- Stages of the sexual cycle
- Main hormones
- Action of the hormones on uterus
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THE SEXUAL CYCLE OF THE BITCH
2 cycles per yearthe cycles are identic even if pregnancy or not
4 stages rhythm by the sexual hormonesproœstrusœstrusmétœstrus = postoestrusanœstrus
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STAGES OF THE SEXUAL CYCLE
Heat
Sexual inactivityPregnancy or not
ovary
folliculeovule
Estrogens ’ secretion
Prooestrus
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THE SEXUAL CYCLE : OVARIAN LEVEL
ovulation
Estrogens ’ secretion
Transformation of follicule intocorpus luteum
Secretion of progestérone
Proœstrus Oestrus
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THE SEXUAL CYCLE : OVARIAN LEVEL
corpus luteum
Secretion of progestérone
Proœstrus Oestrus Metœstrus
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THE SEXUAL CYCLE : OVARIAN LEVEL
Disappearanceof the corpus
luteum
Progressive degeneration[pseudopregnancy]
Rapide lysis through Prostag. [parturition]
Proœstrus Oestrus Metœstrus Anœstrus
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THE SEXUAL CYCLE : OVARIAN LEVEL
Proœstrus Oestrus Metœstrus Anœstrus
Sexualinactivity
15-20 days 2 months 3,5 months
HeatPregnancy
or Pseudopregnancy
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THE SEXUAL CYCLE : OVARIAN LEVEL
10
PROOESTRUS
Progesterone ng/ml
oestradiol pg/ml
OESTRUS ANOESTRUSMETOESTRUS
D 63
Brutal drop beforeparturition
Fertilization Implantation : D 22
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MAIN SEXUAL HORMONES
Precocious abortion Late abortion
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MAIN SEXUAL HORMONES
PROOESTRUS
10
Progesterone ng/ml
oestradiol pg/ml
ANOESTRUS
Progressive drop if absence of pregnancy
OESTRUS METOESTRUS
D 63
10
Progesterone ng/ml
oestradiolpg/ml
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MAIN SEXUAL HORMONES
The hormonal profile is identical if the bitch is pregnant or not
Beginning of proœstrus
Thin uterine mucosa, without folds
Opening of cervix
Estrogens
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ACTION OF THE HORMONES ON UTERUS
Preparation of the uterine mucosa
Open cervixUpflow of germs
Estrogens
Synthesis of progesterone
receptors
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Oestrus
ACTION OF THE HORMONES ON UTERUS
Ovulation
: Progesterone receptor
Upflow of germs
Blood flow + severalleukocytes
prevent the bacterialcontaminations
Estrogens
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Oestrus
ACTION OF THE HORMONES ON UTERUS
. Uterine milk
Closed cervix
. Important development of the uterinemucosa
progesterone
Development of the egg if Fertilization
: Progesterone receptors
Control of musculature
Regulation of defenses
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Metoestrus
ACTION OF THE HORMONES ON UTERUS
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Progesterone
ACTION OF THE HORMONES ON UTERUS
•Prepare the uterine matrix
•Close the cervix
•Inhibit the contractions of uterine musculature
•Regulate the immunitary defenses
It creates propitious conditions for the physiological life or pathological development in
the uterine lumen
Placenta
Closed cervix
Foetalampulla
progesterone
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Metoestrus with pregnancy
ACTION OF THE HORMONES ON UTERUS
Amniotic liquid
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Metoestrus with pregnancy
ACTION OF THE HORMONES ON UTERUS
Ultrasonography
Uterine lumen
Fœtal ampulla
. Closed cervix
progesterone
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Metoestrus without pregnancy
ACTION OF THE HORMONES ON UTERUS
. Uterine milk
. Very developed uterine mucosa
Propitious conditions for bacterialmultiplication
Opened cervix
Suppression of
progesterone
Involution of uterus
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End of Metoestrus or parturition
ACTION OF THE HORMONES ON UTERUS
Restart of uterine
contractions
Inactive uterus,
thin uterine mucosa without
foldsThe cervix is
not always completly hermetic
Mucous plug
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Anoestrus : sexual inactivity
ACTION OF THE HORMONES ON UTERUS
MEDICAL METHODS TO TERMINATE CANINE PREGNANCY
/ Estrogens/ Prostaglandins/ Inhibitors of progesterone synthesis (Epostane)/ Ergoline derivatives (Bromocriptine, Cabergoline)/ LHRH antogonists (Detirelix and RS15378)/ Antimitotic agents/ Tamoxifen/ Corticosteroids treatments
