C H A P T E R

11
Reproductive physiology of sheep (Ovis
aries) and goats (Capra aegagrus hircus)
Fuller W. Bazer
Department of Animal Science, Texas A&M University, College Station, TX, United States

O U T L I N E

Introduction 199 Estrous cycles and luteolysis 203

History of sheep 199 Pregnancy in does and ewes 205
Comparison of sheep with goats 199 Conceptus development in sheep during the
Puberty 200 peri-implantation period of pregnancy 206
Seasonal breeding 200 Pregnancy in ewes 207
Chorionic somatomammotropin
Reproductive tract anatomy 201
hormone 1 (CSH1) 208
Female reproductive tract 201
Parturition in ewes and goats 208
Reproductive tract anatomy of the ram
and buck 201 References 208
Estrous cycles of goats and ewes 203

Introduction civilizations allowed for spread of sheep raising

History of sheep
The exact line of descent between domestic
sheep and their wild ancestors is unclear, but
Ovis aries likely descended from the Asiatic
(Ovis orientalis) species domesticated by humans
between 11,000 and 9,000 BC for meat, milk and
skins, and wool.1 The Greeks and Romans relied
on sheep as primary livestock and those
to European colonists and then to the New
World from 1493 onwards.1
Comparison of sheep with goats2,3
Sheep and goats are closely related members
of the subfamily Caprinae. However, they are
separate species, so hybrids rarely occur and
are always infertile. Visual differences between

Animal Agriculture
https://doi.org/10.1016/B978-0-12-817052-6.00011-2 199 Copyright © 2020 Elsevier Inc. All rights reserved.
200 11. Reproductive physiology of sheep (Ovis aries) and goats
sheep and goats include the beard of goats and
divided upper lip of sheep. Sheep tails hang
down, even when docked, while short tails of
goats are held upwards. Many sheep breeds
are naturally polled, either in both sexes or just
in females, while naturally polled goats are
rare. Males of the two species differ in that
buck goats acquire a unique and strong odor
during the breeding season, but rams do not.
Sheep and goats have similar reproductive stra-
tegies and most breed in the fall months, but
some are can breed year-round.
Puberty2,3
Puberty is defined as when the individual be-
comes capable of reproduction (first ovulation in
the female and first spermatozoa in the ejaculate
of the male). In both male and female goats, pu-
berty may be reached without having achieved
adequate physical growth to support reproduc-
tion. In the doe, the first ovulation may not coin-
cide with first estrus, while in the buck ejaculate
quality and quantity may be insufficient to
achieve high fertility. In immature bucks, the
penis has adhesions that prevent it from being
fully extended, but the adhesions dissolve and
the penis can be fully extended at puberty. Goats
are generally “seasonally polyestrous,” and
exhibit estrous cycles during late summer, fall
and winter. The estrous cycle of goats is
20e21 days, with a range of 17e24 days. Does
are in estrus for approximately 30 h, and ovulate
33 h after the onset of estrus. Most goat breeds
are prolific, and mature females ovulate more
than one oocyte.
Ewes generally reach sexual maturity at
6e8 months of age, and rams generally at 4e6
months of age. There are exceptions. For
example, Finnish Landrace ewe lambs may reach
puberty as early as 3e4 months, and Merino
ewes sometimes reach puberty at 18e20 months.
Ewes have estrous cycles of about 17 days in
length and, during estrus, emit a pheromone in
urine indicating readiness to mate. A minority
III. Sheep and goat production
of rams (8% on average) display homosexuality
and a small number of the females born twin
to a male fetus in utero are freemartins that
may have an ovotestis and a poorly developed
reproductive tract, particularly the ovaries,
oviduct and uterus. These females are generally
sterile and exhibit masculine behavior.
Nutrition is among the most significant fac-
tors influencing reproductive development and
the onset of puberty. Inadequate nutrition delays
occurrence of the first estrus while a good state
of nutrition advances the age at the onset of
puberty. Season of birth also affects timing of
puberty in both does and bucks, with sensitivity
to changes in day length in effect during the
prenatal stages of development. Puberty in
spring-born kids may occur as early as in the
following fall breeding season. There is evidence
that the introduction of bucks or rams encour-
ages does and ewe lambs to reach puberty
earlier.
Seasonal breeding2,3
Differences exist in the onset and length of the
breeding season among the various breeds of
goats and sheep. Geographic location, particu-
larly degree of latitude, has a significant impact
on timing and length of the breeding season.
