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PubMed2006

Is intravenous immunoglobulins (IVIG) efficacious in early pregnancy failure? A critical review and meta-analysis for patients who fail in vitro fertilization and embryo transfer (IVF).

PROBLEM: Intravenous Immunoglobulins (IVIG) are widely used off label in the treatment of early reproductive failure. As IVIG is expensive, and may have side-effects, evidence of efficacy is needed. Previous results have suggested that the pre-conception treatment of primary recurrent abortion patients might be effective, but the data set has been too small for adequate statistical power. More recently it has been suggested that IVIG may improve the success rate of in vitro fertilization and embryo transfer (IVF) in patients with prior IVF failures, but clinical trials have given conflicting results that need explanation. Systematic reviews generating inconclusive results have focused on methodological rigor to the exclusion of biological plausibility. METHODS: Review of current basic science of design, measurement, and evaluation of clinical trials and basic science mechanisms providing a rationale for treatment. Meta-analysis of published randomized controlled and cohort-controlled trials (updated with two unpublished data sets) evaluating IVIG treatment in IVF failure patients. Live birth rate was used as the most relevant endpoint. The ability of different sources of IVIG to suppress natural killer (NK) cell activity was determined using a standard (51)Cr-release assay in vitro. RESULTS AND CONCLUSIONS: Meta-analysis of three published randomized controlled trials (RCTs) of IVIG in IVF failure patients shows a significant increase in the live birth rate per woman (p = 0.012; Number Needed to Treat for 1 additional live birth, NNT = 6.0 women). Using live birth rate per embryo transferred, and adding data from two cohort-controlled trials to the meta-analysis further supports this conclusion (overall p = 0.000015, NNT = 3.7 women). Relevant variables appear to include properties and scheduling of the IVIG, and selection of patients with abnormal immune test results. Different IVIG preparations vary significantly in their ability to suppress NK activity in vitro. A rationale for use of IVIG is provided by a review of mechanisms of IVIG action and mechanisms underlying failure of chromosomally normal embryos.

Adult↗

PubMed1995

RASP: a system for the analysis of memory tasks.

The purpose of this paper is to introduce a system for the analysis of memory tasks. The system involves four basic task dimensions, derived from an ecological analysis of memory functioning: Reproductivity (R), Acquisition (A), Sufficiency (S), and Productivity (P). Three studies are reported in which professional memory psychologists were asked to rate sets of standard laboratory and more ecologically relevant memory tasks in terms of the four RASP dimensions. In general, results implied independence across the two sets of tasks between the four dimensions. Interrater reliabilities were found to be modest to high. However, it was suggested that RASP best be used as a tool for understanding the meaningful relations that exist among dimensions within general sets or pools of tasks, for different classes of tasks, as well as for prototypical tasks. We argue that, especially when the relationship between RASP profiles for two particular tasks is crossvalidated by behavioral data, and conflict with assumptions about what memory systems or processes are involved, then there is a potential for conceptual refinement. This refinement could be attained either through an increased theoretical generalization, or through an increased theoretical precision. Based on obtained RASP information at the level of classes of tasks (e.g., episodic vs. semantic) as well as at a prototypical task level (e.g., word recall vs. prose recall), several intriguing memory phenomena are discussed. Finally, we suggest that RASP may serve as a tool for reducing the number of task-specific assumptions of what systems and processes mediate memory performance.

Humans↗

PubMed1999

Chronic pain conditions in women.

There are inconsistent data on the age/sex prevalence pattern of back pain and on chest pain. However, it is possible that for chest pain, the rates are higher in younger women and older men. Neck pain, joint pain, and fibromyalgia all appear to increase with age in both genders, whereas abdominal pain and tension-type headaches decrease with age, and migraine headache and TMD appear to peak in the reproductive years. A concluding example illustrates how epidemiologic data can be used to enhance our understanding of the causes of pain. A higher prevalence in women and a peak prevalence during the reproductive years as seen in TMD suggest that either biologic or psychosocial factors unique to women in this period of life could increase the risk of developing or maintaining this pain. As female reproductive hormones can play a role in migraine, at least for some women, it would be interesting to examine whether hormones play a role in TMD. The situation that occurs when menopause is followed by hormone replacement therapy (HRT) provides a natural experiment similar to a laboratory experiment in which female animals are deprived of the natural sources of hormones and then hormones are replaced exogenously. In women, of course, the decision to receive HRT may be associated with a number of psychosocial variables that might also influence pain. Recognizing these limitations, data from records of a large health maintenance organization were examined to ascertain whether use of estrogen or progestin (or both) in postmenopausal women might be associated with the occurrence of TMD pain and, thus, whether the hormone hypothesis might be worthy of further investigation. More women with TMD than controls used estrogen replacement therapy, and slightly more patients than controls used progestin. The use of estrogen significantly increased the odds of having TMD. Progestin use showed a weaker association, which did not hold up after other factors were controlled. However, the risk of TMD appears to increase with increasing doses of estrogen. A review of the epidemiologic literature indicates that there are definite age and sex differences in the prevalence of many chronic pain conditions. There is little basic information about the source of these differences, such as different onset rates, different probabilities of recurrence, or different durations of pain, or combinations of these in women and men. Nevertheless, a systematic examination of the existing epidemiologic data may be an important step in helping pain researchers to generate hypotheses in the search for a better understanding of chronic pain in both sexes.

