Follicular dynamics throughout the oestrous cycle in sheep.

A review

M.-A. DRIANCOURT W. R. GIBSON L. P. CAHILL

Animal Research lnstitute, Weriibee, Vic. 3030, Australia.

) Monash University Clayton, Vic. 3168, Australia.
*
(

Summary. Whatever the stage of the cycle, follicles of various sizes are apparent on the
surface of the ovary of sheep. No evidence of waves of follicular growth at fixed-time
intervals has been found during the luteal phase, and growth probably occurs at random
until the follicle attains a size of 4 to 7 mm. This shows that follicles can enlarge under a
wide range of hormonal levels.
The recruitment of a crop of follicles, including the one which will ovulate, occurs at
variable times around luteolysis due to the interaction of endocrine and follicular factors
(FSH priming, sensitizing the follicle to increased LH pulsatility). All healthy fol-
licles > 2 mm in diameter are recruited. Selection of the follicle due to ovulate can be
defined by morphological criteria (size) or by its « killing » ability. In all cases, the timing of
follicle selection is highly variable, and it is due to this variability that the mechanisms of
selection are not fully known. They are presumably intraovarian, one of the follicles actively
inhibiting the growth of the others. The dominant follicle is probably maintained because of
its high oestradiol content, while the others undergo atresia.
The main feature of terminal follicular development is its flexibility in terms of hormonal
requirements, follicle size and the timing of the main events.

Introduction.

The ovary of adult ewes contains between 12 000 and 86 000 primordial
follicles and between 100 and 400 growing follicles, of which 10 to 40 are visible
on the surface of the ovary (Cahill, Mariana and Maul6on, 1979 ; McNatty et al.,
1982). In most sheep breeds, only one follicle ovulates at the end of each
oestrous cycle. The differentiation of a single preovulatory follicle is the result of a
complex interaction of the ovarian follicles and the hypothalamo-pituitary axis,
together with some intraovarian regulations. The aim of the present paper is to
describe the main events of follicular growth in single-ovulating ewes during the
oestrous cycle and the mechanisms governing these events. Observations on

) Present adress : Physiologie de

1
( la Reproduction, LN.R.A. Nouzilly, 37380 Monnaie, France, to
whom reprint requests should be sent.
other species are presented when they provide additional insight into the
observations on sheep ; women, monkeys and mares present long follicular
phases, and mares (Palmer and Driancourt, 1980) have been monitored in vitro by
ultrasonic echography to study most of preovulatory follicle enlargement. For
convenience, the 17-day oestrous cycle in ewes (day 0 oestrus) has been
=

divided into a luteal phase lasting from days 2 to 13 and a follicular phase lasting
from days 14 to 1.

Events of the luteal phase.

