The central thesis regarding the human ovaries is that, although primordial germ cells in embryonal ovaries are of extraovarian origin, those generated during the fetal period and in postnatal life are derived from the ovarian surface epithelium (OSE) bipotent cells. With the assistance of immune system-related cells, secondary germ cells and primitive granulosa cells originate from OSE stem cells in the fetal and adult human gonads. Fetal primary follicles are formed during the second trimester of intrauterine life, prior to the end of immune adaptation, possibly to be recognized as self-structures and renewed later. With the onset of menarche, a periodical oocyte and follicular renewal emerges to replace aging primary follicles and ensure that fresh eggs for healthy babies are always available during the prime reproductive period. The periodical follicular renewal ceases between 35 and 40 yr of age, and the remaining primary follicles are utilized during the premenopausal period until exhausted. However, the persisting oocytes accumulate genetic alterations and may become unsuitable for ovulation and fertilization. The human OSE stem cells preserve the character of embryonic stem cells, and they may produce distinct cell types, including new eggs in vitro, particularly when derived from patients with premature ovarian failure or aging and postmenopausal ovaries. Our observations also indicate that there are substantial differences in follicular renewal between adult human and rat ovaries. As part of this chapter, we present in detail protocols utilized to analyze oogenesis in humans and to study interspecies differences when compared to the ovaries of rat females.
Previous studies have reported controversial data on estrogen receptor (ER) expression in levator ani muscle. We investigated ER expression in levator ani muscle and fascia and compared it with the expression of progesterone receptor (PR) and androgen receptor (AR). The study included 55 women undergoing surgery for gynecological (asymptomatic, n = 10) or urogynecological conditions (symptomatic, n = 45). The asymptomatic and 21 of the symptomatic women received no hormone replacement therapy (HRT). The remaining 24 symptomatic women received some form of HRT. Biopsies were taken from the levator ani muscle and the overlying fascia, and quantitative measurements of immunohistochemical staining by image analysis were made. None of the levator ani muscle samples showed any evidence of nuclear ER expression in striated muscle fibers, but some cells in the muscular stroma did express ER. However, PR and AR expression was found in both muscle and stromal cells. Levator ani fascia showed nuclear ER, PR, and AR expression to varying degrees. There was a significant increase (p < 0.03) in ER expression in levator ani fascia of symptomatic patients without HRT when compared with asymptomatic age-matched women. The ER expression was significantly lower (p < 0.001) in postmenopausal symptomatic women receiving long-term estrogen replacement compared with age-matched women without HRT. Our data indicate that ER expression is significantly higher in symptomatic women compared with age-matched asymptomatic females. However, long-term estrogenization causes significant decrease of ER expression.
Background: Pelvic floor disorders affect almost 50% of aging women. An important role in the pelvic floor support belongs to the levator ani muscle. The p27/kip1 (p27) protein, multifunctional cyclin-dependent kinase inhibitor, shows changing expression in differentiating skeletal muscle cells during development, and relatively high levels of p27 RNA were detected in the normal human skeletal muscles.
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