Analgesics↗

PubMed1987

Protective legislation, ionizing radiation and health: a new appraisal and international survey.

Restrictive regulations ("protective legislation") on employment conditions of female workers limiting maximum hours of work and prohibiting certain toxic exposures have existed for decades. In some countries, such as the United States, Canada and the Nordic countries, the growth of civil rights and equal opportunity legislation has led to their elimination, either in fact or in practice, and only a small number of disparate regulations for male and female workers still exist. Most other industrialized countries, as well as the International Labour Office of the United Nations, still have active restrictive rules for women's employment. However, restrictive regulation is an area of active policy debate around the world. International examples of the debate on protective legislation are given here. A specific case study of the occupational health standards governing exposure to ionizing radiation is used and its technical rationale discussed as an illustration of the basic issues. These include: overbroad categorization of all women as potential childbearers, no matter what their childbearing intentions; failure to recognize the full range of potential adverse health effects to males; disparate application of the restrictive regulations, generally to occupations or areas of employment that are traditionally held by men, while traditional female jobs with the same exposures are excluded from the regulatory restriction.

Adult↗

PubMed2000

Quantitative and qualitative analysis of the effectiveness of a mechanical method for the isolation of preantral follicles from ovine ovaries.

The preantral follicles are the major source of oocytes and its utilization has been investigated as an important tool to store large numbers of female gametes for further utilization in reproductive programs. The aim of the present study was to perform quantitative and qualitative analyses of the efficacy of a mechanical method for isolating of preantral follicles from the ovaries of fetuses and from nonpregnant and pregnant ewes, using as reference the population of preantral follicles in situ. In the isolation method the ovaries were cut into fragments in the tissue chopper. Then, the suspension was filtered through nylon mesh filters. The number of isolated follicles per ovary was 1655, 4735 and 4770, respectively, for the fetus, nonpregnant ewe and pregnant ewe. The number of in situ preantral follicles per ovary was 32961, 16627 and 17794, respectively, for the fetus, nonpregnant ewe and pregnant ewe. The follicle recovery rate (number of isolated preantral follicles/number of in situ preantral follicles x 100) was higher in adult ewes (26 and 28%, respectively, for nonpregnant and pregnant ewes) than in fetuses (5%). Histological analysis showed that very few preantral follicles (less than 0.26% in situ and 0.46% after the isolation procedure) were degenerated. In conclusion, this study showed that a mechanical method could be used effectively to isolate a large number of intact ovine preantral follicles. In the future, with improvements in culture systems, the isolation of a great number of oocytes enclosed in preantral follicles will make a valuable contribution to the rare breeds and endangered species, agricultural efficiency and basic research in folliculogenesis.

Animals↗

PubMed1984

Spermatotoxicity associated with acute and subchronic ethoxyethanol treatment.

