BIOLOGY OF REPRODUCTION 67, 1734–1740 (2002)
Published online before print 04 October 2002.
DOI 10.1095/biolreprod.101.002006
Effect of Maternal Exposure to the Environmental Estrogen, Octylphenol,
During Fetal and/or Postnatal Life on Onset of Puberty, Endocrine Status,
and Ovarian Follicular Dynamics in Ewe Lambs
C. Wright,2,3 A.C.O. Evans,2 N.P. Evans,4 P. Duffy,2 J. Fox,3 M.P. Boland,2 J.F. Roche,3 and T. Sweeney1,3
Faculties of Agriculture2 and Veterinary Medicine,3 Conway Institute for Biomolecular and Biomedical Research,
University College Dublin, Belfield, Dublin 4, Ireland
Department of Veterinary Preclinical Studies,4 University of Glasgow Veterinary School,
Glasgow G61 1QH, United Kingdom
ABSTRACT
Octylphenol (OP) is one of a number of compounds found
in the environment that has estrogen-mimicking actions in vivo.
Our objective was to determine if maternal exposure to octyl-
phenol during fetal and/or postnatal life would affect the onset
of puberty, endocrine status, and subsequent ovarian follicular
dynamics of ewe lambs. Lambs were born in March to ewes that
received twice weekly s.c. injections of octylphenol (1000 mg/
kg/day) from Day 70 of gestation to weaning (n 5 6); Day 70
of gestation to birth (n 5 3); birth to weaning (n 5 5; gestation
5 145 days); or corn oil from Day 70 of gestation to weaning
(control; n 5 5). Blood samples were collected twice weekly to
determine progesterone and FSH concentrations from 20 wk of
age throughout the first breeding season. Onset of puberty and
interestrous intervals were determined from 20 wk of age by
twice daily observation for estrus in the presence of a vasecto-
mized ram. During January the ovaries of each lamb were ex-
amined using transrectal ultrasonography from the day of estrus
for 15 days. Blood samples were collected every 8 h to examine
FSH concentrations and every 2 h to detect the preovulatory
gonadotropin surge throughout this estrous cycle. The onset of
puberty and first progesterone rise was advanced and the FSH
preovulatory surge was elevated for longer in the OP-treated
lambs compared with the control lambs (P , 0.05). Interestrous
intervals, FSH profiles, and ovarian follicular dynamics were not
affected (P . 0.05) by exposure to octylphenol. In conclusion,
octylphenol exposure advanced the onset of puberty but it did
not disrupt FSH concentrations or the dynamics of ovarian fol-
licular growth.
environment, follicle, follicle-stimulating hormone, ovulatory cy-
cle, puberty
INTRODUCTION
Widespread international concern has intensified over
the deleterious effects of endocrine disrupting compounds
(EDCs) found ubiquitously in the environment [1–5]. Pos-
sible human end points affected by EDCs may include an
increase in estrogen-sensitive cancers (breast and testicular)
[2, 6], declining sperm quality in men [7–10], a rise in
1
Correspondence: Torres Sweeney, Department of Animal Husbandry and
Production, Faculty of Veterinary Medicine, University College Dublin,
Belfield, Dublin 4, Ireland. FAX: 353 1 6600883;
e-mail: tsweeney@vetmed.ucd.ie
Received: 29 November 2001.
First decision: 27 December 2001.
Accepted: 28 May 2002.
Q 2002 by the Society for the Study of Reproduction, Inc.
ISSN: 0006-3363. http://www.biolreprod.org
1734
endometriosis [11], and precocious puberty in women [12,
13]. In addition, many chemicals released into the environ-
ment can disrupt normal endocrine and reproductive func-
tion in a variety of wildlife and domestic animals [14–18].
Estrogen is essential for growth and development of the