For example, tropical breeds of goats and sheep
may breed throughout the year depending on
factors such as rainfall, nutrition, and lactational
status. Onset of the breeding season includes
transitional periods during which gonadotropin
levels are increasing, but are not sufficient to
elicit estrus and ovulation. The onset of estrous
cycles can be hastened using management tech-
niques such as the introduction of males during
the transitional period. In billy goats, seasonal
breeding is associated with changes in testis
size and libido, and the development of a distinct
buck odor. In rams, those changes are not
observed, but the quality of semen generally im-
proves with onset of the breeding season during
cooler months of the year.
 Reproductive tract anatomy
Reproductive tract anatomy
Female reproductive tract4
The reproductive tract of mature ewes and
does includes several components. The ovaries
are the primary sex organ that produces oocytes
during ovulation and secrete female reproduc-
tive hormones (i.e., progesterone and estrogen).
The oviducts are the site of fertilization of
oocytes by sperm and they transport oocytes to
the site of fertilization at the junction of the
isthmus and ampulla and then transport
embryos into the uterus. The uterus is the site
of implantation of the blastocyst and then
placentation. Placentation involves establish-
ment of the chorioallantois for the exchange of
nutrients and gases required for growth and
development of the fetus, as well as the amnion
in which the embryo/fetus is located and sus-
pended in amniotic fluid. The collective term
for the embryo/fetus and its placental mem-
branes is conceptus. The uterus consists of two
uterine horns with a common uterine body.
The conceptus grows and develops in the uterus
during gestation. The uterus is closed to the
outside by the cervix, a canal consisting of
several cervical folds or rings. The most posterior
portion of the reproductive tract is the vagina
which is the site of semen deposition during
natural mating. The vagina also provides an
environment in which cells of the vagina and
mucus from cells of the cervix support the ease
of mating when the ewe or doe is in estrus and
it participates in transport of sperm toward the
oviduct following mating.
Reproductive tract anatomy of the ram
and buck4
The male reproductive tract has testes as the
primary sex organs to produce spermatozoa,
the male gametes, and sex hormones (i.e.,
testosterone and estrogen). Sperm production
III. Sheep and goat production
201
(spermatogenesis) takes place inside the seminif-
erous tubules and that process is supported by
Sertoli cells that form the blood-testis barrier
and also nourish cells involved in spermatogen-
esis. One population of spermatogonia undergo
mitosis to maintain a high number of cells with
the potential to differentiate into spermatozoa.
Selected spermatogonia are then recruited to
initiate spermatogenesis. The spermatogonia
initiate meiosis and move inside the blood-
testis barrier or adluminal compartment of sem-
iniferous tubules. The spermatogonia give rise to
primary spermatocytes, then secondary sper-
matocytes, spermatids and finally spermatozoa
with a 1N complement of chromosomes that
are released into the lumen of the seminiferous
tubules. The spermatozoa in the seminiferous tu-
bules are transported through tubules in the rete
testis to the vasa efferentia that eventually
coalesce to form a single duct, the duct of the
epididymis. The duct of the epididymis includes
the head (caput) and body (corpus) in which
spermiogenesis or maturation occurs, but this
is not completed until the sperm reach the tail
(cauda) of the epididymis. Spermatozoa pro-
duced by the testis enter the epididymis, also
located in the scrotum, which serves as the site
of sperm maturation (sperm acquire motility
and fertilizing capacity), and storage prior to
ejaculation. The vas deferens connects the
epididymis to the ampulla and accessory sex
glands which are the seminal vesicles, prostate
and bulbourethral glands. These accessory sex
glands are located in the pelvic region and pro-
vide the liquid portion of semen in which sperm
are suspended in the ejaculate. The Leydig cells
are in the interstitial tissue of the testes outside
the seminiferous tubules. Leydig cells synthesize
and secrete testosterone in response to luteiniz-
ing hormone (LH) from gonadotrophs in the
anterior pituitary gland. Testosterone from Ley-
dig cells is transported to Sertoli cells inside
the seminiferous tubules and Sertoli cells con-
vert testosterone to estradiol. Sertoli cells also
202 11. Reproductive physiology of sheep (Ovis aries) and goats
secrete inhibin that regulates secretion of follicle
stimulating hormone (FSH) from gonadotrophs
in the anterior pituitary gland.
