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Environmental Oestrogens and Fertility
Are oestrogens involved in falling sperm counts and disorders of
the male reproductive tract?
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Sharpe RM,
Skakkebaek NE
Lancet
1993 May 29 341:8857 1392-5
Abstract
The
incidence of disorders of development of the male reproductive tract
has more than doubled in the past 30-50 years while sperm counts have
declined by about half. Similar abnormalities occur in the sons of
women exposed to diethylstilbestrol (DES) during pregnancy and can be
induced in animals by brief exposure to exogenous oestrogen/DES during
pregnancy. We argue that the increasing incidence of reproductive
abnormalities in the human male may be related to increased oestrogen
exposure in utero, and identify mechanisms by which this exposure could
occur.
Environmental
estrogens: health implications for humans and wildlife.
Colborn
T
Environ
Health Perspect 1995 Oct 103 Suppl 7 135-6
Endocrine
Screening Methods Workshop report: detection of estrogenic and
androgenic hormonal and antihormonal activity for chemicals that act
via receptor or steroidogenic enzyme mechanisms.
Gray LE Jr,
Kelce WR, Wiese T, Tyl R, Gaido K, Cook J, Klinefelter G, Desaulniers
D, Wilson E, Zacharewski T, Waller C, Foster P, Laskey J, Reel J, Giesy
J, Laws S, McLachlan J, Breslin W, Cooper R, Di Giulio R, Johnson R,
Purdy R, Mihaich E, Safe S, Colborn T, et al
Reprod
Toxicol 1997 Sep-Oct 11:5 719-50
Odd
chromosome movement and inaccurate chromosome distribution in mitosis
and meiosis after treatment with protein kinase inhibitors.
Nicklas RB,
Krawitz LE, Ward SC
J Cell
Sci 1993 Apr 104 ( Pt 4) 961-73
Abstract
Errors in
chromosome orientation in mitosis and meiosis are inevitable, but
normally they are quickly corrected. We find that such errors usually
are not corrected in cells treated with protein kinase inhibitors.
Highly inaccurate chromosome distribution is the result. When
grasshopper spermatocytes were treated with the kinase inhibitor
6-dimethylaminopurine (DMAP), 84% of maloriented chromosomes failed to
reorient; in anaphase, both partner chromosomes were distributed to the
same daughter cell. These chromosomes were observed for a total of over
60 h, and not a single reorientation was seen. In contrast, in
untreated cells, maloriented chromosomes invariably reoriented, and
quickly: in 10 min, on average. A second protein kinase inhibitor,
genistein, had exactly the same effect as DMAP. DMAP affected PtK1
cells in mitosis as it did spermatocytes in meiosis: improper
chromosome orientations persisted, leading to frequent errors in
distribution. We micromanipulated chromosomes in spermatocytes treated
with DMAP to learn why maloriented chromosomes often fail to reorient.
Reorientation requires the loss of improper microtubule attachments and
the acquisition of new, properly directed kinetochore microtubules.
Micromanipulation experiments disclose that neither the loss of old nor
the acquisition of new microtubules is sufficiently affected by DMAP to
account for the indefinite persistence of malorientations. Drug
treatment causes a novel form of chromosome movement in which one
kinetochore moves toward another kinetochore. Two kinetochores in the
same chromosome or in different chromosomes can participate, producing
varied, dance-like movements executed by one or two chromosomes. These
kinetochore-kinetochore interactions evidently are at the expense of
kinetochore-spindle interactions. We propose that malorientations
persist in treated cells because the kinetochores have numerous, short
microtubules with a free end that can be captured by a second
kinetochore. Kinetochores capture each other's kinetochore
microtubules, leaving too few sites available for the efficient capture
of spindle microtubules. Since the efficient capture of spindle
microtubules is essential for the correction of errors, failure of
capture allows malorientations to persist. Whether the effects of DMAP
actually are due to protein kinase inhibition remains to be seen. In
any case, DMAP reveals interactions of one kinetochore with another,
which, though ordinarily suppressed, have implications for normal
mitosis.
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