reproductive tract, regulation of estrous cyclicity, and the
development of secondary sex characteristics [19]. To elicit
these actions, estrogen binds to specific intracellular estro-
gen receptors. Chemicals found in the environment have
several mechanisms through which they may disrupt the
endocrine and reproductive systems. Chemicals such as al-
kylphenol polyethoxylates (APEOs) used in the manufac-
ture of detergents and pesticides are prevalent in the envi-
ronment as pollutants found in sewage and rivers [20, 21].
APEOs and their breakdown products, such as octylphenol
(OP), mimic steroid hormone action by competing with es-
tradiol and binding to estrogen receptors [20] and initiate
transcription of estrogen-receptor-regulated genes in vitro
[22–24]. OP can also stimulate estrogen receptor-mediated
physiologic responses in vivo [25, 26]. Although OP and
other EDCs may only be weakly estrogenic, they poten-
tially pose a threat to living organisms because of their
persistency and ability to bioaccumulate in adipose tissue
[27, 28].
Studies in rats have demonstrated that exposure to OP
disrupts puberty onset, estrous cycles, gonadotropin, and
steroid secretion [26, 29–31]. Recent studies in sheep, ex-
amining the effect of fetal exposure to OP, have identified
altered FSH concentrations [32] and folliculogenesis [33]
in newborn lambs. Our objective was to investigate the ef-
fects of exposure to the environmental estrogen OP during
fetal and/or postnatal life on the onset of puberty, endocrine
status, and ovarian follicular growth characteristics in ewe
lambs.
MATERIALS AND METHODS
Animals and Treatment
Nineteen Suffolk cross ewe lambs were born in March to ewes that
had received 1000 mg/kg of OP in twice weekly s.c. injections during
gestation and lactation. These ewe lambs were exposed to OP from Day
70 of gestation to weaning (treatment 1; n 5 6); Day 70 of gestation to
birth (treatment 2; n 5 3); birth to weaning (treatment 3; n 5 5); or corn
oil from Day 70 of gestation to weaning (treatment 4; n 5 5). The 4-(tert-
octyl)phenol ((CH3)3 CCH2C(CH3)2 C6H4OH) (Aldrich Chemical Com-
pany, Inc., Milwaukee, WI) had a purity value of 97%. It was dissolved
in corn oil on the day of application. The lambs were maintained outdoors
with their mothers and were weaned at 5 mo of age. At 6 mo of age the
animals were housed with free access to water and were each fed 0.45 kg/
day of 19% protein ration and 0.5 kg/day of hay. Animals were penned
according to treatment. All procedures were in accordance with the cruelty
 ENVIRONMENTAL ESTROGENS AND PUBERTY IN LAMBS
TABLE 1. Mean (6SEM) reproductive parameters and weight at puberty in ewes treated with octylphenol from Day 70 of gestation to weaning, Day
70 of gestation to birth, birth to weaning, or corn oil alone (control).a
Date of first
Date of first progesterone rise
Treatments estrus (date of year) (date of year)
D70–W (n 5 6) 29 Oct 6 9c 17 Oct 6 8c
D70–B (n 5 3) 29 Oct 6 2c 3 Oct 6 8c
B–W (n 5 5) 28 Oct 6 9c 17 Oct 6 6c
Control (n 5 5) 18 Nov 6 5b 16 Nov 6 9b
a D70, Day 70; W, weaning; B, birth.
b,c Values in columns with no common subscript are different (P , 0.05).
to animals act 1876 (European Community Directive 86/609/EC) licensed
by the Department of Health and Children, Ireland.
Endocrine Status and Ovarian Estrous Cycles Throughout
the First Breeding Season
Blood samples were collected twice weekly by jugular venepuncture
from 20 wk of age throughout the breeding season for FSH and proges-