As for the ovaries, testicular functions are
controlled by the gonadotropins LH and FSH,
as well as testosterone and estradiol. In contrast
to the female, where all ova are present at birth,
spermatozoa are produced through continuous
divisions throughout the reproductive life of
the male. In the final step of spermatogenesis,
cells develop the characteristics of the functional
spermatozoa (head, mid-piece and tail). Sperma-
tozoa are then released from the germinal epithe-
lium and pass to the epdididymis, where fluid is
removed and the sperm suspension is concen-
trated and stored in a dormant state prior to
ejaculation. There is considerable variation in
ejaculate volume and sperm concentration,
dependent on season, age, and sexual activity.
A normal range for volume of semen and con-
centration of sperm is 0.5e1.5 mL, and 1.5e5.0
billion sperm/mL.
The testes are located in the scrotum which
maintains the testes in an environment that is
3e5
C cooler than body temperature. Males
with testes retained in the abdomen, cryptor-
chids, are sterile due to impaired spermato-
genesis at body temperature, but cryptorchid
males may exhibit normal libido. Cooling of
the testes in the scrotum is accomplished by
four functional components of the testes. The
external cremaster muscle attaches to the pelvis
and contracts to bring the testes closer to the
body cavity in cold weather or in case of
fright/flight issues. This muscle can also relax
to allow the testes to drop away from the body
cavity to reduce exposure to body heat and dissi-
pate heat from the testes themselves. The pampi-
niform plexus includes the testicular artery
around which is coiled highly convoluted testic-
ular veins to which heat in arterial blood is trans-
ferred. The result is that the temperature of
arterial blood entering the testes at 39
C is
cooled to around 33
C at the base of the testes.
The third structure is the tunica dartos which is
III. Sheep and goat production
smooth muscle within the scrotum that contracts
during cold weather or flight/fright situations to
decrease surface area to pull testes closer to the
body and to decrease dissipation of heat from
the skin. Relaxation of the tunica dartos allows
for dissipation of heat from the testes. Finally,
as temperature increases there is a neural reflex
that stimulates sweating by the sweat glands in
the scrotum for evaporative cooling.
The accessory sex glands and external geni-
talia of rams and bucks requires that testosterone
be converted by the enzyme 5a-reductase to
dihydrotestosterone. The seminal vesicles pro-
duce and secrete a significant proportion of the
fluid in semen that is released into the vas defer-
ens during ejaculation. The seminal vesicles pro-
duce semenogelin, a protein that causes semen to
become sticky and jelly-like after ejaculation. In
addition, secretions from the seminal vesicles
contain proteins, enzymes, fructose, mucus,
vitamin C, flavins, phosphorylcholine and pros-
taglandins. Fructose is the hexose sugar that pro-
vides energy for the spermatozoa. The prostate
gland secretes a slightly alkaline fluid that is
milky or white in appearance and makes up a
portion of semen that is enriched in zinc and con-
tributes to the alkalinity of semen that helps
neutralize the acidity of the vaginal tract to pro-
long the lifespan of sperm. Prostatic fluid is
expelled in the first part of ejaculate, together
with most of the sperm and appears to ensure
that sperm have better motility, longer survival,
and better protection of genetic material. The
bulbourethral glands, also call Cowper’s glands,
contribute to the total volume of semen as a clear
fluid rich in mucoproteins that help to lubricate
the distal urethra and neutralize acidic urine
which remains in the urethra. There are some re-
ports that the bulbourethral gland fluid does not
contain sperm, but others have reported some
sperm into the pre-ejaculatory fluid. Never-
theless, the sperm source is a residual or pre-
ejaculatory leak from the testicles into the vas
deferens, rather than from the bulbourethral
gland itself.
 Reproductive tract anatomy
The penis is the final component of the male
reproductive tract and used to deliver semen
into the female. In the buck, erection is achieved
through extension of the sigmoid flexure that
allows an extension of up to 12 inches and by
filling of the cavernous tissues with blood. In
the non-erect state, the penis is contained in the
sheath.
Estrous cycles of goats and ewes2,3
The events of the estrous cycle are controlled
by hormones produced by the ovaries (estrogens
and progesterone) and the hypothalamic-
anterior pituitary-ovarian axis are essentially
the same for ewes and does. The hypothalamus
and anterior pituitary gland are located at the
base of the brain. The hypothalamus produces
gonadotrophin releasing hormone (GnRH) that
induces gonadotroph cells in the anterior pitui-
tary gland to release FSH that induces develop-
ment of ovarian follicles which contain an
ovum, and LH that induces ovulation of the
mature Graffian ovarian follicles. Further, LH in-
duces granulosa and theca cells of the ovarian
follicle to undergo luteinization and form a
corpus luteum (CL) that produces progesterone.
