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PubMedDate not supplied

Infertility as a consequence of chlamydial infection of the upper genital tract in female mice.

The effect of infection with Chalmydia trachomatis (mouse pneumonitis biovar) on the fertility of female mice was examined. Mice were inoculated into one ovarian bursa with approximately 10(4) inclusion-forming units of C. trachomatis and were mated five to 16 days later. At sacrifice all mice showed salpingitis or hydrosalpinx in the inoculated oviduct and implantations were found only in the uterine horn contiguous with the noninoculated oviduct. Animals inoculated with tissue culture supernate showed no tubal pathology and had implantations evenly distributed in both uterine horns. Intrauterine inoculation of Chlamydia five to 36 days before mating also resulted in tubal pathology and infertility. Intrauterine inoculation of C. trachomatis one to two days after mating (one to two days before expected nidation) had no effect on the number or distribution of implantation sites as compared with controls. These results demonstrate that chlamydial infection of the upper reproductive tract of mice prior to mating can result in infertility.

Animals↗
PubMed2005

Uterine contractility and embryo implantation.

PURPOSE OF REVIEW: The aim of this article is to assess the importance of uterine contractility in the implantation of human embryos. RECENT FINDINGS: Recent findings show that the receptive phase of the endometrium seems to occur in close association with the appearance of pinopodes and endometrial integrins that may be activated by the IL-1 system. Throughout the menstrual cycle wavelike activity patterns of the uterus were identified with adequate wave patterns appearing to be related to successful reproduction in spontaneous cycles and in assisted reproduction. Such patterns are controlled by steroid hormones. Embryo attachment to the predecidualized endometrium and its invasion may be determined by the expression of proteolytic enzymes that require uterine quiescence for implantation. The uterine activity was detected both in vitro and in vivo by using invasive intrauterine pressure and noninvasive ultrasound approaches. Progesterone promotes local vasodilatation and uterine musculature quiescence by inducing nitric oxide synthesis in the decidua. At present, until new evidence emerges to demonstrate otherwise, the effects of progesterone are, directly or indirectly, the only determinant of endometrial preparation for embryo nidation, with the induction of uterine quiescence being one of these effects. SUMMARY: Adequate uterine contractility may provide for gamete/embryo transportation through the utero-tubal cavities and successful embryo implantation in spontaneous or assisted reproduction. Inadequate uterine contractility may lead to ectopic pregnancies, miscarriages, retrograde bleeding with dysmenorrhea and endometriosis.

Catheterization↗
PubMed2006

Uterine contractility and embryo implantation.

PURPOSE OF REVIEW: The aim of this article is to assess the importance of uterine contractility in the implantation of human embryos. RECENT FINDINGS: Recent findings show that the receptive phase of the endometrium seems to occur in close association with the appearance of pinopodes and endometrial integrins that may be activated by the IL-1 system. Throughout the menstrual cycle wavelike activity patterns of the uterus were identified with adequate wave patterns appearing to be related to successful reproduction in spontaneous cycles and in assisted reproduction. Such patterns are controlled by steroid hormones. Embryo attachment to the predecidualized endometrium and its invasion may be determined by the expression of proteolytic enzymes that require uterine quiescence for implantation. The uterine activity was detected both in vitro and in vivo by using invasive intrauterine pressure and noninvasive ultrasound approaches. Progesterone promotes local vasodilatation and uterine musculature quiescence by inducing nitric oxide synthesis in the decidua. At present, until new evidence emerges to demonstrate otherwise, the effects of progesterone are, directly or indirectly, the only determinant of endometrial preparation for embryo nidation, with the induction of uterine quiescence being one of these effects. SUMMARY: Adequate uterine contractility may provide for gamete/embryo transportation through the utero-tubal cavities and successful embryo implantation in spontaneous or assisted reproduction. Inadequate uterine contractility may lead to ectopic pregnancies, miscarriages, retrograde bleeding with dysmenorrhea and endometriosis.

Embryo Implantation↗
PubMed1976

Decidualisation in the prepuberal rat uterus.