terone analyses. Blood samples were stored at room temperature for 1 h,
placed in a refrigerator (48C) for 24 h, and centrifuged at 48C for 20 min.
The serum was decanted and stored at 2208C until required for assay.
First behavioral estrus (identified as the first date the female stood to
be mounted), interestrous interval, duration of estrus, and end of breeding
season were determined from 20 wk of age by twice daily observation of
ewes in the presence of a vasectomized ram. The end of the breeding
season was determined by transrectal scanning of the ovaries and 2 times
daily heat checking. Onset of puberty was defined as the first progesterone
rise (defined as the date the progesterone concentration first reached $0.4
ng/ml for two consecutive samples), followed by the first behavioral estrus.
The weight of each animal was recorded at 3-wk intervals.
Endocrine Status and Follicular Dynamics
To determine if pre- and/or postnatal exposure to OP had disrupted
folliculogenesis and/or endocrine status, hormone concentrations and fol-
licle growth patterns were monitored over 15 days during a synchronized
estrous cycle toward the end of the breeding season (January). A catheter
was inserted into the jugular vein of each ewe to facilitate collection of
blood. Throughout this period blood samples were taken every 8 h for
FSH concentration and blood samples were collected every 2 h (com-
menced 24 h postprostaglandin injection) to detect the preovulatory go-
nadotropin (FSH and LH) surge. A vasectomized ram was introduced into
the pen every 8 h to check for estrus activity.
Ovarian Function
Ovarian cycles were synchronized by two i.m. injections of Prosta-
glandin F2a (0.5 ml Estrumate) 24 h apart. Ovarian follicular activity was
studied for 15 days from estrus by transrectal ultrasonography. During
examination periods (5 min) the animals were housed in darkened con-
ditions and were restrained in a fostering crate. Scanning was conducted
using a rigid 7.5 MHz linear array transducer (Concept 500; Dynamic
Imaging Ltd., Livingston, Scotland) as previously described [34]. The
transducer was covered with a lubricant gel, inserted into the rectum, and
manipulated externally using the landmark of the bladder and uterine horns
to locate the ovaries. The position and diameter of each follicle $2 mm
in diameter and of each corpus luteum was recorded daily as previously
validated for ewes [35]. Individual follicles that reached 4 mm in diameter
and that were $3 mm for $3 days were retrospectively defined as iden-
tified follicles. Emergence was defined as the synchronous growth of a
cohort of identified and unidentified follicles, which were 2 or 3 mm in
diameter. The day of ovulation was determined by the collapse of the large
antral follicle and formation of a corpus luteum in its place and confirmed
by detection of estrus using a vasectomized ram.
RIA Analyses
Luteinizing hormone. Serum concentrations were determined by radio-
immunoassay using a modification of the method described by Sweeney
[35]. Briefly, on Day 1, 200-ml aliquots of serum or standard (NIDDK
oLH—AFP 9598B), 100 ml of monoclonal antibody (518B7 mcAby), and
100 ml of I125-labeled radioligand (NIDDK oLH—I—3 AFP 9598B) were
1735
Weight at End of breeding Interestrus
puberty (kg) season (date of year) interval (days)
45.4 6 1.5b 23 Jan 6 3b 16.2 6 0.2b
48.8 6 1.9b 29 Jan 6 2b 17.1 6 0.7b
48.0 6 1.7b 23 Jan 6 8b 17.8 6 1.0b
44.1 6 1.5b 25 Jan 6 5b 16.8 6 0.4b
added to tubes. The tubes were vortexed and incubated at room temper-