Progesterone is required for establishment and
maintenance of pregnancy. In addition to inter-
nal stimuli such as metabolic status, the
hypothalamic-anterior pituitary-ovarian axis is
also responsive to external stimuli including
changes in day length, nutritional status,
ambient temperature and the presence of males.
Follicles in the ovaries contain primary
oocytes (ova) and develop in successive waves
until some achieve dominance status and
ovulate to release secondary oocytes into the
infundibulum of the oviduct. Fertilization of
the oocyte occurs at the junction of the ampulla
and isthmus of the oviduct where sperm are pre-
sent. The follicle contains theca cells on the
outside of the basement membrane that produce
testosterone, while granulosa cells inside the
basement membrane of the follicle convert the
III. Sheep and goat production
203
testosterone to estrogens. After the ovulatory
surge of LH that induces ovulation, the theca
cells and granulosa cells transform into small
and large luteal cells, respectively to form the
CL and secrete progesterone. The CL secretes
progesterone, which prepares the uterus for
pregnancy, and suppresses the secretion of
GnRH, FSH and LH to prevent development of
mature Graffian follicles and ovulation during
either the luteal phase of the estrous cycle or
pregnancy.
Fertilization of the ovum occurs at the junc-
tion of the ampulla and isthmus in the oviduct
and requires the proper timing of insemination
and ovulation, as spermatozoa remain viable
for only 12 h in the female reproductive tract,
and the life span of the ovulated egg is
12e24 h. A healthy sperm will penetrate the
zona pellucida surrounding the egg using en-
zymes contained in the cap of the sperm head.
Fusion of the sperm cell with the egg will pre-
vent penetration of other spermatozoa. Fertilized
eggs move from the oviduct toward the uterus
and initiate cell divisions within 24 h. The devel-
oping embryo will continue to divide to reach
the blastocyst stage and remain free-floating
until it attaches to the uterine wall beginning
around Day 14 of gestation. The corpus luteum is
the primary source of progesterone throughout
gestation. The developing fetus is contained in
the placenta, a membrane that facilitates the ex-
change between the maternal and fetal vascular
systems at the maternal-conceptus interface.
While the placenta of sheep experiences the
most rapid growth between Days 20 and 90 of
gestation, fetal growth increases exponentially
between Day 90 and term (147 days of gestation)
or during the last trimester of pregnancy. Gesta-
tion length in the nanny and the ewe is approx-
imately 147 days.
Estrous cycles and luteolysis2,3
Sheep and goats, are spontaneously ovulat-
ing, seasonally polyestrous mammals with
204 11. Reproductive physiology of sheep (Ovis aries) and goats
recurring estrous cycles of 17 and 20 days for
does and 16e17 days for ewes. Ewes and does
are short-day breeders with regular estrous cy-
cles from late summer through mid-winter.
Sheep have been studied in greatest detail with
respect to endocrine regulation of the estrous cy-
cle and pregnancy; however, the basic mecha-
nisms for luteolysis and maternal recognition
of pregnancy are very similar for ewes and goats.
The endocrinology of recurring estrous cycles
and pregnancy in sheep and goats is well estab-
lished and is discussed with emphasis on hor-
monal signaling for maternal recognition of
pregnancy and the endocrinology of preg-
nancy.5,6 The estrous cycle of ewes and does is
uterine-dependent, because the uterus is the
source of prostaglandin F2a (PGF), the luteolytic
hormone responsible for functional and struc-
tural regression of the ovarian CL in the absence
of an appropriate maternal recognition of preg-
nancy signal. During the peri-implantation
period of pregnancy, the maternal recognition
of pregnancy signal from the conceptus in ewes
and does is interferon tau (IFNT). IFNT prevents
uterine release of luteolytic pulses of PGF. This
allows maintenance of one or more functional
CL for production of progesterone required for
the establishment and maintenance of preg-
nancy. Following successful signaling for
maternal recognition and establishment of preg-
nancy, progesterone from the CL and a number
of hormones from the placenta are required for
maintenance of pregnancy and birth of viable
offspring.