Steroid and gonadotrophin levels. -

Starting at day 3, the corpus luteum

(CL) secretes increasing quantities of progesterone until day 7, and the
concentration in peripheral plasma then remains at a plateau (1 to 3 ng/ml) until
day 12.
The pattern of LH concentration in the plasma during that plateau reveals
that LH is secreted in pulses at intervals varying with the breed and the stage of
the breeding season. Each pulse induces an increase in the concentrations of
oestradiol and androgens in ovarian vein plasma (Baird, Swanston and
Scaramuzzi, 1976). Wide fluctuations in FSH levels during this period occur from
day to day within animals and between animals (L’Hermite et al., 1972 ;
Salamonsen et al., 1973 ; McNeilly et al., 1976 ; Pant, Hopkinson and Fitzpatrick,
1977). The search for periodicity in these fluctuations, using autocorrelations, led
to the conclusion that waves of FSH do not occur at fixed-time intervals (Miller,
Nordheim and Ginther, 1981 ; Bister and Paquay, 1983). Depending on the
animal, these pulses occur at short intervals of from 3.5 to 6 days, at long
intervals of more than 10 days, or at both short and long intervals.
Follicular development - It is usually assumed that, for large follicles, waves
of follicular growth of 4-6 days duration occur during the luteal phase. This
assumption is based on : (1) the observation of fluctuations in the size of the
largest ovarian follicles of different animals on known days of the luteal phase.
Brand and De Jong (1973) claimed that two waves of follicular growth could be
detected during the luteal phase, one from days 1 to 10 and the other from day 6
to ovulation ; (2) studies of the fate of follicles marked by India ink at different
times of the cycle and followed over a period of a few days. Smeaton and
Robertson (1971) and Bherer, Matton and Dufour (1977) suggested that three
waves of follicles develop during the ewe cycle : on days 6 to 9 and 13 to 15 large
follicles were marked which did not ovulate, after day 15 they did ; (3) the
demonstration of peaks in oestradiol-170 secretion on days 3 and 4 (Cox, Mattner
and Thorburn, 1971), 6 to 9 and 11 to 15 (Mattner and Braden, 1972).
For several reasons, however, we must proceed cautiously before concluding
that waves of follicular growth exist in all animals at similar time intervals. Firstly,
authors do not agree on either the number of follicular waves or on the time they
occur. Secondly, the evidence for waves of follicular growth is weak since it has
never been statistically documented, and the use of different animals to estimate
the kinetics of follicular development is always open to criticism. Thirdly, it should
be recalled that steroidogenesis is hormonally regulated and that fluctuations in
steroid secretion might be due to fluctuations of gonadotrophin levels rather than
of follicular development. In addition, there is some experimental evidence, both
within and between animals, indicating a lack of follicular waves at regular
intervals. An analysis of the periodicity of FSH fluctuations (Miller, Nordheim and
Ginther, 1981 ; Bister and Paquay, 1983) did not demonstrate regularly occurring
4 to 6-day cycles in all animals. If follicular growth takes places in waves, FSH
might be expected to fluctuate regularly and evidence low levels during the
growth of a large follicle (due to oestrogen and inhibin secretions) and high levels
following atresia. Also, when the blocking effect of progesterone on the LH peak
is abolished by active immunization (French and Spennetta, 1981 ; Thomas et al.,
1983), leaving the ovary in a constant, artificial, follicular phase, there is a wide
variation in the intervals between ovulations (from less than 5 days to more than
15 days). Thirdly, if waves of follicular growth occur at fixed-time intervals, one
might expect a higher response to PMSG and a shorter interval between
prostaglandin-induced luteolysis and ovulation when the injections are given at
the time a wave has developed. This has never been confirmed ; the treatment of
ewes with PMSG on successive days of the late luteal phase has not shown any
difference between the days (Cumming and McDonald, 1967). The treatment of
mares with prostaglandins at a time of the luteal phase when they present large
follicles, has always resulted in a wide range of responses (Loy et al., 1979 ;
Driancourt, Palmer and Bour, 1983), indicating a lack of follicular wave
synchronism between animals during the luteal phase.
From the preceding considerations, it is highly possible that the growth of
the large follicles during the luteal phase in sheep occurs at random. The follicles
grow until they reach 4 to 6 mm and then regress. The number of such follicles
may vary considerably among individual animals. It is not known if the changes in
FSH secretion observed in some animals are linked to these random follicular
changes or to intrinsic hypothalamo-pituitary activity. The high follicular activity
found during the luteal phase in sheep, in which some follicles reach a size close
to preovulatory size (Brand and De Jong, 1973), suggests that preovulatory
enlargement can occur under a wide range of hormonal levels and pulse
frequencies. This high degree of follicular activity during the luteal phase is a
common feature in sheep, cows (Rajakoski, 1960) and saddle-type mares
(Driancourt, Palmer and Bour, 1983), but is seldom found in women (Gougeon,
1981) or pony mares (Driancourt, Mariana and Palmer, 1982).

Events of the follicular phase.

The differentiation of the ovulating follicle is a two-step process (Di Zerega
and Hodgen, 1981) in which the large antral follicles are brought forth from a pool
when exposed to sufficient gonadotrophin stimulation ; the development of such
follicles, which are candidates for ovulation, is called « recruitment ». Next, from
among these, a single follicle (in monotocous species) continues maturation,
ultimately being ovulated instead of degenerating ; this process is called
« selection » and, as a consequence, the selected follicle becomes « dominant ».
It is sometimes assumed that, at the time of recruitment, the ovulatory follicles
are already selected because they have some characteristics which seem to
indicate preselection (Tsonis et al., 1982). However, experimental elimination of a
part of the recruited follicle population by unilateral ovariectomy (Findlay and
Cumming, 1977), follicle cautery (Tsonis et al., 1982) or X-irradiation (Driancourt
and Mariana, 1982) during the early follicular phase never results in an increase in
the interval between luteolysis and ovulation in sheep. If the preselection
hypothesis was valid, an extended follicular phase would have been observed in
at least part of the animals due to the destruction of the follicle preselected for
ovulation.