ature for 24 h. On Day 2, 50 ml of secondary antibody (donkey antimouse,
SAC-CELL, A-SAC 4, IDS, Boldon, Tyne and Wear, U.K.) was added to
the tubes, vortexed, and incubated for 30 min at room temperature. Dis-
tilled water (250 ml) was added and the tubes were centrifuged at 2500
rpm for 5 min. The supernatant was aspirated and the amount of radio-
activity in the pellet was determined using a gamma counter.
The sensitivity of the assay was 0.1 ng/ml with 95% binding. Inter-
assay coefficient of variations (CVs) at 0.3, 1.7, and 3.6 ng/ml (n 5 10)
were 9.3%, 9.7%, and 11.7%, respectively, and intraassay values were
27.6%, 14.8%, and 17.7%, respectively (n 5 6).
Follicle-stimulating hormone. The circulating concentrations of FSH
were measured in duplicate aliquots of plasma using an anti-ovine anti-
body (NIDDK oFSH AFP 5288113) and an iodinated antigen (NIDDK
oFSH–I–SIAFP–21 AFP 7571A), with a modification to the ovine stan-
dards (USDA–oFSH–SIAFP–RP–2) described by Evans et al. [36]. The
sensitivity of the assay defined by 95% binding was 0.06 ng/ml. Interassay
CVs for the three serum pools with values of 0.3, 1.3, and 3.4 ng/ml (n
5 15) were 15.2, 15.2, and 18.2%, respectively. Intraassay CVs were
28.85, 15.4, and 11.9%, respectively (n 5 6).
Progesterone. Serum progesterone concentrations were determined us-
ing a modification of the time resolved solid phase fluoroimmunoassay
DELFIA progesterone kit (EG&G Wallac, Turku, Finland) [34]. The stan-
dard supplied with the kit was replaced by progesterone (Sigma P0130)
standard, which was added to prepared progesterone-free ovine serum.
Interassay CVs at 0.2, 1.1, and 2.3 ng/ml (n 5 10) were 20.3%, 13.6%,
and 7.5%, respectively. Intraassay values were 14.8%, 5.78%, and 10.8%,
respectively (n 5 6).
Statistics
Differences in the onset of puberty; first progesterone rise; interestrous
interval; and body weight throughout the first breeding season and at the
onset of puberty, end, and duration of the breeding season were analyzed
using ANOVA (repeated measures where relevant) and Duncan t-test. The
onset of puberty data was further analyzed with body weight as a covariate
using the General Linear Models procedure of SAS (SAS version 6.12,
Cary, NC) [37]. Twice-weekly endocrine profiles, FSH, and progesterone
were analyzed by repeated-measures ANOVA using SAS.
Data from both ovaries were combined and the following parameters
were examined by ANOVA in SPSS, version 8.02 (Chicago, IL) [38]: The
number of waves; interwave interval; number of identified follicles per
wave; ovulatory and maximum follicle diameter; the total number of fol-
licles (small, medium, and large follicles combined); and the mean 8 hour-
ly FSH concentrations. The characteristics of the preovulatory gonadotro-
pin surges were compared across groups by ANOVA in SAS.
Before ANOVA, logarithmic transformations were carried out where
necessary to yield homogeneity of variance. All values are given as the
mean 6 SEM.
RESULTS
Animals exposed to OP had an earlier (P , 0.05) onset
of puberty in comparison to control animals, as determined
by the first progesterone rise and first behavioral estrus (Ta-
ble 1). In contrast, maternal exposure to OP had no effect
(P . 0.05) on the date at which the breeding season ended
in these animals (Table 1). All animals became anestrus at
a similar time, hence the duration of the breeding season
was shorter in control ewes (58 6 10 days) than in OP-
treated animals (85 6 7, 93 6 10, 86 6 9 days; P , 0.05).
1736 WRIGHT ET AL.

