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Can a home-based pelvic examination be used in assessing reproductive morbidity in population-based studies? A Jordanian experience.

RATIONALE: Most estimates of reproductive morbidity in a community are derived from health service-based studies. However, these numbers do not reflect the actual magnitude of the problem because of barriers to health care and differences in health-seeking behaviour. As a result, this study uses an alternative method to measure reproductive morbidities amongst women in a Jordanian community. OBJECTIVE: To assess the validity of a home-based pelvic examination in detecting signs of reproductive morbidity when compared with a clinic-based examination. METHODOLOGICAL DESIGN: Descriptive study in which women were randomly selected from the study area to participate in the study. RESEARCH METHODS: Three hundred and seventy nine women, 18 years and above were randomly selected, and general and pelvic examinations were conducted in each woman's home. Thirty-two of these women were again randomly selected and consented to a second pelvic examination in a clinical setting. INSTRUMENTS: Two trained female obstetricians conducted the pelvic examination which included examination of the vulva, examination of the vagina and a bimanual examination. Outcome measures. Strength of association between the presence or absence of physical signs of reproductive morbidity detected by the home-based pelvic examination and the same signs identified by the clinic-based examination, deemed in this study as the 'truth'. RESULTS: The overall sensitivity, specificity, positive and negative predictive values of the home-based pelvic examination were 66, 86, 69 and 84%, respectively. STUDY LIMITATIONS: The sample size was small, so further studies are recommended to replicate the findings here. CONCLUSIONS: Results suggest home-based pelvic examinations can be used in population-based studies for a comprehensive assessment of women's reproductive morbidities.

Adult↗

Evidence against apoptosis as a major mechanism for reproductive cell death following treatment of cell lines with anti-cancer drugs.

An increase in apoptotic cells may be observed after treatment with chemotherapy, and many authors have assumed that anti-cancer drugs kill cells by inducing apoptosis. The most relevant endpoint of cell death following treatment of tumour cells is loss of reproductive ability as measured by a colony-forming assay, since cells with limited reproductive potential cannot regenerate a tumour. We have therefore investigated the relationship between apoptosis and reproductive cell death following in vitro treatment of mammalian cell lines with anti-cancer drugs. Markers of apoptosis (DNA ladders, TUNEL assay) were evaluated at various times after treatment of Chinese Hamster Ovary (CHO) cells, human bladder cancer MGH-U1 cells, and a murine T-lymphocytic cell line (CTLL-2) with several anti-cancer drugs. These markers were found infrequently, despite the use of doses that cause loss of colony-forming ability, except in CTLL-2 cells. We also transfected and expressed the human pro-apoptotic gene bax and the anti-apoptotic gene bcl-2 in MGH-U1 cells and compared cell survival after drug treatment with that of control cells transfected with the vector alone. Expression of these genes had at most small effects to influence cell survival. We conclude that apoptotic mechanisms had at most a minor role in leading to reproductive death of MGH-U1 and CHO cells after chemotherapy. When apoptosis is observed following treatment with anti-cancer drugs it may be a secondary event which occurs in lethally-damaged cells, leading to their lysis, rather than a primary event that leads to loss of reproductive integrity.

Animals↗

Leucocyte population changes in the reproductive tract of the ewe in response to insemination.

Leucocyte changes after insemination may affect conceptus implantation, but information regarding leucocyte populations in the ruminant reproductive tract is limited. The present study investigated changes in leucocyte populations and distribution in the ovine reproductive tract following oestrus and insemination. Fifteen ewes were mated with a ram for 1 h and their reproductive tracts collected 3, 6, 18, 24 or 48 h later. Another 15 ewes were used as oestrus controls. Tissues were collected from 10 sites in each reproductive tract and stained with haematoxylin and eosin, Toluidine blue and immunohistochemically using a monoclonal CD68 antibody. Luminal mucus smears were collected from seven sites and stained with a modified Wright's stain and immunohistochemically. Neutrophils, eosinophils, mast cells and macrophages were identified and quantified, and temporal changes in their distribution within tissues were examined. Neutrophils and macrophages increased significantly (P < 0.05) in posterior cervical and uterine tissues following insemination. In uterine tissues, neutrophils peaked at 6 h after insemination, whereas macrophages peaked at 18-24 h. Mast cells decreased and eosinophils remained constant. Neutrophils increased significantly (P < 0.05) in the cervical and uterine lumen following insemination. In conclusion, leucocyte population changes after insemination vary between different sites in the ovine reproductive tract and may contribute to pregnancy establishment.