Time-lag between recruitment and attainment of preovulatory size. -

Three
different types of experimental models have been used to study the duration of
the interval between recruitment and ovulation ; in all three, follicular growth was
prevented from proceeding to ovulation by the blocking effects on gonadotrophin
secretion of either a freshly ovulated follicle, a mature CL or seasonal anoestrus.
The results obtained using these three models were : if a recently ruptured follicle
was cauterized at the end of oestrus, a new follicle, able to generate another LH
peak, was present 48 h later (Smeaton and Robertson, 1971) ; when a mature CL
was induced to regress by a prostaglandin injection, the interval between the

injection and the beginning of the LH surge was 48 to 55 h (Acritopoulou et a/.,

1977) ; when ovulation was induced during seasonal anoestrus by administering
exogenous LH, the time-lag between the beginning of the treatment and the LH
peak was 30 to 50 h (McNatty et al., 1981a).
These results show that recruitment occurs around 48 h before the LH peak
and suggest that it probably coincides with luteolysis. This is different than in
rats, in which recruitment occurs at the time of the previous ovulation (Hirschfield
and Midgley, 1978), and in mares in which it takes place during the late luteal
phase (Driancourt, Palmer and Bour, 1983 ; Driancourt and Palmer, 1984), but it
is similar to what has been described in women (Nillson, Wikland and Hamberger,
1982) and monkeys (Goodman and Hodgen, 1979a, b) (fig. 11. However, defining
a mean time of recruitment might not be very meaningful since in species with a

long follicular phase, the time of recruitment varies considerably ; the interval
from recruitment to ovulation ranges from 8 to 21 days in pony mares (Driancourt
and Palmer, 1984) and from 12 to 20 days in monkeys (Goodman and Hodgen,
1979a, b). Recruitment is obviously a complex mechanism involving both
endocrine and ovarian factors.