In ewes, Day 0 of estrus is designated as the
day of onset of sexual receptivity for mating
and the beginning of the estrous cycle. Estrus
lasts about 30 h and spontaneous ovulation oc-
curs about 30 h after onset of estrus in response
to an estrogen-induced ovulatory surge of LH
and FSH from the anterior pituitary at the onset
of estrus. Metestrus, Days 1e4 of the estrous cy-
cle, is characterized by luteinization of theca and
granulosa cells of the ovarian follicle under the
influence of LH to initially form the corpus
III. Sheep and goat production
hemorrhagicum (CH) and then the CL that se-
cretes progesterone. Diestrus, Days 4e14 of the
estrous cycle, is when the CL reaches its
maximum size and secretion of progesterone.
Near the end of diestrus, progesterone receptors
(PGRs) in uterine epithelia are down-regulated
by progesterone. In the absence of PGR and ef-
fects of progesterone, there is an increase in
expression of receptors for estrogen (ESR1) and
oxytocin (OXTR) necessary for oxytocin (OXT)-
induced secretion of luteolytic pulses of PGF
and luteolysis. Luteolysis is the regression of
the CL to an inactive structure called the corpus
albicans that is no longer functional in terms of
viable cells or their secretion of progesterone.
The onset of proestrus begins when the CL are
fully regressed and the ovarian follicles begin
producing significant amounts of estradiol-17b
(E2). A dominant follicle(s) is selected for ovula-
tion and onset of estrus marks the beginning of
the next estrous cycle.
The estrous cycle of ruminants is dependent
on the uterine endometrium for production of
luteolytic PGF. During diestrus, P4 increases
phospholipid stores and prostaglandin synthase
in uterine epithelia necessary for mobilization of
arachidonic acid by phospholipase A2 and its
conversion by prostaglandin synthase 2
(PTGS2) to PGF during late diestrus. Exposure
of the uterus to progesterone for 10e12 days
down-regulates PGR which, in turn, allows
ESR1 and OXTR expression by LE/sGE initially
and then GE and stromal cells. These are key
events in activation of the luteolytic mechanism
for endometrial production of luteolytic PGF.
Following up-regulation of ESR1 and OXTR, E2
induces phospholipase A2 to mobilize arachi-
donic acid for conversion to PGF and OXT is
released in a pulsatile manner from CL and pos-
terior pituitary to act via OXTR to induce pulsa-
tile release of luteolyic PGF that induces
regression of CL on Day 16. If ewes are hysterec-
tomized during the active life of the CL, luteoly-
sis does not occur because the uterus is the major
source of luteolytic PGF, and CL life span is
 Reproductive tract anatomy
prolonged to about 120e140 days, i.e., similar to
the duration of normal pregnancy.
Intimate intertwining of the uterine branch of
the ovarian vein and the ovarian artery allows
for the countercurrent exchange of luteolytic
PGF from the uterine venous drainage directly
to the ovarian artery for delivery to the CL for in-
duction of luteolysis. Luteolysis does not require
a decrease in LH receptors or withdrawal of
basal LH support from CL, but CL must be
exposed to five pulses of PGF over a 24 h period
to undergo complete luteolysis. Luteolytic pulses
of PGF on Days 15 and 16 in cyclic ewes are pre-
ceded by increases in circulating concentrations
of estradiol. Experimentally, administration of
estradiol to cyclic ewes on Day 9 or Day 10 of
the estrous cycle sequentially up-regulates
expression of ESR1 mRNA, ESR1 protein and
then OXTR mRNA and protein in endometrial
LE/sGE and then luteolysis occurs. Luteolytic ef-
fects of PGF on the CL have been attributed to:
(1) a decrease in luteal blood flow; (2) a reduction
in LH receptors; (3) uncoupling of LH receptor
(LHCGR) from adenyl cyclase; (4) activation of
protein kinase C; (5) influx of high levels of
calcium and/or; (6) activation of a cytotoxic
cascade. PGF may also act in concert with
endothelin to cause: (1) vasocontriction of blood
vessels to CL; (2) inhibition of expression of
LHCGR and steroid acute regulatory protein
(StAR) that inhibits P4 production; and (3)
recruitment of immune cells that produce cyto-
kines (interleukin 1 beta, tumor necrosis factor
alpha, interferon gamma) that stimulate produc-
tion of nitric oxide and apoptosis of luteal cells.