Animals↗

Mating, seminal fluid components, and sperm cause changes in vesicle release in the Drosophila female reproductive tract.

Mating induces changes in female insects, including in egg production, ovulation and laying, sperm storage, and behavior. Several molecules and effects that induce these changes have been identified, but their proximate effects on females remain unexplored. We examined whether vesicle release occurs as a consequence of mating; we used transgenic Drosophila that allow monitoring of secretory granule release at nerve termini. Changes in release occur at specific times postmating in different regions of the female reproductive tract: soon after mating in the lower reproductive tract, and later in the upper reproductive tract. Some changes are triggered by receipt of sperm, others by male seminal proteins, and still others by the act of mating itself (or other unidentified effectors). Our findings indicate that the female reproductive tract is a multi-organ system whose regions are modulated separately by mating and mating components. This modulation could create an environment conducive to increased reproductive capacity.

Animals↗

Genetic aetiology of reproductive failures.

The percentage of couples who have problems with reproduction is growing in industrialised nations. Clear genetic aetiology of reproductive failures can be discovered in at least one-sixth of them. All these couples should undergo a comprehensive genetic examination including karyotyping of both partners. Results were obtained over a period of 12 years (1985-97) when studying couples with reproductive failures by taking their detailed family histories and by cytogenetic analysis of their karyotypes. The study subjects were 410 couples (i.e. 820 persons) with different types of reproductive failure from Prague and its surroundings. In 3.16%, one member had an aberration of autosomes and, in 4.38%, one member had an aberration of sex chromosomes. Of these 7.3% had, besides infertility and/or repeated spontaneous abortions, the birth of a child with a polygenic congenital malformation. A detailed genetic investigation of couples with reproductive failures should not be neglected when trying to find the best treatment.

Journal Article↗

Male reproductive tract lesions at 6, 12, and 18 months of age following in utero exposure to di(n-butyl) phthalate.

In utero exposure of male rats to the antiandrogen di(n-butyl) phthalate (DBP) leads to decreased anogenital distance (AGD) on postnatal day (PND) 1, increased areolae retention on PND 13, malformations in the male reproductive tract, and histologic testicular lesions including marked seminiferous epithelial degeneration and a low incidence of Leydig cell (LC) adenomas on PND 90. One objective of this study was to determine the incidence and persistence of decreased AGD, increased areolae retention, and LC adenomas in adult rats following in utero DBP exposure. A second objective was to determine whether AGD and areolae retention during the early postnatal period are associated with lesions in the male reproductive tract. Pregnant Crl:CD(SD)BR rats were gavaged with corn oil or DBP at 100 or 500 mg/kg/day, 10 dams per group. Three replicates of rats (n = 30 rats per replicate) were exposed from gestation day 12 to 21 and the male offspring allowed to mature to 6, 12, or 18 months of age. Gross malformations in the male reproductive tract and histologic lesions in the testes were similar to those previously described. However, testicular dysgenesis, a lesion of proliferating LCs and aberrant tubules that has not been previously described in DBP-exposed testes, was diagnosed. The incidence of this lesion was approximately 20% unilateral and 7-18% bilateral in the high-dose group and was similar among all ages examined, implicating a developmental alteration rather than an age-related change. AGD and areolae retention were found to be permanent changes following in utero exposure to 500 mg/kg/day of DBP. Decreased AGD was a sensitive predictor of lesions in the male reproductive tract, relatively small changes in AGD were associated with a significant incidence of male reproductive malformations. In utero DBP exposure induced proliferative developmental lesions, some of which would have been diagnosed as LC adenomas by the morphological criteria set forth by the Society of Toxicologic Pathology. However, these lesions were dissimilar to traditional LC adenomas as the LCs were poorly differentiated and the lesions contained aberrant seminiferous tubules. While the morphology and incidence of this DBP-induced testicular developmental lesion has been fully characterized by this study, the detailed pathogenesis warrants further investigation.

