Pl. Nayudu et al., ABNORMAL IN-VITRO DEVELOPMENT OF OVARIAN FOLLICLES EXPLANTED FROM MICE EXPOSED TO TETRACHLORVINPHOS, Reproductive toxicology, 8(3), 1994, pp. 261-268
A system of mouse ovarian follicle culture in which follicles can be g
rown from a prenatal stage of development through antral formation has
been developed and modified recently by Nayudu and colleagues. Follic
les have been shown to grow in this culture system at a relatively con
stant rate and show responsiveness to LH at the end of the culture by
ovulation of mature oocytes. Reported here are the distinctly differen
t in vitro growth patterns of follicles explanted from 22- to 24-day-o
ld mice during a period when the colony was being treated for skin par
asites with tetrachlorvinphos (TCVP) (Rabond(R)). There is to date no
information on the effects of this compound on the mammalian female re
productive system. For follicles from the TCVP treated group, the dura
tion of growth as intact follicles was markedly reduced in comparison
to mice of the same strain and source not treated with TCVP. In the tr
eated group, premature termination of follicular growth was also assoc
iated with the spontaneous expulsion of oocytes with immature nuclei a
nd without cumulus cells. For those follicles from treated mice that d
id remain in culture until the day luteinizing hormone was given, the
ovulatory response was poor and the maturation response of the oocytes
was low in comparison with the follicles from untreated mice. The eff
ect of the treatment on the follicles was further characterized by obv
ious differences in the patterns of growth. Follicles in the untreated
group grew in a linear pattern at around 25 mum/day; a single phase,
fast pattern for the whole culture period. Follicles in the treated gr
oup showed a two-phase, slow-fast pattern, with growth in the first 48
h much slower than the untreated, and thereafter equal to or greater
than the untreated. From mice whose parents had been treated 2 to 4 mo
nths prior to the birth of the test mice, follicle growth (although im
proved) did not regain the linear growth pattern of the follicles from
the untreated group. Their growth was characterized by a three-phase,
fast-slow-fast Pattern, with a higher oocyte expulsion rate than the
untreated group. This association of in vivo TCVP application with pre
viously unobserved patterns of in vitro follicle development and decre
ased oocyte maturation capacity suggests that this chemical may have e
ffects on oocyte development and maturation in vivo. The results prese
nted here, if confirmed in a controlled study that includes assessment
of the effect of TCVP on in vivo fertility, suggest that our follicle
culture system may be a sensitive bioassay for the effects of environ
mental toxicants on oocyte development.