FIG. 1. Mean progesterone concentra-

tions during the 5 wk before and 2 wk af-
ter the first estrus in ewe lambs treated
with octylphenol from Day 70 of gestation
to weaning (open diamond: n 5 6), Day
70 to birth (open square: n 5 3), birth to
weaning (open triangle: n 5 5), or corn oil
(filled circle: control n 5 5).

Treatment with OP did not affect (P . 0.05) the interes-
trous interval (Table 1) or progesterone (5 wk before, 2 wk
after) concentration around the time of onset of puberty
(Fig. 1).
At the onset of puberty no differences were noted in
body weight between any of the OP-treated or control an-
imals (Table 1). The animals treated with OP were signif-
icantly heavier in November (Day 70 to weaning, 47 6 1.6
kg; Day 70 to birth, 49 6 1.9 kg; birth to weaning, 49 6
2.3 kg) and December (Day 70 to weaning, 49 6 1.7 kg;
Day 70 to birth, 51 6 1.0 kg; and birth to weaning, 49 6
2.3 kg) than the control ewes (41.4 6 1.4 kg and 42.9 6
1.5 kg, respectively; Fig. 2). However, there were no dif-
ferences (P . 0.05) among groups for animal weights in
October or January.
Gonadotropin secretion was monitored at 2-h intervals
around the time of the expected preovulatory surge during
the study. A FSH surge was only detected in one animal in
Day 70 of gestation to birth group (n 5 1), and as a result
this group was omitted from the analysis. No significant
differences were noted between groups in the amplitude of
the LH surge. However, when the FSH concentrations were
aligned relative to the peak LH preovulatory surge, FSH
was elevated for longer in control rather than OP-treated
animals (Fig. 3). In contrast, mean FSH concentrations as
assessed in twice-weekly blood samples prior to and during
the first breeding season and the mean FSH concentrations
across the study cycle were unaffected by treatment (P .
0.05; Table 2). Waves of ovarian follicle growth were noted
in all animals but no differences (P . 0.05) were seen
among groups in the proportion of ewes having two or three
follicle waves per cycles or the interval between waves
(Fig. 4). The mean number of identified follicles per wave,
the mean diameter of the ovulatory follicle, and the diam-
eter of the largest follicle were also unaffected by treatment
(P . 0.05). There were no differences (P . 0.05) detected
in the number of small, medium, or large follicles, or com-
bined numbers of follicles.
DISCUSSION
Advancing the onset of puberty without affecting inter-
estrous intervals, endocrine profiles throughout the first
breeding season, or ovarian follicular dynamics demon-
strates that OP did not exert a general overt effect, but
rather acted as a specific and discrete endocrine disrupter
at critical time periods during the development of ewe
lambs and the estrous cycle. The noted effects on puberty
mirror a trend in the human population where young girls
are developing pubertal characteristics at a significantly
younger age [39], and there is concern that this may be
partially due to exposure to EDCs. Advancement of puberty

FIG. 2. Schematic representation of the

correlation between onset of puberty and
weight for each group: the progeny of
ewes treated with octylphenol from Day
70 of gestation to weaning (open dia-
mond: n 5 6), Day 70 to birth (open
square: n 5 3), birth to weaning (open tri-
angle: n 5 5), or corn oil (filled circle:
control n 5 5). Each individual symbol
represents the date of onset of puberty of
an animal grouped by treatment. The lines
represent the mean body weight in each
group from October to January. Significant
differences in body weight observed in
November and December are indicated by
a star symbol.
 ENVIRONMENTAL ESTROGENS AND PUBERTY IN LAMBS 1737

FIG. 3. Mean (6SEM) FSH concentra-

tions in 2-h samples during the preovula-
tory surge in ewe lambs plotted aligned to
the peak of the LH surge: treated with oc-
tylphenol from Day 70 of gestation to
weaning (open diamond: n 5 6), birth to
weaning (open triangle: n 5 5), or corn oil
(filled circle: control n 5 4). A star identi-
fies significant differences in FSH concen-
trations among groups.