Adenoma↗

Measuring reproductive morbidity: a community-based approach, Jordan.

Our objective in this study was to determine the prevalence of reproductive and related nonreproductive morbidities in a group of reproductive-aged women living in Jordan. The study was designed as a two-phase survey. The first phase consisted of a structured personal interview and the second phase was a follow-up physical examination. Three hundred seventeen women aged 18-49 years were randomly selected and answered the questionnaire in the first phase of the study. Two hundred sixty agreed to both the general physical and pelvic examination. The main outcome measures were selected reproductive and related nonreproductive morbidities. Results show reproductive tract infections were diagnosed in 55% of the women, a presumed chlamydia trachomatis genital infection in 40%, and genital prolapse in 22%. As for related nonreproductive morbidities, 14% were diagnosed with a urinary tract infection (UTI), 24% with urinary incontinence, and 40% with anemia. Our results of the study support the idea that in this community, women's health is at risk throughout their reproductive years, not only when they are pregnant or postpartum. We suggest further research in other Jordanian communities as well as solutions addressed to the health care community.

Adult↗

2,4,6-trinitrotoluene-induced reproductive toxicity via oxidative DNA damage by its metabolite.

Several epidemiological studies and animal experiments showed that 2,4,6-trinitrotoluene (TNT), a commonly used explosive, induced reproductive toxicity. To clarify whether the toxicity results from the interference of endocrine systems or direct damage to reproductive organs, we examined the effects of TNT on the male reproductive system in Fischer 344 rats. TNT administration induced germ cell degeneration, the disappearance of spermatozoa in seminiferous tubules, and a dramatic decrease in the sperm number in both the testis and epididymis. TNT increased the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in sperm whereas plasma testosterone levels did not decrease. These results suggest that TNT-induced toxicity is derived from direct damage to spermatozoa rather than testosterone-dependent mechanisms. To determine the mechanism of 8-oxodG formation in vivo, we examined DNA damage induced by TNT and its metabolic products in vitro. 4-Hydroxylamino-2,6-dinitrotoluene, a TNT metabolite, induced Cu(II)-mediated damage to 32P-labeled DNA fragments and increased 8-oxodG formation in calf thymus DNA, although TNT itself did not. DNA damage was enhanced by NADH, suggesting that NADH-mediated redox reactions involving TNT metabolites enhanced toxicity. Catalase and bathocuproine inhibited DNA damage, indicating the involvement of H2O2 and Cu(I). These findings suggest that TNT induces reproductive toxicity through oxidative DNA damage mediated by its metabolite. We propose that oxidative DNA damage in the testis plays a role in reproductive toxicity induced by TNT and other nitroaromatic compounds.

8-Hydroxy-2'-Deoxyguanosine↗

Effects of reproductive condition, season, and site on selected temperatures of a viviparous gecko.

The relationship between thermal and reproductive biology is complex and poorly understood. We measured selected body temperatures (T(sel)) for the viviparous gecko Hoplodactylus maculatus. T(sel) was compared among pregnant females, nonpregnant females, and males from two sites: a cool site with biennially reproducing geckos and a warm site with annually reproducing geckos. T(sel) was measured at five times of day during three seasons and compared with microhabitat temperature (T(top)) and field body temperature (T(b)). T(sel) varied with time of day in all comparisons, and the effect of reproductive condition on T(sel) differed between sites and seasons. At both sites, when T(sel) differed between reproductive conditions, pregnant females had higher T(sel) than nonpregnant females and males. Stage of pregnancy affected the degree of elevation of T(sel). Measurements of microhabitat temperature and field T(b) showed that, even in the warmest season, geckos rarely had the opportunity to achieve T(sel) at the cool site but were able to do so at the warm site. The elevation of T(sel) with pregnancy is extreme in this species (up to 8 degrees C), which suggests that an increase in T(b) is critical to successful reproduction. Interactions between the effects of time of day, season, and reproductive condition on T(sel) must be considered in the assessment of thermoregulation in reptiles.