Decidualisation has been experimentally induced in the prepuberal rat. It is morphologically similar to that obtained in the adult. The cytodifferentiation includes the formation of binucleated cells and extensive specialised cellular junctions. Furthermore, blastocysts from adults transferred into uterine horns of immature specimens implant and develop, indicating that the decidual response they induce is functionally comparable to the uterine response at the time of nidation in the fertilised adult. The model of the experimental decidual induction in the immature is used to study the ontogenic processes of uterine maturation. Preliminary observations indicate that the 7-10-days period might be of significance in the maturation of the rat uterus.

Age Factors↗
PubMed1995

A new approach to methotrexate and lipiodol suspensions for ectopic pregnancy: preliminary in vitro and animal experiments.

OBJECTIVES: To measure and evaluate the in vitro release of MTX from suspensions of methotrexate (MTX) and lipiodol (LPD), and to investigate the MTX concentration and fertility rate using an animal model. METHODS: This study was divided into three components: a) An in vitro Release Study, b) Animal Study No. 1 (concentration of tissue and plasma levels), and c) Animal Study No. 2 (fertility rate after MTX suspension). RESULT: The releasing rate in vitro was more rapid with MTX-S (MTX dissolved in saline) than with either MTX-LPD (MTX dissolved in lipiodol) or MTX-LPD-PC (MTX suspended in lipiodol and phosphatidylcholin, i.e., MTX suspension). The tissue concentration tended to be higher with an MTX suspension than with MTX-S. There was no significant difference in the fertility rate or the nidation index among the 3 groups (Groups 1, 2, and 3). CONCLUSION: The injection of an MTX suspension is useful for increasing the tissue concentration and maintaining the long-term effectiveness of MTX, and this technique might offer a new approach in the treatment of ectopic pregnancy (EP) or in second-line therapy for persistent EP.

Animals↗
PubMed1985

Training in tubal microsurgery.

The restoration of normal tubo-ovarian function was investigated in a training programme using oviduct anastomosis in the rabbit as an experimental model. Ovulation rate, pregnancy rate, nidation index, implantation failure index and degree of adhesions were used as parameters. More than 100 anastomoses had to be performed to reach a perfect degree of atraumatic, function-restoring surgery. It is concluded that the most difficult aspect in female infertility surgery is not the use of the operating microscope but the experience in applying the principles of atraumatic surgery.

Animals↗
PubMed1984

Fulguration versus resection of experimental endometrial peritoneal implants in the rat.

Endometriosis was induced in 20 rats. Treatment by diathermy was compared to treatment by microsurgical resection of endometrial implants. No significant differences were found between the 2 groups regarding ovulation, nidation index or pregnancy rates but significant difference in the extent of adhesion formation after surgery was evident. There were fewer adhesions in the microsurgical group. As the adhesions here were periuterine (and not peritubal as in the human) this could explain the lack of impact on the actual fertility of these rats.

Animals↗
PubMed1983

Immunological studies of human trophoblast: markers, subsets and functions.

People have many different reasons for wanting to know how the allogeneic relationship in normal human pregnancy is successful, but this question is far from being answered. Meanwhile, investigators will continue to use the ideas, approaches and tools with which they have experience and in which they have placed their confidence. Some study the factors which regulate immune functions in the fetus (for review see Murgita & Wigzel 1981); other focus more on the mother (for review see Rocklin et al. 1979); while yet others examine specialized aspects of abnormal pregnancies such as spontaneous abortion (Gill 1983). Although no one knows how the system operates to favor pregnancy, our particular bias is that trophoblast is the driving force which makes it work; for, without trophoblast, there is no pregnancy. This prejudice grew from our early observations of immunopathology in normal placentae (McCormick et al. 1971, Faulk et al. 1974, Faulk et al. 1980b, and reviewed by Faulk & Fox 1982) and was extended and amplified by experiments which showed that trophoblast, as well as antibodies to trophoblast, were able to impede allogeneic recognition as measured by specific inhibition of the mixed lymphocyte culture reaction (McIntyre & Faulk 1979 & 1979a). For a variety of reasons, many laboratories became interested in trophoblast-antigen biochemistry, and a burst of publications appeared on this subject (Faulk et al. 1977, Whyte & Loke 1979, Ogbimi et al. 1979, see review by Johnson et al. 1980). Some of this work confirmed and extended an earlier hypothesis from our laboratory that trophoblast membranes could serve as a hapten-carrier system where one group of trophoblast antigens (TA1) was the carrier, and a second group (TA2) was the hapten (Faulk et al. 1978). This hypothesis invoked a concept of trophoblast-lymphocyte cross-reactive antigens, an idea which was subsequently confirmed biochemically by showing human placental cell-surface antigens on peripheral blood lymphocytes (Hamilton et al. 1980). McIntyre and Faulk (1982, 1982a) later showed that these antigens were allotypic, and data have been provided in the above paragraphs to show that these components of trophoblast membranes are capable of serving as immunogens to stimulate the mother to mount immune recognition of her blastocyst. Indeed, it is presently our interpretation that successful nidation depends upon maternal recognition of the blastocyst, and that a lack of recognition results in spontaneous abortion, sometimes occurring so early that the mother is not aware that she was pregnant (Miller et al. 1980).(ABSTRACT TRUNCATED AT 400 WORDS)