Mechanisms involved in recruitment. - That prostaglandin F 2a is the

luteolytic factor inducing the regression of the CL has been convincingly
demonstrated by active (Scaramuzzi and Baird, 1976) and passive (Fairclough et
<> which results in the persistence of the CL.
a/., 1975) immunization against Pg F
2
In sheep, sufficient amounts of PG F 2. reach the ovary by day 13 via a counter-
current transfer between the utero-ovarian vein and the ovarian artery and/or via
the utero-ovarian lymphatics, to cause a decline in progesterone secretion. This
decline induces a marked increase in the frequency of LH pulses. The most
convincing evidence suggesting this has been obtained by determining the
consequences of premature withdrawal of progesterone, together with the
insertion of blank or progesterone-filled implants (Karsch et al., 1978). After
enucleation of the CL, pulsatile LH secretion increases, except if the luteal phase
levels of progesterone are maintained by progesterone-filled implants.
In contrast, no major change in FSH secretion has been found to coincide
with luteolysis (L’Hermite et al., 1972 ; Salamonsen et al., 1973 ; McNeilly et al.,
1976 ; Cahill et al., 19811.
Two questions may now be raised : how do these hormones and hormonal
changes trigger recruitment ? What follicles are recruited ?
Insight into the hormones involved in recruitment has been provided by
observations on anoestrous sheep and mares and on cyclic ewes treated with
follicular fluid.
The fact that preovulatory enlargement and ovulation can be induced during
anoestrus by the injection of LH or hCG, in amounts that produce plasma
concentrations mimicking those of the follicular phase of the cycle, points to LH
as a major hormone in recruitement (sheep : Goodman and Karsch, 1980 ;
McNatty et al., 1981a ; mares : Driancourt, Palmer and Bour, 1983). However,
several lines of evidence suggest that the follicles must be primed by FSH before
they are able to respond to LH. Firstly, in Ile-de-France ewes which present a
deep anoestrus, as well as in pony mares in deep anoestrus in January and
February, LH/hCG injections alone are unable to induce ovulation, whereas a
sequence of FSH and LH injections is effective (sheep : Oussaid, Cogni6 and
Poulin, 1982 ; mares : Driancourt, Palmer and Bour, 1983). Secondly, continuous
administration of regular pulses of LH during the anoestrous season is unable to
generate ovulation during the mid-anoestrous period (McNatty et al., 1984).
Thirdly, the administration of prostaglandin in combination with follicular fluid
(known to contain a substance that selectively decreases FSH levels) prevents the
recruitment of follicles over 3 mm and extends the oestrous cycle by a time similar
to (Miller et al., 1979) or longer than (Cummins, 1983) that of the duration of the
follicular fluid treatment. However, as follicular fluid contains numerous other
proteins (FSHBI : Fletcher et al., 1982 ; aromatizing inhibiting protein : Di Zerega
et al., 1983 ; atresia-inducing protein : Cahill, Clarke, Driancourt and Findlay,
unpublished data), the effect might not be linked to the depression of FSH levels
but to a direct action of the follicular fluid proteins on the ovary. Hence, it is very
likely that both FSH and LH are necessary for recruitment, the FSH priming being
needed to sensitize the follicles to LH. The magnitude of the FSH changes
required for this priming is still unknown.
Estimates of the lower size limit of the recruited follicles have been obtained
by four observations : (1) the study of the kinetics of individual follicle growth
followed in vivo by ink labelling showed that the follicle which ovulated was
recruited from those of any size > 2 mm at the time of natural (Driancourt, Cahill
and Bindon, 1985) or induced (Driancourt and Cahill, 1984) luteolysis (fig. 2) ;
(2) the destruction of follicles of different size classes by cautery did not
significantly delay ovulation, if some follicles > 2 mm (either 2 to 4 mm
or > 4 mm) were left untouched but ovulation was delayed when all the
follicles > 2 mm were cauterized ; (3) the number of follicles > 2 mm was
unchanged in cycles induced by prostaglandin injection alone (McNatty et al.,
1982) or in conjunction with PMSG (Dott et al., 1979) ; (4) while the induction of
ovulation in seasonal anoestrus by exogenous LH resulted in ovulation with a
time-lag similar to that occurring after luteolysis during cyclic activity, the size of
the largest follicles in anoestrous ovaries was around 3 mm (Smeaton and
Robertson, 1971 ; McNatty et al., 1981a). This strongly suggests that only
follicles > 2 mm in diameter are able to be recruited. That follicles < 2 mm are
little sensitive to recruitment agrees well with the observation that follicular
growth progresses to 2 mm in hypophysectomized ewes (Dufour, Cahill and
Maul6on, 1980).
An examination of the growth kinetics of individual follicles throughout the
follicular phase, using repeated laparotomy and ink labelling, suggests that all
healthy follicles > 2 mm are recruited (Driancourt and Cahill, 1984). The number
of such recruitable follicles seems to depend on the FSH levels in the 24 h
preceding luteolysis since ewes infused with FSH from 24 h before until 60 h after
induced luteolysis had a mean ovulation rate of 8 compared with an ovulation rate
of 3 for ewes in which infusion was started at luteolysis (Baird and Webb,
personal communication).
Appearance of a dominant follicle and atresia of the others. &horbar; As the
follicular phase progresses and the increasingly frequent LH pulses lead to the
recruitment of follicles > 2 mm, these follicles begin to secrete more oestrogen.
Despite the smaller amplitude of LH pulses (linked to oestrogen feedback :
Goodman et al., 19811, more oestradiol is secreted in response to each pulse than
at the earlier stages of the cycle (Baird, 1978). The repeated LH pulses induce
bursts of oestrogen secretion, and these summate to produce a rise in plasma
oestrogen concentration. These increased oestrogen levels have two effects :
they induce oestrous behaviour and they reduce FSH secretion since oestrogens
are a component of the negative feedback on FSH in sheep (Goodman, Pickover
and Karsch, 1981).
One of two sets of criteria is generally used to determine that the selection of
the ovulatory follicle has occurred : (1) the presence of a big follicle (monkeys :
Clark et al., 1979) secreting enough oestradiol to induce an asymmetry in the
concentrations of this steroid in ovarian blood (monkeys : Di Zerega et al., 1980 ;
sheep : McNatty et al., 1982) and binding LH on both the theca and granulosa
layers (monkeys : Di Zerega and Hodgen, 1980a ; sheep : Webb and England,
1982), or (2) the presence of a « killer » follicle which causes the other follicles to
degenerate, as shown by their decreasing size when followed by daily echography
(mares : Driancourt and Palmer, unpublished data), by the long time-interval
between ablation and ovulation (monkeys : Goodman and Hodgen, 1979a ;
mares : Driancourt and Palmer, 1984), or by the lack of a stimulatory effect of