Investigations of the male reproductive toxicity of ethoxyethanol (ethylene glycol monoethyl ether) have been restricted exclusively to histopathological assessments of the testes. The present study consisted of two experiments designed to document the spermatotoxicity of ethoxyethanol (EE) as reflected in evaluations of ejaculated rat semen. The basic strategy involved the evaluation of individual ejaculates recovered from the genital tract of a female rat prior to exposure of the males to EE. Repeated assessments of the ejaculate were made during the experimental phase according to specified protocols. Adult Long-Evans hooded male rats received 0, 936, 1872 or 2808 mg/kg (PO) of EE for five consecutive days. Semen evaluations were then conducted at weeks 0, 1, 4, 7, 10 and 14 after exposure. Males in the highest two dose groups showed declines in sperm counts by week 4 and were essentially azoospermic by week 7. At this time, males receiving the lowest dose of EE also exhibited decreases in ejaculated sperm counts. An increase in abnormal sperm shapes was also observed. Over the ensuing weeks all males exhibited varying degrees of recovery as reflected by increasing ejaculated sperm counts. In a second experiment, males were treated with 0 or 936 mg/kg of EE daily (5 days/week) for 6 weeks with semen evaluations conducted weekly. By week 5, sperm counts were significantly depressed and there was an increase in the number of abnormal shapes. Sperm motility was depressed by week 6. The temporal trends seen in these experiments suggested a differential sensitivity of the spermatocyte stage to EE toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

The WHO Task Force on Vaccines for Fertility Regulation. Its formation, objectives and research activities.

Over the past 18 years, the WHO Task Force on Vaccines for Fertility Regulation has been supporting basic and clinical research on the development of birth control vaccines directed against the gametes or the preimplantation embryo. These studies have involved the use of advanced procedures in peptide chemistry, hybridoma technology and molecular genetics as well as the evaluation of a number of novel approaches in general vaccinology. As a result of this international, collaborative effort, a prototype anti-HCG vaccine is now undergoing clinical testing, raising the prospect that a totally new family planning method may be available before the end of the current decade.

Animals↗

PubMed2001

Aedes albopictus (Diptera: Culicidae): physiological aspects of development and reproduction.

Basic ecophysiological data are presented on the development and reproduction of Aedes albopictus (Skuse) that were reared and maintained at four temperatures between 12 and 32 degrees C. Median larval developmental time from hatching to pupation was correlated inversely with temperature, lasting 7 d at 32 degrees C and up to 28 d at 12 degrees C. Duration of the pupal period also varied from 2-3 d at 32 degrees C to 7-12 d at 12 degrees C. This extension of larval development elongated the phagoperiod and gave rise to larger imagoes. Based on wing length measurements, body sizes varied from 10 to 57 mm3 for females and from 10 to 30 mm3 for males. The caloric protein content at emergence showed a linear and significant regression with body size, independent of sex, treatment, or temperature. Teneral lipid content also followed a linear relationship with body size at warmer temperatures, whereas at low temperatures it increased exponentially with body size. Glycogen was always below 10% of the protein or lipid levels. Reserves at emergence determined median adult survival times, which ranged from 16 d at 32 degrees C to 100 d at 17 degrees C. Access to sucrose solution allowed females to increase their teneral glycogen up to fourfold within 1 wk, and their lipids up to 10-fold within 2 wk. Despite abroad variation, the number of mature oocytes (15-110 eggs per female) was correlated positively with body size, but inversely with the rearing and maintenance temperature. Utilization of the blood meal protein for oogenesis ranged between 35 and 50%, again inversely correlated with temperature; absolute compositions per oocyte were 6.3-6.5 mcal of protein but ranged from 5 to 7 mcal of lipid.

Aedes↗

PubMed2006

Issues to consider for preparing ferrets as research subjects in the laboratory.

The domestic or European ferret (Mustela putorius furo) has been domesticated for thousands of years. Ferrets have been used for hunting and fur production, as pets, and as models in biomedical research. Despite the relatively small numbers used in the laboratory, ferrets have some unique applications including study of human influenza and severe acute respiratory syndrome (SARS)-associated corona virus. They have served as models for peptic ulcer disease, carotenoid metabolism, cystic fibrosis, and drug emesis screening, among others. Most research ferrets are males, due to estrus-related health problems in females. They may be housed conventionally and are easy to care for when their biology and behavior are understood. Due to the small number of ferret suppliers, animals are often shipped long distances, requiring air transport and intermediate handlers. It is important to minimize shipment stress, especially with weanling and pregnant animals. Additional expertise is required for success with pregnant and whelping ferrets and for rearing of neonates. The animals have specific dietary requirements, and proper nutrition is key. Successful housing requires knowledge of ferret behaviors including social behavior, eating habits, a general inquisitive nature, and a species-typical need to burrow and hide. Regular handling is necessary to maintain well-being. A ferret health care program consists of physical examination, immunization, clinical pathology, and a working knowledge of common ferret diseases. Various research methodologies have been described, from basic procedures such as blood collection to major invasive survival surgery. Ferrets have a distinct niche in biomedical research and are hardy animals that thrive well in the laboratory.

