|
|
- 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.
-
-
- Colborn T
- Environ Health Perspect 1995 Oct 103 Suppl 7 135-6
-
-
- 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
-
-
- 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.
|