exogenous gonadotrophins (monkeys : Di Zerega and Hodgen, 1980b ; mares :

Woods and Ginther, 1983). While in monkeys, the definition of selection by either
of the critera gives similar results, this is not true for mares since killing ability
appears often after selection according to size (fig. 3).
The data in sheep are not clear due to the shorter duration of the events of
the follicular phase. According to McNatty et a/. (1982), a dominant follicle (as
evidenced by asymmetrical ovarian secretion of oestradiol) is detectable as early
as 10 h after prostaglandin injection. This claim of early selection is difficult to
reconcile with the finding that unilateral ovariectomy performed before day 16 of
the cycle does not affect the ovulation rate (Findlay and Cumming, 1977),
suggesting that selection occurs only late in the follicular phase. In fact, defining
a mean selection time is probably meaningless since, whatever the criterion used,
a main feature of selection is that the time of its occurrence varies greatly, as
shown for mares on figure 3. This has also been demonstrated in sheep after ink
labelling of individual follicles. At 0, 4, 8, 12, 24 and 48 h after a prostaglandin
injection, the follicle ovulating at the following oestrus was the largest in 0/7, 1 /7,
1/7, 4/7, 5/7 and 5/7 ewes, respectively (Driancourt and Cahill, 1984). A similar
conclusion can be drawn from studies in monkeys (Clark et al., 1979 ; Di Zerega
et al., 1980). This variability makes it difficult to analyse mechanisms of selection
since, at a given time, selection may have occurred in some animals and not in
others, resulting in a mixture of the causes and consequences of selection.
The mechanisms by which a single follicle is selected while the others
undergo atresia are still unclear. In most cases (70 %), it is the largest healthy
follicle (i.e. growing when followed by ink labelling between days 13 and 15 of the
cycle) at the time of luteolysis which is selected (Driancourt, unpublished data).
However, the fact that this is not a general rule makes it necessary to postulate
that some follicles, even though large and healthy, may not be as competent as
others to complete preovulatory enlargement due to their improper morphological
(number and/or quality of granulosa cells) of functional (ability of granulosa cells
to divide or to differentiate gonadotrophin receptors) features.
The selection of a dominant follicle and the atresia of the others is usually
assumed to be due to decreasing FSH levels at that time. While the role of FSH
in atresia is well documented (Welschen and Dullaart, 1976), the factors
protecting one follicle from death are very unclear, since all the follicles are
bathed by similar concentrations. Two different hypotheses could explain this
selection. The first one, which could be called the hypothesis of « developmental
stability », suggests that when a follicle is big enough or has reached a given
stage of maturation, it manages to stay in a state of equilibrium. When it is in this
state, due to its morphological and functional features it does not respond to the
decreasing FSH levels which urge the other follicles on to atresia. Although there
is no evidence ruling out this hypothesis, numerous data show that the second
hypothesis, that of « active elimination », is more likely. According to this
hypothesis, selection would be an active process by which one follicle at a given
size and stage of maturation actively inhibits the growth of other follicles. Results
supporting this thesis have been obtained after gonadotrophin administration in
the presence or absence of a dominant follicle (monkeys : Di Zerega and Hodgen,
1980b ; women : Gougeon, Lef6vre and Testart, 1983). Furthermore, some
compounds possibly involved in this action have been detected in human follicular
fluid from the dominant follicle (Di Zerega et al., 1983), in the ovarian venous
blood draining that type of follicle (Di Zerega, Goebeismann and Nakamura, 1982)
and in ovine follicular fluid (Cahill, Clarke, Driancourt and Findlay, unpublished
data). Finally, active immunization against partially purified follicular fluid leads to
an increased ovulation rate, despite unaffected FSH levels, suggesting that the
antibodies raised by immunization are not against inhibin but rather against the
selection-inducing compound (O’Shea et al., 1983).
Whatever the mechanism of selection, it is bypassed when PMSG is injected.
As a result of selection, all the recruited follicles except one become atretic.
The factors implicated in further atresia have been described. The aromatizing
activity of early atretic follicles might be reduced either by a local mediator or by
greater follicle susceptibility to declining concentrations of FSH. The increasing
LH levels stimulate the production of androgens which are no longer converted to
oestrogens. Their accumulation and conversion to 5a-dihydrotestosterone leads
to a decrease in mitotic index (Hillier and Ross, 1979), a further decrease in
aromatase activity (Hillier et al., 1980), and a lowered sensitivity to gonado-
trophins (Farookhi, 1980), thus driving the follicle further towards atresia.
Together with this shift in steroid synthesis in sheep, the size of the atretic
follicles is reduced by 1.6 mm per day, a rate unaffected by the progression of
atresia (Driancourt and Cahill, 1984).
Maintenance of the dominant follicle. Once a dominant follicle appears, its
-