Acclimatization↗

PubMed2002

Accumulation of deleterious mutations: additional Drosophila melanogaster estimates and a simulation of the effects of selection.

We report an assay of egg-to-adult viability in full-sibling mutation accumulation (MA) lines derived from a completely homozygous population of Drosophila melanogaster and maintained for 210 generations. A simultaneous evaluation was also made of a large population derived from the same origin and maintained as a control for the same period. We also present computer simulations to explore the possible decline in viability of the control population due to mutation accumulation and the possible effect of selection within and between MA lines. For this purpose, we used two mutational models independent from the data analyzed and based on radically different assumptions. The first model implies a large number of mutations of small effect, whereas the second implies a much smaller number of mutations with much larger effects. The observed rate of decline in mean viability was very small but significant (0.077%). The rate of increase in among line variance (0.189 x 10(-3)) was similar to those obtained previously in the same lines. The simulation results indicated that a model of many mutations of small effect is incompatible with the evolution of the mean viability of the control and MA lines over generations, the distribution of line means after 210 generations of mutation accumulation, and the pattern of line extinction over generations. Basically, this model predicted a large drop in viability, both in the control and particularly the MA lines, that is not observed empirically. It also predicted a rate of line extinction too low in the early generations and too high in the later ones. In contrast, the model based on few mutations of large effect was generally consistent with all the observations.

Animals↗

PubMed2002

Basic properties and annual changes of follicle-stimulating hormone receptors in the testis of horseshoe bats, Rhinolophus ferrumequinum.

The unique reproductive patterns, delayed fertilization in females, and asynchrony between spermatogenesis and mating behavior in males are well documented in bats living in temperate latitudes. The present study was undertaken to examine follicle-stimulating hormone (FSH) receptors in the testis of bats, Rhinolophus ferrumequinum, during the annual reproductive cycle. Male bats were captured at natural roosting sites and testicular preparations were subjected to a radioligand binding assay for FSH receptors. The weight of paired testes increased considerably in the spermatogenic period and decreased from the mating to hibernation periods. Meiotic division in the testis was observed in the spermatogenic period but not the mating period. Serum testosterone concentrations increased in the spermatogenic period and rapidly decreased in the mating period. The binding of FSH was specific for mammalian FSHs and detected primarily in the testis. Scatchard plot analyses of the binding of FSH to bat testicular preparations showed straight lines, suggesting the presence of a single class of binding sites. The affinities (equilibrium association constant) of FSH receptors were consistent throughout the annual reproductive cycle. The specific binding per unit weight of testis and total binding in the paired testes were highest in the mating period and in the spermatogenic period, respectively, among reproductive periods. The accumulation of cyclic adenosine 3', 5'-monophosphate to FSH stimulation was higher in the spermatogenic period than in the hibernation period. These findings suggest that testicular function of bats is associated with seasonal changes in the number of binding sites, while the number per target cell and the activation of adenylate cyclase led by FSH-receptor complex considerably decreases in the hibernation period.

Adenylyl Cyclases↗

PubMed2004

Antenatal care: provision and inequality in rural north India.

The objectives of this paper are to examine factors associated with use of antenatal care in rural areas of north India, to investigate access to specific critical components of care and to study differences in the pattern of services received via health facilities versus home visits. We used the 1998-1999 Indian National Family Health Survey of ever-married women in the reproductive age group and analysed data from the states of Bihar, Madhya Pradesh, Rajasthan, and Uttar Pradesh (n = 11,369). Overall, about three-fifths of rural women did not receive any antenatal check-up during their last pregnancy. Services actually received were predominantly provision of tetanus toxoid vaccination and supply of iron and folic acid tablets. Only about 13% of pregnant women had their blood pressure checked and a blood test done at least once. Women visited by health workers received fewer services compared to women who visited a health facility. Home visits were biased towards households with a better standard of living. There was significant under-utilisation of nurse/midwives in the provision of antenatal services and doctors were often the lead providers. The average number of antenatal visits reported in this study was 2.4 and most visits were in the second trimester. Higher social and economic status was associated with increased chances of receiving an antenatal check-up, and of receiving specific components including blood pressure measurement, a blood test and urine testing but not the obstetric physical examination, which was however linked to ever-use of family planning and the education of women and their husbands. Thus, pregnant women from poor and uneducated backgrounds with at least one child were the least likely to receive antenatal check-ups and services in the four large north Indian states. Basic antenatal care components are effective means to prevent a range of pregnancy complications and reduce maternal mortality. The findings indicate substantial limitations of the health services in overcoming socio-economic and cultural barriers to access.