Animals↗

Inefficiency of lactation in primiparous rats: the costs of first reproduction.

To investigate the energetic costs of lactation in a female mammal in relation to previous reproductive history, we compared the performance of adult female Long-Evans rats that had previously bred (multiparous) with young females that had not previously given birth (primiparous). All litters were standardized to 10 +/- 1 young. We compared maternal production (growth of pups), body mass, and energy intake (food consumption) of mothers, as well as their energy expenditure (resting oxygen consumption). The mass of litters at birth and the growth of pups during lactation did not differ according to reproductive history of the mothers. The body mass of primiparous mothers was less than that of multiparous mothers, and primiparous mothers showed an increase in mass during early lactation. To accomplish the essentially identical production of offspring under these circumstances, the primiparous mothers consumed and expended more energy than the multiparous mothers. This remarkable performance of first-time mothers results in an overall efficiency of energy allocation to reproduction amounting to only 25%, compared with 38% in multiparous mothers. The energetic inefficiency of primiparous female lactation results largely from the excessive expenditures associated with physiological and behavioral performances of first-time reproduction, together with a small component of additional expenditure due to further growth by the primiparous mothers. We suggest that this inefficiency probably contributes to the observed low reproductive success of novice breeders; furthermore, active restraint of fecundity may be an evolutionary response to the constraints of the energetic inefficiency of primiparous breeding by female mammals.

Analysis of Variance↗

Expression and localization of luteinizing hormone receptor in the female mouse reproductive tract.

The presence of the LH receptor (LHR) in nongonadal tissues of the reproductive tract has been reported, but localization studies have not been performed. Our objectives were to demonstrate the presence of LHR in the reproductive tract and to localize receptor expression. Reproductive age rats and mice were obtained and (125)I-hCG binding assays were performed on membrane preparations from the uterus, ovary, liver, and testis. In situ hybridizations were performed using (35)S-labeled antisense and sense RNA probes prepared from nucleotides 1-591 of the mouse LHR cDNA. Specific hCG binding was detected in membrane preparations from the ovary, uterus, and testis but not in the liver in both the rat and mouse. In the ovary, LHR mRNA was localized in theca cells, large follicles, and corpora lutea as expected. In the uterus, LHR mRNA was expressed in stromal cells of the endometrium and in the uterine serosa. Uterine smooth muscle cells had low levels of expression, and the endometrial epithelium was negative. In the oviduct, high levels of LHR expression were noted on the serosa and in subepithelial cells. Oviductal smooth muscle had low expression, and the epithelium was negative. We conclude that functional, nongonadal LHR are expressed in the mouse reproductive tract. The presence and localization of LHR expression in the mouse reproductive tract lay the foundation for transgenic models to address the physiologic role of these receptors.

Animals↗

The effects of circumferential wrist pressure on reproduction accuracy of wrist placement in healthy young and elderly adults.

BACKGROUND: The purpose of this study was to determine the effect of circumferential wrist pressure on reproduction accuracy of wrist placement in healthy young and elderly adults. A convenience sample of 20 young adults having a mean age of 22.9 years and 20 elderly adults with a mean age of 68.2 years participated in the study. METHOD: Blindfolded subjects were asked to actively self-select a neutral wrist position (reference) and then, when signaled, to actively reproduce the previously selected position. Wrist joint reproduction accuracy was assessed under four pressure conditions: no contact, wrist contact, 10 mm Hg, and 20 mm Hg. A single axis dynamic wrist electrogoniometer measured three dependent variables: absolute, constant, and variable errors. Data were analyzed by means of multivariate analysis of variance (MANOVA) for repeated measures. RESULTS: No significant differences in reproduction accuracy under the four pressure conditions for young or elderly adults were found. CONCLUSIONS: Healthy young and elderly adults may utilize existing intrinsic feedback and central control mechanisms to achieve accuracy during a reproduction task. Some subjects in both age groups who entered into the study with high error scores benefited from circumferential pressure by possibly relying on peripheral mechanisms. Further studies are needed to determine the effect of circumferential pressure on subjects with poor reproduction performance.

