Ovrang Djahanbakhch

Peritoneal fluid, endometriosis, and ciliary beat frequency in the human fallopian tube

Endometriosis and infertility are known to be associated, but it is unclear whether endometriosis causes infertility. We used contrast analogue enhancement to study the effect of peritoneal fluid from women with early stage endometriosis on the ciliary beat frequency of human fallopian tube epithelium. We obtained peritoneal fluid from six women with early stage endometriosis and from six fertile women with no evidence of endometriosis to use as controls. Fallopian tubes from hysterectomy specimens were collected from 17 women. The difference in ciliary beat frequency between fallopian tubes exposed to peritoneal fluids of women with and without endometriosis increased with the duration of incubation (mean difference at 24 h 1.35 Hz, 95% CI 0.94-1.75, p=0.01). At 24 h, ciliary beat frequency was significantly lower in the incubations with peritoneal fluid from women with endometriosis than controls (4.29 [0.15] vs 5.64 Hz [0.15], respectively, p=0.001). Impairment of ciliary action in women with endometriosis might reduce fertility.

Importance of sperm-to-epithelial cell contact for the capacitation of human spermatozoa in fallopian tube epithelial cell cocultures

OBJECTIVE To investigate the mechanisms involved in the stimulatory effect of fallopian tube epithelial cell coculture on sperm movement characteristics. DESIGN Human spermatozoa were cultured with human fallopian tube epithelial cell monolayers. A microporous membrane was used to prevent sperm-to-epithelial cell contact. Sperm movement characteristics were measured at 4 and 24 hours. SETTING University hospital and fertility center. PATIENT(S) Voluntary donors. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Movement characteristics of human spermatozoa. RESULT(S) Fallopian tube epithelial cell coculture increased sperm motility, curvilinear velocity, amplitude of lateral head displacement, and hyperactivated motility, mainly at 24 hours, compared with controls. These stimulatory effects were inhibited when a microporous membrane prevented cell-to-cell contact between sperm and fallopian tube epithelial cells. CONCLUSION(S) Physical contact between sperm and epithelial cells in coculture systems seems to be the main factor in stimulating sperm movement characteristics, and this could be the main mechanism of in vivo sperm capacitation.

Alteration in auditory function during the ovarian cycle

This study investigates whether physiological variations in ovarian hormones during the ovarian cycle (OC) are associated with changes in auditory function. Sixteen women with normal hearing underwent auditory tests and simultaneous measurements of the hormone levels four times during OC. The auditory tests included recording of otoacoustic emissions (OAEs), the medial olivocochlear (MOC) suppression and auditory brainstem responses (ABRs). The OC was defined by oestradiol and progesterone serum levels and menstrual cycle dating. A significant spontaneous OAE frequency shift [F(3,114.6)=15.8, p<0.001], with the greatest shift in the late follicular phase (highest oestrogen levels), was observed. Transient evoked OAE levels showed a consistent tendency in an increase in all frequency bands in the late follicular/early luteal stage and a decrease in the late follicular stage; TEOAE inter-session comparison indicated very small statistical differences. The MOC suppression changed significantly during OC [F(3,33.8)=3.2, p=0.036], with significant inter-session difference, lower in session 2 than in session 1 (p=0.019) and lower in session 4 than in session 1 (p=0.007). The ABR wave V absolute latency changed significantly during OC [F(3,33)=3.3, p=0.03], longer in the late follicular phase. There was also a significant positive correlation of TEOAEs and ABR (wave V latency and III-V interval) and significant negative correlation of MOC suppression with oestradiol levels in the follicular phase. The results of this study reflect very small changes in auditory function during OC, and they are suggestive of an increased hearing sensitivity around the time of ovulation.

Tubal transport of gametes and embryos: a review of physiology and pathophysiology

With the advent of assisted reproductive technology in the past three decades, the clinical importance of fallopian tubes has been relatively overlooked. However, successful spontaneous conception requires normal function of the tube to provide not only a conduit for the gametes to convene and embryo to reach the uterine cavity, but also a physiologically optimized environment for fertilization and early embryonic development. In this review, after a brief description of normal human tubal anatomy and histology, we will discuss tubal transport and its principal effectors, including ciliary motion, muscular contractility and tubal fluid. Furthermore, we will discuss the ciliary ultrastructure and regulation of ciliary beat frequency by ovarian steroids, follicular fluid, angiotensin system, autonomic nervous system and other factors such as adrenomedullin and prostaglandins. In the last section, we describe the adverse impact of various pathological conditions, such as endometriosis, infection and smoking on tubal function and ciliary motility.

Screening for Down's syndrome: experience in an inner city health district

Objective To review the experience of Downs syndrome screening in an inner city health district.

Comparison of the growth patterns and morphological characteristics of mechanically and enzymatically isolated fallopian tube epithelial cells

This study set out to compare the growth patterns and morphological characteristics of human fallopian tube epithelial cells isolated: (1) mechanically; and (2) enzymatically. Cells were cultured in medium supplemented with fetal bovine serum and antibiotics and their epithelial nature was established by immunocytochemistry for cytokeratins. Primary cultures were polygonal in shape with centrally located nuclei, irrespective of the isolation method. Cells isolated enzymatically exhibited a higher growth rate, but the survival rate was poor after more than 2–3 passages. Mechanical isolation gave a lower yield of cells, but had a higher survival rate when sub‐cultured, even beyond 8 passages. Thus, mechanically isolated cells might be useful for longer term cultures, whereas enzymatically isolated cells are best only for short‐term work.