Pregnancy in does and ewes5,6
The antiluteolytic signal for maternal recogni-
tion of pregnancy in ruminants is IFNT pro-
duced by mononuclear trophectoderm cells of
conceptuses of all ruminant species. The effect
of IFNT in abrogating the uterine luteolytic
mechanism for maternal recognition of preg-
nancy signaling is similar, if not identical, for
III. Sheep and goat production
205
ewes, cows and does. IFNT, a Type I IFN,
secreted by trophectoderm of peri-implantation
ruminant conceptuses and has potent anti-
viral, antiproliferative and immunomodulatory
activities, as well as a unique role as the maternal
recognition of pregnancy signal in rumin-
ants. IFNT is produced in massive amounts
by conceptus trophectoderm as it undergoes
morphological transition from spherical to
tubular and filamentous forms during the peri-
implantation period of pregnancy, i.e., Days
10e21 in ewes. Secreted forms of ovine IFNT
are not glycosylated, whereas bovine IFNT is
glycosylated and caprine IFNT may be either
glycosylated or nonglycosylated. The structural
relatedness of IFNT of ruminants is based on ev-
idence that trophoblastic vesicles from sheep
extend the interestrous interval when placed
into the uterine lumen of cattle and ovine IFNT
suppresses OXT-induced secretion of PGF by
ovine, bovine and caprine uteri.
All Type I IFNs bind a common receptor
composed of two subunits, IFNAR1 and
IFNAR2, to induce cell signaling via the classical
Janus activated kinases (JAKs) and STAT1
pathway. However, several non-classical ISGs
are P4-induced and IFN-stimulated in ovine
uterine LE/sGE which lack both PGR and signal
transducer and activator of transcription 1
(STAT1). Therefore, the actions of progesterone
and IFNT may be through combined effects
of a progestamedin(s), e.g., fibroblast growth
factor 10 (FGF10) in sheep, and a non-classical
cell signaling pathway(s) for IFNT, such as
mitogen activated protein kinase (MAPK) and
phosphoinositide 3-kinase (PI3K) pathways to
affect gene expression and uterine receptivity
to implantation.5,6 Restriction of expression of
classical interferon stimulated genes by ovine
uterine luminal (LE) and superficial glandular
(sGE) epithelia is due, at least in part, to expres-
sion of interferon regulatory factor 2 (IRF2), a
potent transcriptional repressor, in those cells,
but IRF2 is not expressed in uterine GE and
stromal cells.
206 11. Reproductive physiology of sheep (Ovis aries) and goats
Caprine IFNT is secreted between Days 16
and 21 of gestation to prevent pulsatile release
of luteolytic PGF.5,6 Intra-uterine injections of
ovine IFNT in nanny goats extends CL lifespan.
Conceptus development in sheep during
the peri-implantation period of
pregnancy5,6
Sheep blastocysts are spherical on Days 4
(0.14 mm) and 10 (0.4 mm), elongate to the fila-
mentous form between Days 12 (1.0 by 33 mm)
and 15 (1 by 150e190 mm), and extend through
the uterine body into the contralateral uterine
horn by Days 16e17 of pregnancy. Secretion of
ovine IFNT begins on about Day 10 and in-
creases as conceptuses undergo morphological
changes from spherical (312 ng/mL uterine
flush) to tubular (1,380 ng) and filamentous
(4,455 ng) forms between Days 12 and 13 of
pregnancy. Successful transfer of conceptuses
to cyclic ewes can occur as late as Day 12, i.e.,
48e72 h prior to the luteolytic period. Thus,
IFNT acts to abrogate the uterine luteolytic
mechanism and prevent pulsatile release of
PGF. Intrauterine infusions of IFNT alone from
Day 11 to Day 15 of the estrous cycle prevents
luteolysis and extends CL lifespan. The antilu-
teolytic effects of IFNT are primarily on uterine
LE/sGE in ewes. IFNT silences transcription of
ESR1 and, therefore, ESR1-induced expression
of the OXTR gene in uterine LE/sGE to prevent
development of the endometrial luteolytic mech-
anism that requires pulsatile release of PGF.
However, basal production of PGF is actually
higher in pregnant than cyclic ewes due to
continued expression of prostaglandin synthase
2 (PTGS2) in the uterine LE/sGE. Further,
silencing ESR1 expression by IFNT prevents
estradiol acting via ESR1 from inducing PGR in
endometrial epithelia. The absence of PGR in
uterine epithelia is required for expression of a
unique set of P4-induced and IFNT-stimulated
genes in ovine uterine LE/sGE during early
III. Sheep and goat production
pregnancy. For most, if not all, actions of IFNT
on the uterus, P4 is the permissive hormone.
