hormone metabolism could also have a role. In the present study, therefore, metabolic clearance rate (MCR), production rate, and peripheral interconversion of progesterone and 20 alpha-DHP were measured on Day 16 of pregnancy, the time of maximal progesterone secretion, and on Day 22, one day prior to parturition. Conscious rats (n = 8 per group) were infused with either [3H]progesterone or [3H]20 alpha-DHP and the dynamics of progestin metabolism were calculated from the resultant isotopic and endogenous progesterone and 20 alpha-DHP concentrations. The blood concentration of progesterone declined by 69% between Day 16 (54 +/- 2 ng/ml) and Day 22 (17 +/- 2 ng/ml), and this was due to the combined effect of a 48% increase in the MCR and a 54% decrease in production rate of progesterone. In contrast, the production rate of 20 alpha-DHP was twofold greater on Day 22 compared to Day 16. As a result, the blood concentration of 20 alpha-DHP increased from 28 +/- 3 ng/ml on Day 16 to 40 +/- 6 ng/ml on Day 22, and this change would have been greater but for a concomitant increase (41%) in the MCR of 20 alpha-DHP. Although peripheral conversion of progesterone to 20 alpha-DHP was similar on Day 16 (transfer constant, 12.8 +/- 0.6%) and Day 22 (12.3 +/- 0.9%), the contribution of this conversion to total 20 alpha-DHP production fell from 32% to 7% between the two days.(ABSTRACT TRUNCATED AT 250 WORDS)

Resistance of the rat embryo to elevated maternal epinephrine concentrations.

This study examined the effects of a chronic maternal infusion of epinephrine on development of the rat embryo. Epinephrine was infused during days 1 to 8, 8 to 15, or 15 to 22 of pregnancy to cover periods of implantation, embryogenesis, and rapid fetal growth, respectively. Infusions were accomplished with osmotic minipumps to avoid repeated handling stress. The infusion rate of 0.125 micrograms/min elevated resting plasma concentrations of epinephrine in nonpregnant rats by about sevenfold (from 0.28 to 1.98 ng/ml). Under these conditions, epinephrine did not affect the number of rats maintaining pregnancy, their litter size, or the numbers of resorptions, fetal deaths, and malformations. Fetal and placental weights were unaffected except for a slight trend for fetal weight to be depressed in larger litters of rats treated during days 15 to 22. It seems that the rat embryo is resistant to elevations of epinephrine concentrations equivalent to those observed under mild to severe stress conditions.