Female↗

PubMed2006

Lysophospholipid receptors as potential drug targets in tissue transplantation and autoimmune diseases.

New therapies directed at ameliorating or altering autoimmune diseases represent an area of significant medical need. Included amongst autoimmune diseases are problems related to transplantation rejection, as well as a number of neurological diseases such as Multiple Sclerosis (MS). A new group of molecular targets that may lead to novel therapies are lysophospholipid (LP) receptors. A large range of biological activities has been attributed to the actions of these simple phospholipids that include well-studied members lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). Documented cellular effects of these lipid molecules encompass growth-factor-like influences on cells, including but not limited to survival, migration, adhesion differentiation, as well as pathophysiological actions associated with cancer. In turn, these cellular effects have roles in developing and adult organ systems such as the nervous system, cardiovascular system, reproductive system and, of relevance here, the immune system. The mechanisms for these actions can be attributed to a growing family of cognate, 7-transmembrane G protein-coupled receptors (GPCRs), with documented validation through studies utilizing pharmacology, molecular genetics and an enlarging repertoire of chemical tools having agonist or antagonist properties. The growing literature on immunological effects of LP receptors, particularly those mediating the effects of S1P, has suggested possible therapeutic roles for this class of receptors. In particular, entry into humans of a non-selective S1P receptor agonist, FTY720, for kidney transplantation and possibly other indications (e.g., Multiple Sclerosis), has raised prospects for efficacious treatment of human diseases based on LP receptor targets. Here we provide a brief introduction to receptor-mediated lysophospholipid signaling and discuss its basic and potential therapeutic roles in autoimmune-related diseases.

Animals↗

PubMed1989

Cloning of Tetrahymena genomic sequences whose message abundance is increased during conjugation.

A molecular and biochemical inquiry into protein regulation during Tetrahymena thermophila conjugation was carried out in two ways: a two-dimensional gel analysis of newly translated proteins and the molecular cloning of genes whose message abundance is increased. The two-dimensional gel analysis indicated that the synthesis of 32 predominantly basic proteins was stimulated in conjugating cells. The induction of these proteins could not be correlated with length of starvation or with mating type. The transcription pattern and molecular organization of three clones of T. thermophila genomic DNA, selected on the basis of differential hybridization to conjugating or control cell RNA, were investigated. Two of the clones, which were homologous to transcripts detected in conjugating cells, showed no rearrangements between micro- and macronuclear DNA. A third clone was divided into three segments. One segment was homologous to sequences limited to the micronucleus. A second segment hybridized to a large number of restriction fragments of micronuclear DNA digested with HindIII but to only two fragments of macronuclear DNA. A third segment, which was complementary to one transcript in conjugating cells and to two different transcripts in control cells, hybridized to two fragments in micronuclear DNA and one fragment in macronuclear DNA.

Animals↗

PubMed1953

Psychiatric contraindications to pregnancy, with reference to therapeutic abortion and sterilization.

Pregnancy and parturition are not considered the basic causes of associated mental disorders, but as precipitating stresses. Pregnancy and parturition are thought to involve conflicts relating to dependency needs, homosexuality and hostility toward the child and husband. The incidence of psychoses related to pregnancy and childbirth appears to be declining. Therapeutic abortion and/or sterilization are indicated when continuance of pregnancy or future pregnancies would be likely to precipitate severe mental disease. Among the important factors to be weighed in considering a recommendation for abortion or sterilization are: the pattern of previous psychotic reactions (severity, duration, reversibility, relation to pregnancy), the physical constitution of the patient, the religious and other personal beliefs of the patient and her family, the desire for parenthood, and the number of living children.A physician would do well to consult the laws of his state with regard to abortion and to call upon suitable consultation in approved hospitals as safeguards against subsequent legal complications. The legal situation regarding sterilization appears to be less complex.

Abortion, Induced↗

PubMed2002

Reproductive health indicators and outcomes among refugee and internally displaced persons in postemergency phase camps.