That is, uterine receptivity to implantation is
P4-dependent, but is preceded by loss of expres-
sion of PGR and ESR1 by uterine epithelia, and
the loss of PGR is a prerequisite for expression
of several ISGs in ewes. Thus, P4 likely acts on
PGR-positive stromal cells to increase expression
of a progestamedin(s) in ewes, likely FGF10, that
exerts paracrine effects on uterine epithelia and
conceptus trophectoderm that express its recep-
tor FGFR2IIIb. In sheep, classical ISGs (e.g.,
interferon stimulated gene 15, mouse myxovirus
resistance 1 and 20 , 50 oligoadenylate synthase)
are induced by IFNT only in uterine GE, stroma
and immune cells that do not express IRF2.
Because ovine uterine LE/sGE lack PGR and
STAT1, IFNT is unable to affect gene trans-
cription through the classical JAK-STAT1 cell
signaling pathway and must activate gene
transcription through alternate cell signaling
pathways such as MAPK and PI3K in uterine
LE/sGE.
Placental growth in ewes, measured as length
and weight, precedes rapid fetal growth. For
example, placental weight increases from 5 g
on Day 25e235 g on Day 70 or 5 g/day, whereas
the change from d 70 (235 g) to d 140 (348 g) av-
erages only 1.7 g/day. In contrast, average fetal
weight increases between Days 25 (0.2 g) and
70 (115 g) increased at about 2.5 g/day as
compared to the changes from Day 70 (115 g)
to Day 140 (2,956 g) that averages about 41 g/
day. Further, placental length is at 50% of its
final development at Day 25 (43 cm) compared
to Day 140 (75 cm) of gestation. Placental length
is influenced by the rapid elongation of the tro-
phectoderm during the peri-implantion period
between Days12 and d 25 of gestation.5
The increase in placental functions preceding
rapid fetal growth is associated with increases
in both vasodilation and angiogenesis in placen-
tomes of ewes as pregnancy advances.7 There is
also development of functional areolae respon-
sible for the transport of secretions from uterine
 Reproductive tract anatomy
glands across the placenta for release into the
fetal circulation.7e9 Secretions from uterine
glands are abundant and include serpins (also
known as uterine milk proteins), galectin-15,
stanniocalcin 1, gastrin releasing peptide, and
secreted phosphoprotein 1 (also known as osteo-
pontin) are produced in response to progester-
one and placental lactogen.10
The allantoic sac is a reservoir for fetal waste,
but more importantly a reservoir for nutrients.9
Transport of water into the allantois expands it
which, in turn, results in expansion of the
chorion and allantois to form the chorioallantoic
placenta.9 The volume of allantoic fluid increases
from Day 25 (21 mL) to Day 40 (91 mL), de-
creases to Day 70 (32 mL) and then increases
steadily to Day 140 (438 mL).
Volume and composition of amniotic fluid
change markedly during the course of gestation
in ewes. Amniotic fluid serves a number of
important roles. First, it buoys the fetus to allow
it to develop symmetrically in three dimensions.
Second, it prevents fetal skin from adhering to
the amnion. Third, the fetus drinks up to 1 L of
amniotic fluid in the last one-third of gestation
to gain water and other nutrients, including pro-
teins secreted by the lungs, salivary glands, and
amniotic membranes.9
Pregnancy in ewes
In sheep, establishment and maintenance of
pregnancy requires integration of endocrine
and paracrine signals from the ovary, conceptus,
and uterus.5,6,8 Sheep, goats and cattle have
synepitheliochorial (cotyledonary) placentae.
Implantation and placentation occurs between
Days 15 and 60 of pregnancy in ewes as the
uterus grows and remodels to accommodate
development and growth of the conceptus in
the last trimester of pregnancy. In addition, car-
uncles and cotyledons develop and interdigitate
to form placentomes which increase in vascu-
larity and the intercaruncular endometrial
glands grow substantially during pregnancy to
III. Sheep and goat production
207
secrete increasing amounts of histotroph that is
transported across the areolae of the chorioallan-
tois into the fetal-placental circulation. During
gestation, endometrial gland hyperplasia occurs
between Days 15 and 50 and then there is hyper-
trophy of the glands for maximal production of
histotroph after Day 60.
