Effective tubal transport of ova, sperm and embryos is a prerequisite for successful spontaneous pregnancy. Although there is much yet to be discovered about the mechanisms involved, it is evident that tubal transit is a far more complicated process than initially thought. Propulsion of gametes and embryos is achieved by complex interaction between muscle contractions, ciliary activity and the flow of tubal secretions. Evidence is accumulating of the important and possibly pre-eminent role of ciliary motion in this process; and this review describes current knowledge about ciliary activity and its physiological regulation. There is also a description of the effects on ciliary function of cigarette smoking and various pathological states, including endometriosis and microbial infection, with consideration given as to how altered ciliary activity may impact upon fertility.
Context: Polycystic ovary syndrome (PCOS) represents the most common endocrine abnormality in women of reproductive age. The cause of PCOS remains largely unknown, but studies suggest an intrinsic ovarian abnormality.Objective: The objective of the study was to test our hypothesis that differences in granulosa cell proliferation and apoptosis may underlie abnormalities that affect follicular development.Design: Granulosa cells were prepared from follicular fluid aspirated from 4-to 8-mm follicles of unstimulated ovaries during routine laparoscopy or laparotomy from women with anovulatory PCOS and those with regular ovulatory cycles. Setting:The study was conducted at a university hospital.Patients: Fourteen women with anovulatory PCOS and nine women with regular ovulatory cycles participated in the study. Main Outcome Measures:Immunocytochemistry on granulosa cells to investigate apoptotic and proliferation rates, together with real-time RT-PCR to analyze gene expression profiles of apoptotic regulators, was measured.Results: Significantly lower apoptotic rates were found in granulosa cells from patients with PCOS, compared with women with regular ovulatory cycles (P ϭ 0.004). Lower apoptotic rates were associated with decreased levels of the apoptotic effector caspase-3 (P ϭ 0.001) and increased levels of the anti-apoptotic survival factor cellular inhibitor of apoptosis proteins-2 in the PCOS group that were coupled to higher proliferation rates (P ϭ 0.032). Gene expression profiling confirmed the immunocytochemical findings. Conclusions:Our findings indicate that there are significant differences in the rate of cell death and proliferation in granulosa cell populations in PCOS patients. These are associated with decreased expression of apoptotic effectors and increased expression of a cell survival factor. These results provide new insights that may be useful in developing specific therapeutic intervention strategies in PCOS. (J Clin Endocrinol Metab 93: 881-887, 2008) P olycystic ovary syndrome (PCOS) is a common endocrine abnormality in women of reproductive age, affecting 6.6 -8% of women in this age group (1). It is the main cause of anovulatory infertility and is characterized by chronic anovulation, hyperandrogenemia, and polycystic ovaries on ultrasound scan (2). Abbreviations: Bcl, B-cell lymphoma; BMI, body mass index; cIAP, cellular IAP; DHEAS, dehydroepiandrosterone sulfate; IAP, inhibitor of apoptosis proteins; Mcl, myeloid leukemia cell differentiation protein; PCOS, polycystic ovary syndrome; TUNEL, terminal deoxynucleotidyl transferase biotin-deoxyuridine 5-triphosphate nick end labeling; XIAP, X-linked inhibitor of apoptosis protein.
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.
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