Abortion, Habitual↗
PubMed1989

Levels of interleukin-2 receptor in serum of patients during the menstrual cycle and following embryo/gamete transfer.

In an attempt to establish whether nidation elicits a measureable systemic immunologic response in vivo, levels of interleukin-2 receptor (IL-2R) have been determined in serum drawn from 34 pregnant patients (IUP) immediately before embryo/gamete transfer, and 7 and 14 days later. For comparison, these same values were determined for 41 subjects who did not conceive, and for 18 who spontaneously aborted (SAB) during the first trimester of gestation. Serum IL-2R values were near 320 U/ml and did not differ between days within outcomes, or within days between outcomes. Furthermore, levels of IL-2R and beta-hCG in serum were not interrelated on days 7 or 14 of pregnancy (SAB or IUP). Serum IL-2R levels did not change during the menstrual cycle. The present results appear to traverse presumptive elements of existing hypotheses of "placental immunotropism."

Chorionic Gonadotropin↗
PubMed1996

Cytokines of the human reproductive tract.

PROBLEM: How is it possible that the female genital tract immunologically does not reject spermatooa not the preimplantation and nidating embryo? METHODS: Four fluids of the human reproductive tract, i.e., human oviductal fluid (hOF), follicular fluid (FF), amniotic fluid (AF), and seminal plasma (SP) were investigated by specific ELISA for 18 cytokines. The concentrations, presence or absence of these compounds were evaluated for their possible role in the immunology of the reproductive process. RESULTS: Stem cell factor and IL-11 were detected in all reproductive tract fluids examined whereas large amounts of IL-1 beta and IL-1RA was found in AF and hOF. Follicular fluid revealed IL-2. HOF contained IL 2, IL-6, IL-8, TNF-alpha, MIP-1 alpha, IFN-gamma, and high levels of IL-1 beta, IL-10, IL-1RA, and sIL-2R. Amniotic fluid contained sIL-2R, IL-8, IL-1 beta, IL-1RA, IL-6, TNF-alpha, and MIP-1 alpha. No IL-12 or IL-13 was detected in hOF follicular fluid or amniotic fluid. Almost no free TGF-beta 1 or TGF-beta 2 was found in any reproductive tract fluid except seminal plasma. Seminal plasma contained large quantities of free TGF-beta 1 (9,220 +/- 3,635 pg/mL) in addition to large quantities of latent TGF-beta 2 (2,933 +/- 2,169 pg/mL) and TGF-beta 1 (71,000 +/- 3,240 pg/mL). Furthermore, considerable concentrations of IL-8 (1900 +/- 374 pg/mL) and sIL-2R (350 mu/mL) exist in seminal plasma. CONCLUSIONS: HOF contains a high level of IL-10 (588 +/- 304 pg/mL), a powerful immune suppressor which probably plays a role in regulating immune responses in the fallopian tube and possibly in the endometrial cavity. Our observations suggest that seminal plasma with its huge content of TGF beta provides immune protection for sperm. Unfortunately, such high concentrations of TGF beta may also inhibit an immune defense in any organ in which semen is deposited.

Amniotic Fluid↗
PubMed2006

In vivo correlation between IL-1beta concentration in uterine fluid and integrin expression pattern in infertile women.