MEDICAL METHODS TO TERMINATE CANINE PREGNANCY
/ ESTROGENSmainly estradiol benzoatemode of action (hypothesis):
modification of the mobility of uterotubal junction and expulsion of premature ova or delayed transport of the ova in the oviduct (=>degeneration)modification of the biochemical environment of oviduct and uterus (induction of histological change of implantation site)
side effects:extended estrushigh risk of cyctic endometrial hyperplasia and pyometra
MEDICAL METHODS TO TERMINATE CANINE PREGNANCY
/ PROSTAGLANDINSadministration during 2nd half of the luteal phasemode of action:
gradual and complete luteolysis (=> lowering of plasma progesterone concentration)possible uterine contractions (PGF2 alpha) and dilatation of cervix
disadvantages and side effects:Off label useineffective on early pregnancy (days 5 to 17)salivation, vomiting, diarrhoea, hyperpnea and ataxia (limited by use of atropine => antagonises also uterine contractility)
MEDICAL METHODS TO TERMINATE CANINE PREGNANCY
/ INHIBITORS OF PROGESTERONE SYNTHESIS (EPOSTANE):
mode of action:decrease of progesterone synthesis from pregnenolone through inhibition of an enzyme of steroidogenesis (3-beta-hydroxy-steroid-dehydrogenase) termination of pregnancy if administration during metoestrus
disadvantages and side effects:Off label usedevelopment of large abscesses if administration by subcutaneousroute
/ ERGOLINE DERIVATIVES (BROMOCRIPTINE, CABERGOLINE):
mode of action:inhibition of prolactin secretion (direct stimulation of dopamine receptors on pituitary cells)lost of luteotrophic support of the corpus luteum and decrease of plasma progesterone concentration (administration from the second half of luteal phase = day 42) => abortion
disadvantages and side effects:Off label uselong administration: 4 days (bromocriptine) to 5 days (cabergoline)action on CNS: vomiting, nausea, anorexia and polydipsia (less severe action for cabergoline)
MEDICAL METHODS TO TERMINATE CANINE PREGNANCY
MEDICAL METHODS TO TERMINATE CANINE PREGNANCY
/ LHRH ANTAGONISTS (DETIRELIX, RS15378):mode of action:
action in very early stages of developmentstimulation of synthesis and release of gonadotrophic hormones => modification of synthesis of steroids hormones in gonadssuppression of luteal function from day 20 of pregnancy => resorptionand abortion
disadvantages and side effects:Off label usehigh doses are requiredmast cells degranulation (release of histamine and inflammatory mediators)less severe with RS15378
MEDICAL METHODS TO TERMINATE CANINE PREGNANCY
/ ANTIMITOTIC AGENTS:phenyl-triazole iso-indole (Privaprol), isoquinoleinesmode of action:
degeneration of the conceptus (absorbed and expelled)acts after implantation of the ova in the uterus
side effects:pyometra in treated dogs
/ TAMOXIFEN (Off label use):pure antiestrogen (with no agonistic effect): higher affinity for estrogen receptors than estradiol
MEDICAL METHODS TO TERMINATE CANINE PREGNANCY
/ CORTICOSTEROIDS TREATMENTS:mode of action:
the exact mode of action is not known
disadvantages and side effects:Off label useadministration in 2nd half of pregnancylong treatmentcorticoids side effects: polyphagia, polydipsia and polyuria
MEDICAL METHODS TO TERMINATE CANINE PREGNANCY
PRODUCTS PERIOD OF EFFICACY DISADVANTAGES
Estrogens Efficient before implantation of the ova intouetrus
Estrus extension Bone marrow hypoplasia Cystic endometrial hyperplasia Pyometra Repeated administration
Prostaglandins Efficient on the 2nd half of the luteal phase Salivation, vomiting, diarrhoea,respiratory distress
Repeated administrationsErgoline derivatives Efficient on the 2nd half of the luteal phase Inefficient on the 1st half ofpregnancy
Action on CNS : nausea, apathy,anorexia, polydipsia
Repeated oral administrationInhibitors of progesterone synthesis Efficient before ova implantation in uterus Large abcesses (SC route)
Repeated injections
LHRH antagonists Efficient from day 20 of pregnancy High dosages required Mast cells degranulation (histamine,
inflammatory mediators)Antimitotic agents No hormonal activity
10 – 12 days after mating Severe side effects (pyometra)
Tamoxifen Efficient early in the pregnancy Repeated administrations by oral route
Corticosteroids Long treatment Polyphagia, polydipsia and polyuria
Excepted estrogens and some antimitotic agents like Privaprol: OFF LABEL USE