in rats exposed to chemicals with estrogenic action was
discovered 30 yr ago in a number of trials [40–42]. Our
data supports recent animal studies where pre- [43] and
postnatal exposure [29, 30] to various known endocrine dis-
rupters, including OP, advances the age of vaginal opening
in rats.
This study examined both the long-term changes in go-
nadotropin secretion (20–46 wk) and acute changes over
the course of an estrous cycle. No significant changes were
detected in mean FSH concentrations from 20 wk of age
or at 8-h intervals during the estrous cycle. However, when
FSH concentrations during the preovulatory gonadotropin
surge were aligned to the peak of the LH surge, suppression
in FSH concentrations was detected in OP-treated lambs
both before and after the surge. A similar differential effect
of OP on FSH and LH secretion has been described in male
and female lambs exposed during fetal life where maternal
exposure to OP suppressed FSH concentration without any
effect on LH [32]. Hence OP may induce effects on the
systems that regulate gonadotropin secretion, which result
in the observable effects in utero and at specific times dur-
ing the first year of life. There are conflicting reports on
the effects of environmental chemicals on endocrine pro-
files in males and females. Postnatal exposure to endocrine-
disrupting compounds (OP and pesticide) has been shown
to decrease or increase serum LH and FSH concentrations
in male rats and rams [44–46]. In female rats, postnatal and
adult exposure to xenoestrogen had a suppressive effect on
serum concentrations of LH, FSH, and progesterone [29,
47, 48].
There are varying reports on the effects of endocrine-
disrupting compounds on body weight. Laws et al. [29]
reported that none of the environmental estrogens examined
had any significant effects on body weight in rats exposed
as adults or during neonatal life, whereas Yoshida et al.
[31] reported that female adult rats exposed to high doses
of OP showed a significant suppression of body weight.
However, our results support the findings of Howedshell et
al. [43] who found that exposure to an EDC increased post-
natal body weight and advanced puberty in female mice.
Therefore, from these results we can suggest that OP may
be exerting an anabolic estrogenic effect promoting growth
in sheep.
It is recognized that neither the gonad nor the anterior
pituitary of the immature sheep limit sexual development
[49–51], and a previous study has demonstrated that deliv-
ery of exogenous GnRH during neonatal life was effective
in inducing precocious puberty in ewe lambs. The pituitary
LH release system in prepubertal ewe lambs is capable of
responding when exposed to exogenous estradiol [52, 53].
Nass et al. [53] discovered altered reproductive function
and gonadotropin response in rats treated with estrogen be-
fore puberty and hypothesized that it was due to an alter-
ation in hypothalamic GnRH release [51]. In addition, es-
trogenic mimics present in the environment can disrupt hy-
pothalamic control of pituitary-ovarian function in the rat
[47, 54]. Combining the information from these studies and
our results, we hypothesize that exogenous treatment with
OP may have altered GnRH secretory patterns by advanc-
ing the lambs’ sensitivity to the stimulatory effects of es-
tradiol.
Development of the full complement of oocytes avail-

TABLE 2. Mean (6SEM) ovarian follicular dynamics and FSH concentrations during 15 days from estrus in ewes treated with octylphenol from Day
70 of gestation to weaning, Day 70 of gestation to birth, birth to weaning, or corn oil alone (control). There were no significant differences (P . 0.05)
among groups.a

Number of Ovulatory Total number

Number of Interwave identified follicles/ follicle Max follicle of follicles
Treatment waves (number) interval (days) wave (mm) diameter (mm) diameter (mm) (follicles per day) FSH (ng/ml)
D70–W (n 5 6) 2.8 6 0.3 5.6 6 1.2 1.6 6 0.1 6.3 6 0.4 6.0 6 0.0 4.5 6 0.2 1.1 6 0.1
D70–B (n 5 3) 2.3 6 0.3 8.2 6 1.8 1.7 6 0.4 6.0 6 0.0 5.7 6 0.7 4.1 6 0.5 1.2 6 0.1
B–W (n 5 5) 2.8 6 0.2 5.1 6 1.0 1.6 6 0.1 6.3 6 0.4 6.4 6 0.2 4.4 6 0.2 0.8 6 0.1
Control (n 5 5) 2.4 6 0.2 5.7 6 0.9 1.3 6 0.1 6.2 6 0.3 5.4 6 0.2 4.6 6 0.5 1.3 6 0.2
a D70, Day 70; W, weaning; B, birth.
1738 WRIGHT ET AL.