Adolescent↗

Uterine leiomyomas reduce the efficacy of assisted reproduction cycles: results of a matched follow-up study.

A matched follow-up study design was used to test the hypothesis that pregnancy rates following assisted reproduction procedures do not differ between women with or without intramural or sub-serosal uterine leiomyomas. Women undergoing their first in-vitro fertilization (IVF)-embryo transfer or zygote intra-Fallopian transfer (ZIFT) cycle between January 1993 and June 1995 were included. Cases (women with leiomyomas) were matched 1:1 with the next consecutive control (women without leiomyomas) according to age, number of embryos transferred, embryo grade, and the route of embryo transfer (uterine or Fallopian). Assisted reproduction cycles were performed in an identical manner, independent of the presence or absence of uterine leiomyomas. The main outcomes measured were clinical pregnancy and delivery rates. A total of 182 cycles was evaluated. Of the 91 assisted reproduction cycles performed in the leiomyoma group, there were 34 clinical pregnancies (37%) and 30 deliveries (33%). Of the 91 assisted reproduction cycles in the control group, there were 48 clinical pregnancies (53%) and 44 deliveries (48%). The Mantel-Haenszel estimate of relative risk indicated that the presence of a uterine leiomyoma significantly reduced the chance for a clinical pregnancy or delivery. These findings suggest that leiomyomas are associated with a reduction in the efficacy of assisted reproduction cycles.

Adult↗

Mucin expression and function in the female reproductive tract.

Reproductive tract epithelia are characterized by the presence of a thick, apical glycocalyx. This glycoprotein coat is drastically reduced in the uterus of many species during the time of embryo implantation. Recent studies indicate that mucin glycoproteins constitute a large proportion of the apical glycocalyx. One of these mucins, Muc-1, has particularly important functions at the luminal surface of the uterus and other female reproductive tract tissues. Muc-1 appears to play a dominant role in maintaining a functionally non-receptive uterine surface with regard to blastocyst attachment. Conversion to a receptive uterine state is brought about by the concerted actions of ovarian steroid hormones that in several species also strongly modulate Muc-1 protein and mRNA expression. Muc-1 also appears to serve a general function in protecting reproductive tract mucosa since Muc-1 null mice are particularly prone to bacterial infection. Collectively, these studies indicate that mucins, including Muc-1, play important barrier roles in reproductive processes and protection from bacterial pathogenesis in the female reproductive tract.

Animals↗

Neonatal exposure to potent and environmental oestrogens and abnormalities of the male reproductive system in the rat: evidence for importance of the androgen-oestrogen balance and assessment of the relevance to man.

The effects on reproductive tract development in male rats, of neonatal exposure to potent (reference) oestrogens, diethylstilboestrol (DES) and ethinyl oestradiol (EE), with those of two environmental oestrogens, octylphenol and hisphenol A were systematically compared. Other treatments, such as administration of a gonadotrophin-releasing hormone antagonist (GnRHa) or the anti-oestrogen tamoxifen or the anti-androgen flutamide, were used to aid interpretation of the pathways involved. All treatments were administered in the neonatal period before onset of puberty. The cellular sites of expression of androgen receptors (AR) and of oestrogen receptor-alpha (ERalpha) and ERbeta were also established throughout development of the reproductive system. The main findings were as follows: (i) all cell types that express AR also express one or both ERs at all stages of development; (ii) Sertoli cell expression of ERbeta occurs considerably earlier in development than does expression of AR; (iii) most germ cells, including fetal gonocytes, express ERbeta but not AR; (iv) treatment with high, but not low, doses of potent oestrogens such as DES and EE, induces widespread structural and cellular abnormalities of the testis and reproductive tract before puberty; (v) the latter changes are associated with loss of immunoexpression of AR in all affected tissues and a reduction in Leydig cell volume per testis; (vi) none of the effects in (iv) and (v) can be duplicated by treating with high-dose octylphenol or bisphenol A; (vi) none of the reproductive tract changes in (iv) and (v) can be induced by simply suppressing androgen production (GnRHa treatment) or action (flutamide treatment); and (vii) the adverse changes induced by high-dose DES (iv and v) can be largely prevented by co-administration of testosterone. Thus, it is suggested that many of the adverse changes to the testis and reproductive tract induced by exposure to oestrogens result from a combination of high oestrogen and low androgen action. High oestrogen action or low androgen action on their own are unable to induce the same changes.