During this period, the pregnant ovine uterus
is exposed sequentially to estradiol, progester-
one, IFNT, placental lactogen (CSH1), and
placental GH that regulate endometrial gland
morphogenesis and differentiated functions.10
The binucleate cells of the chorion secrete
CSH1 from Day 16 of pregnancy which is coordi-
nate with initiation of expression of uterine milk
proteins (UTMP; serpin family of serine protease
inhibitors) and secreted phosphoprotein 1(SPP1
or osteopontin; an extracellular matrix protein)
that are excellent markers of endometrial GE dif-
ferentiation and secretory capacity. In maternal
serum, CSH1 is detectable by Day 18 and peaks
between Days 120 and 130 of gestation. It can
bind either homodimers of PRLR or hetero-
dimers of PRLR and GHR to transducer cell
signaling. In the ovine uterus, PRLR are
expressed specifically in uterine GE. Increasing
concentrations of CSH1 in maternal blood from
the placenta are associated hyperplasia and
hypertrophy of uterine GE, as well as their
increased production of UTMP, SPP1 and other
components of histotroph that support growth
and development of the conceptus.
Sequential exposure of the pregnant ovine
endometrium to E2, P4, IFNT, CSH1 and
placental GH constitutes a “servomechanism”
that activates and maintains endometrial remod-
eling, secretory function, and uterine growth
during gestation.10 The chronic effect of P4 is to
down-regulate epithelial PGR to allow expres-
sion of proteins by uterine GE, while CSH1 and
GH increase the number of endometrial glands
and levels of expression of genes encoding for
proteins such as UTMP and SPP1. The net effect
in ewes is a developmentally programmed
sequence of events, mediated by specific
208 11. Reproductive physiology of sheep (Ovis aries) and goats
paracrine-acting factors at the conceptus-
endometrial interface that stimulate both
intercaruncular endometrial remodeling and
differentiated function of uterine GE for
increased production of histotroph to support
fetal-placental growth.
Hormones from the anterior pituitary (prolac-
tin, PRL), ovary (progesterone) and placenta
(CSH1 and GH), as well as fetal adrenal (gluco-
corticoids) and pancreas (insulin) stimulate
mammogenesis, lactogenesis and uterine func-
tions that are required for conceptus develop-
ment in ruminants.10 Relaxin is not known to
have a role in parturition or mammogenesis in
ruminants.
Chorionic somatomammotropin hormone
1 (CSH1)
CSH1 is similar in structure and function to
growth hormone (GH1) and affects the meta-
bolic state of the mother during pregnancy to
facilitate transfer of nutrients to the conceptus.11
Temporal patterns of secretion of maternal CSH1
are similar during pregnancy for humans, sheep,
goats, rats, mice and cattle as concentrations in-
crease to peak values in the last trimester and
then decrease abruptly near the time of parturi-
tion. Except for cows, concentrations of CSH1
are higher in fetal than maternal blood and, in
all species, are positively related to amount of
placental tissue. Biological activities of CSH1
are mediated via homodimers of prolactin recep-
tors (PRLRs) and/or heterodimers of PRLR and
growth hormone receptors (GHRs) including
luteotrophic effects on CL in some species, stim-
ulation of fetal-placental growth, mammogene-
sis and lactogenesis. The luteotrophic effect of
CSH1 and PRL is established in rodents (mice
and rats). CSH1 is also involved in partitioning
of nutrients to support fetal development
through stimulation of amino acid uptake and
glyconeogenesis in fetal-placental tissues. CSH1
also stimulates lobulo-alveolar growth in mam-
mary glands through its mitogenic activity and
III. Sheep and goat production
stimulation of synthesis of milk proteins. CSH1
also decreases concentrations of urea nitrogen,
increases concentrations IGF1, nonesterified
fatty acids and glucose in serum, with little effect
on lipolysis, and it decreases maternal insulin
sensitivity to allow increased concentrations of
glucose in maternal serum and decreased utiliza-
tion of maternal glucose by maternal tissues
which favor transport of glucose and other nutri-
ents to the fetal circulation. In humans, CSH1
influences both fat and carbohydrate meta-
bolism and may contribute to the diabetogenic
state of women during pregnancy.
Parturition in ewes and goats
The endocrinology of parturition is very
similar for sheep, cattle and goats as described
in Chapter 3 of this book. For further information
on mechanisms for parturition in ruminant spe-
cies, please see the review by Whittle et al.12
Therefore, details on mechanisms for parturition
in sheep and goats will not be repeated in this
chapter.
References
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