growth rate begins to decrease while atresia progresses in the unselected

follicles and recruitment is blocked (Driancourt and Cahill, 1984). A further
increase in its oestradiol secretion results in a peak of oestradiol concentration
around 40 to 50 h after an injection of prostaglandins (Baird, Swanston and
McNeilly, 1981). FSH levels decrease due to the increasing feedback of both
oestrogens and inhibin and, in spite of this, the dominant follicle remains healthy.
Maintenance of the dominant follicle can only be explained by the
« developmental stability» hypothesis. Three factors have been claimed to
contribute to this developmental stability : high intrafollicular FSH levels, high
blood flow, and the high oestradiol content of the dominant follicle. Neither of
the first two factors seems very plausible. Although it has been shown that a pool
of healthy large follicles has a higher follicular fluid content of FSH than a pool of
atretic ones (McNatty et al., 1981b), it has not been demonstrated that the
dominant follicle has a particularly high FSH level. Furthermore, the FSH
concentrations in preovulatory bovine follicles have been shown to be highly
variable (Dieleman et al., 1983). The data suggesting a role of blood flow in the
maintenance of the dominant follicle are also confusing. Firstly, the ligation of
one ovary, chronically reducing its blood supply, does not completely block
ovulation in that ovary (rats : Peppier, 1975 ; monkeys : Wehrenberg et al., 1979).
Secondly, measurement of the blood flow to individual follicles by the microsphere
technique has shown no difference between large follicles at the beginning of
oestrus (no dominant follicle) and those at late oestrus (Bruce and Moor, 1976).
However, morphological studies of the dominant follicle in monkeys have
demonstrated a higher density of blood vessels in its theca layer than in the other
follicles (Zeleznik, Schuler and Reichert, 1981).
In contrast, a role of intrafollicular oestradiol in maintaining the dominant
follicle can be postulated from observations showing that oestrogens sensitize
ovarian granulosa cells to gonadotrophins (Payne and Runser, 1958 ; Richards,
1975), possibly by triggering the differentiation of gonadotrophin receptors
(Richards, 1979).
What is striking, however, is that the developmental stability attained is very
fragile. Any decrease in the FSH levels produced by injecting oestrogens (Clark,
Dierschke and Wolf, 1981 ; Zeleznik, 1981) or anti-PMSG (Bindon and Piper,
1982) induces atresia of the dominant follicle in monkeys or reduces the ovulation
rate in superovulated ewes.