Abnormalities, Drug-Induced↗

Function of aquaporins in female and male reproductive systems.

The flow of water and some other small molecules across cell membranes is important in many of the processes underlying reproduction. The fluid movement is strongly associated with the presence of aquaporins (AQPs) in the female and male reproductive systems. It has been suggested that AQPs mediate water movement into the antral follicle and play important roles in follicle development. AQPs are known to be involved in the early stage of spermatogenesis, in the secretion of tubule liquid and in the concentration and storage of spermatozoa. Fluid reabsorption in some regions of the male reproductive tract is under steroid hormone control and could be mediated by various AQPs. Also AQPs take part in the processes of fertilization, blastocyst formation (as the pathway for transtrophoectodermal water movement during cavitation) and implantation. Alterations in the expression and function or regulation of AQPs have already been demonstrated in disorders of the male reproductive system, such as abnormal sperm motility, the abnormal epididymis and infertility seen in cystic fibrosis, and varicocele. This article extensively reviews the distribution of AQPs in mammalian reproductive tissues and discusses their possible physiological and pathophysiological roles.

Amniotic Fluid↗

Effect of reproduction on the bioavailability of calcium, zinc and selenium.

Nutrient needs increase during pregnancy and lactation to support fetal growth and milk synthesis, respectively. Physiological adjustments that are made to meet those needs alter the fraction of ingested nutrient retained, or the bioavailability. Using stable isotopes as tracers, we measured calcium, zinc and selenium homeostasis in women during reproduction. The physiological response, and therefore the bioavailability, of these three minerals differed during reproduction. Calcium absorption increased approximately 2-fold during pregnancy but dropped to values for nonpregnant women during lactation. The calcium needs for lactation were met by renal conservation and bone resorption. In women chronically consuming a low calcium diet, fractional calcium absorption increased to >80% during reproduction. Zinc absorption tended to increase during pregnancy and lactation; renal conservation was not evident at any time during the reproductive cycle. Selenium absorption was high, approximately 80% of intake, in both pregnant and nonpregnant women. Pregnant women conserved selenium by decreasing urinary selenium excretion. Studies defining the impact of maternal status and the dietary mineral source and amount on mineral bioavailability are needed to determine the potential benefits of mineral supplementation during reproduction.

Biological Availability↗

Defining and measuring reproductive concerns of female cancer survivors.

Although women diagnosed with cancer during their childbearing years are at significant risk for infertility, we know little about the relationship between infertility and long-term quality of life (QOL). To examine these relationships, we assessed psychosocial and reproductive concerns and QOL in 231 female cancer survivors. Greater reproductive concerns were significantly associated with lower QOL on numerous dimensions (P<.001). In a multiple regression model, social support, gynecologic problems, and reproductive concerns accounted for 63% of the variance in QOL scores. Women who reported wanting to conceive after cancer, but were not able to, reported significantly more reproductive concerns than those who were able to reproduce after cancer (P<.001). These preliminary data suggest that at least for vulnerable subgroups, the issue of reproductive concerns is worthy of additional investigation to assist cancer survivors living with the threat or reality of infertility.

Adult↗