PROBLEM: To evaluate the possible correlation between interleukin-1beta (IL-1beta) and integrin expression. METHOD OF STUDY: Endometrium and uterine fluid from 77 infertile women and 24 fertile, healthy control were studied with immunohistochemistry and enzyme-linked immunosorbent assay for the presence of IL-1beta and integrin alphaVbeta3 and alpha4beta1 expression. RESULTS: Highest expression of alphaVbeta3 was found in epithelium and glands in endometria from fertile women. There was no positive correlation between IL-1beta and integrin expression pattern. CONCLUSION: This study confirms the importance of alphaVbeta3 as molecular marker of receptive phase. Also supports the views that synchrony in development of endometrium is necessary for successful nidation. There was however, contrary to results of previous in vitro studies, no positive correlation between IL-1beta and endometrial integrin patter expression.

Adult↗
PubMed1995

Histopathology of postpartum placental sites in mink (Mustela vison) exposed to polychlorinated biphenyls or fractions thereof.

Polychlorinated biphenyls (PCB) cause reproductive failure in mink. Ovulation and nidation occur, but the fetuses die during gestation. The toxicity of different chlorinated biphenyl (CB) congeners differs markedly. Dioxin-like congeners with no (0-ortho CBs) chlorine in the ortho position to the biphenyl bond are considered to be highly toxic. Altogether, 13 groups of 10 female mink (Mustela vison) were exposed to PCB or CB fractions thereof during the reproductive season of 1988 and 1989. In 1988, one group of mink received 2 mg/day of Clophen A50 and five groups received single fractions thereof or synthetic 0-ortho CB in their diet. In 1989, one group received 1.64 mg/day of Aroclor 1254 and six groups received combinations of fractions thereof. The daily amounts of the fractions administered per animal were equivalent to those present in 2 mg of Clophen A50 or 1.64 mg of Aroclor 1254. After administration for 3 months in both experiments, the animals were killed 5 days after parturition. Histological examination focused on the placental sites. The most involuted placental sites were those of early fetal death in primiparous, non-whelping animals in the 1989 experiment. The least involuted placental sites, displaying a hyperplastic and pleomorphic uterine luminal epithelium, in which proliferating cell nuclear antigen (PCNA) was present, were those of late fetal death in biparous, non-whelping animals in the 1988 experiment. The survival of the fetoplacental unit was related to PCB exposure. The histology of the placental sites seemed only to be related to the survival time of the fetuses and to the number of former reproductive seasons.

Animals↗
PubMed1997

Uterine pinopodes in peri-implantation human endometrium. Clinical relevance.

Current clinical studies indicate the existence in the human of an "implantation/nidation window," similar to that observed in animal models. During this short period of uterine receptivity, the formation of pinopodes on the apical cell membrane of the endometrial epithelium is a consistent morphological event, observed in a number of species studies including the human. In order to develop a specific marker of the implantation window in clinical practice, we have investigated the kinetics of pinopode formation through sequential endometrial sampling under various hormonal conditions. Our results show that the implantation window in humans, according to this marker, lasts less than 48 hours, and the timing of its opening is dependent on the hormonal treatment applied, occurring earlier in cycles following ovarian stimulation and later in cycles induced by hormone replacement treatment. Furthermore, the timing varies among different individuals under the same treatment. These findings suggest that examination for pinopodes in endometrial samples can be highly useful in infertility treatment and research for the assessment of the nidation window on an individual basis. Our preliminary data strongly support the value of this assessment for better timing of ovum transfer, leading to an increase in implantation rates. Studies are now in progress on the expression of other endometrial signals present in relation to the pinopodes.

Embryo Implantation↗
PubMed2001

Maternal-embryonic cross-talk.

The human menstrual cycle evolved to prepare the uterus for blastocyst implantation, which is fundamentally under the control of gonadal steroids. Ovarian hormones induce marked morphological, physiological, and biochemical changes within reproductive tissues. These changes in turn induce alterations in the biosynthetic activity and release of a myriad of locally produced proteins into the microenvironment of the reproductive tract. These same factors may be further modified by proteins secreted by the developing embryo and accompanying cumulus cells in intimate contact with reproductive epithelium in a network signaling process. Communication is not one-way, but rather maternal-embryonic cross-talk may occur as maternal proteins are secreted into the microenvironment of the oviduct and uterus, facilitating fertilization and early embryo development and serving as homing beacons for blastocyst nidation. The communicating language facilitating this dialogue includes cytokines, growth factors, angiogenic factors, apoptotic factors, adhesion molecules, and, potentially, homeotic genes.