CONTEXT: Despite increasing awareness of the importance of reproductive health programs and services for refugee and internally displaced populations, there is a paucity of basic epidemiological data on reproductive health outcomes. OBJECTIVES: To collect data on reproductive health outcomes among refugees and internally displaced persons in postemergency phase camps and compare these outcomes with those of host country and country-of-origin populations. To determine programmatic factors that may affect reproductive health outcomes. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of data collected from August 1998 through March 2000 of 688,766 persons living in 52 postemergency phase camps in 7 countries. Reproductive health outcomes of refugee and internally displaced populations were compared with available data of reference populations within their respective host country and country of origin. MAIN OUTCOME MEASURES: Crude birth rate (CBR), neonatal mortality rate (NNMR), maternal mortality ratio (MMR), percentage of newborns with low birth weight (LBW), and incidence of complications of unsafe or spontaneous abortions. RESULTS: Six of 11 groups had lower CBRs than their country of origin and 5 of 9 groups had lower CBRs than their host country. Four of 5 had lower NNMRs than their country of origin and 6 of 9 had lower NNMRs than the host country. Four of 6 had lower MMRs than their country of origin, and 5 of 6 had lower MMRs than their host country. Seven of 9 had lower percentages of LBWs than in the country of origin and 5 of 9 had lower percentages of LBWs than the host country. Higher CBRs were associated with more recently established camps and higher numbers of local health staff per 1000 persons; and higher percentages of LBW newborns were associated with rainy season, more recently established camps, lower numbers of community health workers per 1000 persons, and camps without supplementary feeding programs. CONCLUSIONS: Refugees and internally displaced persons in most postemergency phase camps had better reproductive health outcomes than their respective host country and country-of-origin populations.

Abortion, Illegal↗

PubMed1983

Effect of anaesthesia and surgery on the pre-S-phase cell cycle kinetics of mitogen-stimulated lymphocytes of previously healthy people.

The influence of general anaesthesia, and of operative surgery, on immune responsiveness was studied in blood obtained from 26 women undergoing laparoscopic sterilization (minor operation group) and in 14 women undergoing abdominal hysterectomy (major operation group). Since immunity depends ultimately on clonal expansion of lymphocytes, the growth potential of peripheral blood lymphocytes was studied in tissue culture by mitogen stimulation. There was no evidence of any change in either the number of responding cells (those that have left the resting G0-phase and responded to mitogen stimulation by entering the G1-phase of the first cycle of growth) or in the rate at which cells grow in volume during the period of study. It was concluded that there was no evidence that anaesthesia, or surgery, impaired this aspect of the immune response in our patients, but the design of the experiments does not allow comment on other aspects of the immune response such as antigen presentation, immunoregulation and effector mechanisms, which are superimposed on the basic clonal expansion mechanisms studied in this investigation. Incidentally, we noted that the standard method for isolation of lymphocytes from peripheral blood frequently yielded highly contaminated preparations: if this fallacy was not appreciated, tests with contaminated lymphocytes could be misinterpreted as showing depression.

Adult↗

PubMed1981

Interactions among endocrine control systems in the regulation of ovarian function.

During sequential physiologic maturation of an individual follicle, the number of granulosa cells increases in excess of 1000-fold, while intra-ovarian concentrations of sex steroids escalate by 100-fold. The recent development of several in vitro ovarian systems has permitted a more extensive and direct assessment of specific mechanisms that control growth and steroidogenesis in granulosa and thecal cells. For example, estradiol and follicle stimulating-hormone seem to promote the production by ovarian cells of low-molecular-weight growth factors, that may participate in granulosa cell proliferation. Luteinizing hormone stimulates the de novo synthesis of prostacyclin by granulosa cells in vitro. Prostacyclin, in turn, may regulate the microvasculature of the maturing follicle and directly stimulate steroidogenesis. The effects of individual hormones are markedly modified by other intraovarian endocrine factors, and by the precise status of cytodifferentiation of the ovarian cells. For example, the actions of prolactin on granulosa-cell steroidogenesis are influenced strikingly by both agonistic and antagonistic interactions between prolactin and estradiol, as well as by the level of granulosa-cell cytodifferentiation attained in vivo. Similar bihormonal intrafollicular interactions are recognizable between estrogen and follicle-stimulating hormone in the early follicle, and between estradiol and luteinizing hormone in the maturing follicle. These interactions are susceptible to more precise examination under defined in vitro conditions. Overall, recent advances in biomedical research continue to elucidate basic molecular mechanisms of hormone action in ovarian cell physiology. Such advances are likely to continue to provide important insights into the pathophysiology of clinical disorders of human reproduction.

6-Ketoprostaglandin F1 alpha↗