Biologic Markers in Reproductive Toxicology (1989) / Chapter Skim
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11. Introduction
11. Introduction
Pages 149-162
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From page 149... ...
as an assessment of fecundity in women. The introductory material is followed by four chapters that discuss biologic markers of germ cell damage; development and aging; cyclic ovarian function; and conception, implantation, and early embryonic loss.
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From page 150... ...
Third, exposures or physiologic deterioration sustained during the long resting phase of oocyte maturation may account for the increased sensitivity of female germ cells to meiotic errors, such as nondisjunction. Whether a blood/follicle barrier exists to protect the oocyte from toxic substances is controversial, and more research on this question is needed.
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From page 151... ...
Whether prenatal exposure to DES also alters the hypothalamus or pituitary is being investigated (for example, in a study of sexual activity and functioning in DES daughters (Meyer-Bahlburget al., 1985~. MATURATION Hormonal Changes Assumption of adult female reproductive function involves major increases in ovarian and adrenal production of steroids that induce maturation of cells that are responsive to sex steroids.
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From page 152... ...
i' , ~ ~ Increased / release of LRF 1 1 1 Increased pituitary responsiveness to LRF Rising gonadotropin levels Increased gonadal responsiveness to gonadotropins Rising sex steroid levels Sleep associated increase in LH secretion: episodic secretion of LH 1 '\1 Activation of positive feedback mechanisms I : I Fetus Infancy and childhood Puberty Adult FIGURE 11-3 Schematic illustration of development of hypothalami~pituita~y-gonadotropin-gonadal interrelationship In relation to onset of puberty. From Grumback et al., 1974.
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From page 153... ...
Exposure of neonatal rats to DDT causes major changes in neuroendocrine functions, including early puberty and a syndrome of delayed-onset, persistent estrus in association with a polyfollicular ovarian status (Heinrichs et al., 1971~. This permanent reproductive impairment in female rodents resembles the neonatal masculinization of the hypothalamus and the polyfollicular, anovulatory ovarian syndrome caused by exogenous steroids (Gorski, 1971; Mobbs et al., 1984~.
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From page 154... ...
On adult reproductive functions that can be manifested at puberty or can induce precocious cessation of fertile cycles (delayed anovulatory syndrome)
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From page 155... ...
The primary oocyte is surrounded by a single layer of cells-presumably forerunners of granulosa cells-and little is known of the physiology of early follicular development. Only the final 14 days of follicular maturation appear to be influenced cyclically by gonadotropins in primates.
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From page 156... ...
Note that development on cupies three full cycles. Parameters include size of developing follicles measured by ultrasound or during laparoscopy, gonadotropin concentrations in serum; estrogen and progestogen concentrations in serum, saliva, and urine; ratio of urinary steroids; state of endometrial proliferation; relative cervical mucus volume; and basal body temperature.
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From page 157... ...
Paradoxically, a sustained estrogen content for approximately 24-36 hours has a positive feedback effect and results in a surge of both gonadotropins. That causes a series of events within the follicle, including intrafollicular prostaglandin synthesis, terminal oocyte maturation, a shift in steroidogenesis from estrogen to progesterone by the granulosa cells, morphologic luteinization, and, ultimately, rupture of the follicle and release of the oocyte with its investment of cumulus cells into the peritoneal cavity (LeMaire et al., 1973~.
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From page 158... ...
More detailed hormonal studies over some period are required. Effects of exposure to toxicants on cyclic ovarian function have not been investigated widely, but several observations FEMALE REPRODUCTIVE TOXICOLOGY suggest that occurrence of menses is sensitive to environmental influences.
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From page 159... ...
Decreasing fertility (ability to produce offspring) is a hallmark of approaching menopause and follows remarkably similar trends in modern populations of industrial countries, as well as in groups, such as the Hutterites, that try to maximize fertility and live offspring (Fig.
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From page 160... ...
Ovarian steroids have some effect on postmenopausal osteoporosis; oophorectomy in young women can precipitate premature bone loss, and steroid therapy appears to reduce the risk of age-related fractures. However, inasmuch as bone loss begins about 10 years before measurable deficits in blood estrogens, other factors that do not depend directly on changes in blood estrogen concentrations must also be involved.
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From page 161... ...
Toxic environmental estrogens are important, because they resemble some aspects of reproductive senescence. Sheep fed on phytoestrogen-containing clovers develop a permanent infertility syndrome 161 FIGURE 11-8 Loss of ovarian oopytes during aging In the mouse and human.
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