FIG. 4. Growth patterns of identified

ovarian follicles in wave 1 (filled circle),
wave 2 (filled triangle), and wave 3 (filled
square) in individual animals treated from
Day 70 of gestation to weaning (A and E,
n 5 6); Day 70 of gestation to birth (B
and F, n 5 3); birth to weaning (C and G,
n 5 5); or corn oil (D and H, control n 5
5). A–D) Animals with two follicle waves
per cycle; E–H) animals with three follicle
waves per ovarian estrous cycle. Mean
(6SEM) FSH (filled diamonds) concentra-
tions in 8-h samples are located at the
lower portion of the graph. Arrows indi-
cate time of ovulation.

able in adult life occurs during fetal development in the
sheep under the influence of high concentrations of FSH
between Days 100 and 130 of gestation [55]. Exposure to
OP during this critical period of development has been
shown to alter adult follicle populations and promote early
follicle growth in sheep [33]. We therefore hypothesized
that the earlier onset of puberty may be associated with a
disruption in the characteristics of follicle development.
Studies in rats have demonstrated that postnatal exposure
to a range of environmental estrogens can disrupt estrous
cyclicity [29, 31, 44, 53, 56] and block ovulation [49]. En-
docrine disrupters could affect follicle wave dynamics by
altering steroid receptor function [29] or hypothalamic
GnRH release [53]. In contrast, the data in the present study
suggest that exposure to OP during fetal and/or postnatal
life does not have any adverse effect on follicle wave dy-
namics toward the end of the first breeding season. All ewes
had two to three waves of follicle growth during an estrous
cycle, which is in agreement with previous studies [34, 57,
58]. In addition, the duration of estrus of ewes in this trial
was normal according to the classic study of McKinszie
and Terrill [58].
OP altered physiological processes by advancing the on-
set of puberty and first progesterone rise, yet once the ewes
reached puberty the xenoestrogen appeared to no longer
exert a disrupting effect and the ewes underwent normal
follicle wave development. This pattern is not without pre-
cedence as neonatal exposure of male rats to OP has been
shown to advance aspects of pubertal spermatogenesis [59]
and disrupt development of excurrent ducts in the testis
[60], but by adulthood these effects were no longer evident.
There are two possible explanations for this. First, Stoker
et al. [54] has shown that continued exposure to a xenoes-
trogen is without apparent effect on female reproductive
 ENVIRONMENTAL ESTROGENS AND PUBERTY IN LAMBS
capacity, indicating that the female may become tolerant to
such adverse effects. Second, effects of chronic exposure
may not be obvious until the offspring is well into adult-
hood. Data by Picton et al. [33] would suggest that if the
ewe lambs in this study were maintained until later in adult
life they may have had a shorter reproductive life span. The
reproductive consequences of advancing puberty seen in
this study raises a serious health concern, as evidence is
available that suggests that women who attain puberty at
significantly earlier ages are at greater risk of developing
breast cancer in later life [12].
In conclusion, maternal exposure to OP during pre- and/
or postnatal life advanced the onset of puberty and first
progesterone rise but did not disrupt the interestrous inter-
val or endocrine profiles throughout the first breeding sea-
son or the pattern of ovarian follicular dynamics.
ACKNOWLEDGMENTS
We thank Tony Harte, Pat Brophy, Gerry Connellan, and the staff at
Lyons for their assistance and maintenance of animals throughout the trial.
They also wish to thank Denis Flynn, Liz Lane, Jose Maria Lozano, Fa-
bian Ward, Brian Enright, and David Nation for their assistance during the
experiment. We are also grateful to Niamh Hynes and staff at the Animal
Husbandry and Production laboratories for assisting with hormone assays.
We would like to express our thanks to A.F. Parlow (NIDDK National
Hormone and Pituitary Programme) and J.F. Roser, University of Califor-
nia, Los Angeles (UCLA), for their gifts of hormone preparations. Further
thanks to John Dardis and Sylvie Snjieders for their statistical assistance.
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