From the LH peak to ovulation. &horbar; In sheep, as in most species studied, there
is strong evidence that the preovulatory surges of LH and FSH that occur 50 to
60 h after a prostaglandin injection (Chamley et al., 1972 ; Baird, Swanston and
McNeilly, 1981) are provoked by a rise in oestrogen secretion in the preovulatory
follicle. In cyclic ewes, increases in oestrogen secretion always precede pre-
ovulatory LH surge (Chamley et al., 1972). Passive immunization of ewes against
oestradiol prevents the LH surge (Scaramuzzi, 1975). Oestradiol administration to
properly primed ovariectomized ewes provokes an LH surge (Pant, 1977). The
mechanisms triggering the LH peak are well documented. Both an increased
frequency of GnRH discharges and an increased sensitivity of the pituitary gland
to GnRH, induced by high oestradiol levels (Reeves, Arimura and Schally, 19711, ),
result in a rapid elevation of the LH levels as soon as the frequency of GnRH
discharges is high enough in relation to the half-life of LH to permit summation to
occur. Peaks of FSH and prolactin occur with the LH peak.
The preovulatory surge of LH initiates a sequence of changes in the
steroidogenesis of the dominant follicle and in its structure, as it prepares to expel
the oocyte.
At the time of ovulation, the plasma FSH concentration shows a rise that is
longer than the preovulatory elevation but which reaches the same peak levels.
There is no coincident rise in LH concentration or pulse frequency. The factors
causing the second FSH peak are not fully known ; it cannot be blocked by the
administration of pentobarbitone or antiserum to LH-RH (Dobson and Ward,
1977 ; Narayana and Dobson, 1979) or by the maintenance of high oestradiol
levels (Chappel and Barraciough, 1977), but is abolished by inhibin (Marder,
Channing and Schwartz, 1977 ; Schwartz and Channing, 1977) and passive
immunization against testosterone (Gay and Tomacari, 1974). While the role of
this second FSH peak has been demonstrated in the recruitment of a group of
follicles due to ovulate at the next cycle in rats (Chappel and Selker, 1979), its
function, if any, is unknown in sheep. Early claims that this peak triggers the
development of the follicles ovulating at the next cycle (Cahill et al., 1981) have
not been confirmed by further studies in which the peak was blocked by follicular
fluid, without any changes in the next ovulation (Cummins, 1983).
Conclusion.

What emerges from the present data is the flexibility of terminal follicular
growth. This is apparent (1) in the hormonal needs for preovulatory growth which
are similarly evidenced during the follicular and the luteal phases (2) in the size at
recruitment of the follicle which finally ovulates and (3) in the timing of the main
events of preovulatory follicle differentiation. A similar flexibility in the way prolific
sheep breeds generate a high ovulation rate has also been demonstrated in
Booroola ewes which show different mechanisms than Romanov ewes (Drian-
court et al., 1985 ; Driancourt, unpublished data). Any studies dealing with the
control of the mechanisms of preovulatory follicle enlargement will have to take
this flexibility into consideration.

Requ en février 1934.

A ccep t6 en juillet 1984.

Résumé. Croissance folliculaire terminale au cours du cycle chez la Brebis.

Chez la brebis, pendant tout le cycle, il existe des follicules visibles sur l’ovaire. Pen-
dant la phase lutéale, il n’existe pas de vagues de croissance folliculaire à intervalles régu-
liers mais plutôt une croissance au hasard de follicules qui atteignent 4 à 7 mm. Ceci
démontre que des follicules de taille presque préovulatoire peuvent se développer en pré-
sence de niveaux hormonaux très différents de ceux de la phase folliculaire.
Le recrutement d’un groupe de follicules parmi lequel se trouve celui qui ovulera se
produit à un moment variable mais centré sur la lutéolyse. Il résulte de l’interaction des
niveaux hormonaux et des caractéristiques des follicules (imprégnation des follicules par
FSH qui les sensibilise à l’augmentation de la fréquence des pulses de LH). Tous les follicu-
les sains excédant 2 mm de diamètre sont recrutés. Le moment de la sélection du follicule
qui ovulera peut être défini par des critères morphologiques (taille) ou par son aptitude à
induire la régression des autres follicules. Quel que soit le critère, le moment de la sélection
est très variable. Le mécanisme de sélection est probablement intraovarien, un des follicules
inhibant la croissance des autres. Le maintien du follicule dominant alors que les autres
régressent est probablement lié aux concentrations élevées en oestradiol qu’il contient.
La caractéristique principale du développement préovulatoire est sa flexibilité : 1) vis-à-
vis de ses besoins en hormones 2) quant à la taille des follicules impliqués 3) quant aux
moments où se produisent ses différentes étapes.

References

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Reproduction, Nutrition, Développement no 1A 1985. - 2