Secretory function of the Fallopian tube epithelial cells in vitro: A review

Summary The oviduct provides a specialized environment for the survival and transport of the mammalian gametes to the site of fertilization within well defined time limits. The oviduct environment facilitates the process of fertilization and development of the preembryo. Furthermore, the spermatozoa and the pre-embryo, which differ antigenically from the mother, are not attacked by the immune system, which differentiates them from pathogens. The mechanisms by which all these complex processes are controlled are not fully understood. The disadvantage of cell culture systems for physiological study is that the original histological appearance is lost along with some endocrine and paracrine activities. Cells cultured on glass or plastic surfaces lose the polarization normally present in intact tissues. Premature senescence and de-differentiation may occur. It has been shown that extracellular matrix may stimulate proliferation and prevent dedifferentiation. The use of polarized cell cultures also enable the study of cellular orientation and protein secretion. Culture systems for polarized and non-polarized Fallopian tube epithelial cells have been developed in our laboratory. The subsequent experimental studies have shown that the presence of oviduct epithelial cells has a specific and significant stimulatory effect on sperm capacitation, reversing effects on the blockage of blastocyst formation. The exact mechanism of how the co-culture system achieves this is yet to be elucidated and in this regard, the unique oviduct proteins are possible candidates. Further studies of the epithelial cell cultures directed at the nature of the secretory behavior of these cells, are necessary in order to determine how these cells behave in vitro .

Secretory function of the Fallopian tube epithelial cells in vitro

Summary The oviduct provides a specialized environment for the survival and transport of the mammalian gametes to the site of fertilization within well defined time limits. The oviduct environment facilitates the process of fertilization and development of the preembryo. Furthermore, the spermatozoa and the pre-embryo, which differ antigenically from the mother, are not attacked by the immune system, which differentiates them from pathogens. The mechanisms by which all these complex processes are controlled are not fully understood. The disadvantage of cell culture systems for physiological study is that the original histological appearance is lost along with some endocrine and paracrine activities. Cells cultured on glass or plastic surfaces lose the polarization normally present in intact tissues. Premature senescence and de-differentiation may occur. It has been shown that extracellular matrix may stimulate proliferation and prevent dedifferentiation. The use of polarized cell cultures also enable the study of cellular orientation and protein secretion. Culture systems for polarized and non-polarized Fallopian tube epithelial cells have been developed in our laboratory. The subsequent experimental studies have shown that the presence of oviduct epithelial cells has a specific and significant stimulatory effect on sperm capacitation, reversing effects on the blockage of blastocyst formation. The exact mechanism of how the co-culture system achieves this is yet to be elucidated and in this regard, the unique oviduct proteins are possible candidates. Further studies of the epithelial cell cultures directed at the nature of the secretory behavior of these cells, are necessary in order to determine how these cells behave in vitro .

The Effect of Ovarian Steroids on Epithelial Ciliary Beat Frequency in the Human Fallopian Tube

Using a method that detects variations in light intensity we have studied the effect of ovarian steroids on human Fallopian tube epithelial ciliary beat frequency in vitro. We have found that baseline ciliary beat frequency averages between 5-6 Hz. Cilia from ampullary segments of the Fallopian tube beat significantly faster (5.4 Hz+/-0.2) than those from fimbrial segments (4.8 Hz+/-0.2). There was no significant difference in baseline ciliary beat frequency at any other anatomical site in the Fallopian tube. Incubation with progesterone (10 micromol/l) suppresses human Fallopian tube epithelial ciliary beat frequency by 40-50%. This inhibition was observed at similar magnitudes in all Fallopian tubes studied irrespective of anatomical site. Progesterone-induced reductions in ciliary beat frequency were concentration dependent and prevented by the progesterone receptor antagonist mifepristone (RU486). Oestradiol alone (10 micromol/l) had no effect on ciliary beat frequency at any anatomical site in the Fallopian tube but did prevent the reduction in ciliary beat frequency seen with progesterone when tissues were incubated with these two steroids together.

Angiotensin II receptors and angiotensin II stimulation of ciliary activity in human fallopian tube

Using an antibody (6313/G2) directed against a specific sequence in the extracellular domain of the type 1 angiotensin II receptor (AT1), we demonstrated the presence of angiotensin II (AII) receptors in human fallopian tube. Immunoperoxidase staining for AT1 receptor showed positive staining in the epithelium of the tubal mucosa. The intensity of staining varied depending upon the hormonal status at the time of salpingectomy, being strongest in the proliferative phase of the ovarian cycle and weakest after menopause. Ligand binding assay confirmed that the AII receptor concentration was highest in the mucosa of fallopian tubes from premenopausal women. Mucosa from the ampullary segment had higher concentrations of AII receptor than the fimbrial and isthmic segments in both premenopausal and postmenopausal women. Displacement studies using specific AII receptor subtype antagonists showed that approximately 60% of the total activity could be displaced by CGP42112B (type 2 specific) and 40% by losartan (AT1 specific). Immunoblotting confirmed that the antibody detected a protein of approximately 60 kDa. Functional studies showed that AII had a stimulatory action on tubal ciliary beat frequency, but had no significant effect on myosalpingseal activity. This effect was achieved at nanomolar concentrations of AII; further increases in the AII concentration were without additional effect. The stimulatory effect of AII was inhibited by the specific AT1 antagonist losartan, whereas the type 2 antagonist, CGP42112B, had no effect. The data demonstrate that AII may play an important role in ovum transport and fertility.