Animals↗
PubMed2001

Uterine contractility: vaginal administration of the beta-adrenergic agonist, terbutaline. Evidence of direct vagina-to-uterus transport.

Spontaneous uterine contractility during the menstrual cycle is required for menstruation, gamete transport, and, most likely, embryo nidation. Abnormal uterine contractility has been linked to dysmenorrhea, a condition associated with painful uterine cramping. Based on previous studies with progesterone, we have postulated the existence of a portal system that is responsible for some degree of direct vagina-to-uterus transport of administered compounds (i.e., the "first uterine pass effect"). It is possible that treatment with uterorelaxing substances, particularly beta-adrenergic agonists, may alleviate the uterine discomfort that accompanies dysmenorrhea. However, side effects encountered with oral administration of beta-agonists limit their utility. Alternatively, vaginal delivery of beta-agonists could solve this dilemma by enhancing their efficacy and reducing side effects. Therefore, in the current study we used hysterectomy specimens and an in vitro uterine perfusion system to test the vagina-to-uterus transport of [3H]terbutaline, a well-known beta-agonist. With the use of autoradiographic and scintillation counting techniques, our results clearly show progressive diffusion of labeled terbutaline from the rim of vaginal tissue through the uterus during the first 12 hours of perfusion. This indicates that uterine targeting of terbutaline can be accomplished through vaginal administration, suggesting a new therapeutic modality in women's health care.

Administration, Intravaginal↗
PubMed2002

Progesterone-mediated endometrial maturation limits matrix metalloproteinase (MMP) expression in an inflammatory-like environment: a regulatory system altered in endometriosis.

The human endometrium exhibits regular cycles of growth, differentiation, and breakdown in response to changing levels of ovarian steroids. Following the tissue loss and repair processes of menstruation, rising levels of estradiol initiate a development-like process leading to a complete restructuring of the endometrial surface. In contrast, while under the predominate influence of progesterone, proliferation declines as cell-specific differentiation prepares the endometrium for pregnancy over a 5- to 6-day period. In the absence of nidation, steroid support is lost; the endometrial surface begins a complex process of tissue breakdown and bleeding, producing a viscous mixture of cellular debris within a bloody menstrual effluent. Although most of the menstrual fluid exits the body, reflux of some material occurs in most women, providing a poorly understood opportunity for ectopic endometrial growth and establishment of the disease endometriosis. The cyclic restructuring of the endometrium requires numerous matrix metalloproteinases (MMPs) that mediate normal and pathological tissue turnover throughout the reproductive tract. The expression of multiple MMPs facilitates degradation of extracellular matrix during growth-related remodeling as well as tissue breakdown at the time of menstruation. However, these enzymes are absent during the early and mid-secretory phase and the suppression of endometrial MMPs remains important to maintaining the integrity of the endometrium during the highly invasive events required to establish a normal hemochorial placenta. Several research groups have suggested that steroid-mediated expression and action of MMPs during the menstrual cycle may provide a key mechanistic link between endometrial turnover and the invasive processes necessary for establishment of endometriosis.

Endometriosis↗
PubMed1967

Development of mouse ova in explanted oviducts: fertilization, cultivation, and transplantation.

The development of fertilized ova in explanted parts of oviducts was studied from 12 to 36 hours after fertilization, and from 36 to 84 hours after fertilization. No egg mortality during cultivation, nor any slowing of development could be detected in either experiment. It may be presumed that the mortality of mouse ova during the period before implantation has no essential effect on the resulting fertility. During cultivation of oviducts for 144 hours, there occurred in most blastocysts herniation of their walls resulting in a formation similar to the blastocyst, and a migration of a disorganized mass of cells, some of which resembled the giant trophoblastic cells. After transplantation of ova fertilized in vitro to recipients, in four cases there occurred nidation and subsequent normal development of the embryo.

Animals↗