Feline reproduction: An overview (Proceedings)
Margaret V. Root Kustritz, DVM, PhD, DACT
Department of Veterinary Clinical Sciences
In veterinary medicine, cats are too often treated as strange small breed dogs. To those who work with cats every day, the fallacy of this supposition is obvious.
In veterinary medicine, cats are too often treated as strange small breed dogs. To those who work with cats every day, the fallacy of this supposition is obvious. To those who deal with cats only occasionally, this inaccuracy must be recognized since cats now outnumber dogs as the preferred household pet in the United States and cat owners expect veterinarians to be familiar with the husbandry, normal physiology and diseases of this species.
Cats appear to reproduce well without veterinary intervention, leading some to question the necessity for the study of feline theriogenology. Bastet, the Egyptian goddess of fertility, was represented as a cat. It is true that fewer cats than dogs are presented as clinical cases to small animal reproductive specialists; at the University of Minnesota, only 7/158 (4.4%) of animals presented to this clinician over a 3 year span were cats, with 71.0% of those presenting with ovarian remnant syndrome. However, increased understanding of feline reproduction will serve veterinary medicine beyond clinical practice. Studies of normal feline reproductive physiology and reproductive technology, such as artificial insemination and in vitro fertilization, can be extrapolated for use in the 36 species of wild felids, all of which are threatened or endangered. Information about regulation of estrus activity and spermatogenesis can be used in development of effective contraceptives and knowledge of pregnancy used for development of safe and efficacious pregnancy termination protocols, all of which will benefit those working to control feral cat populations and the current overabundant domesticated cat population.
Female cats go through puberty, defined by onset of their first estrus, at an average age of 8-9 months, with a range from 4-18 months. Long-haired breeds enter puberty earlier in life than short-haired breeds. Puberty onset is also dependent on season; cats reaching an appropriate age during the seasonal anestrus will not go through their first estrus until the breeding season begins.
Cats are seasonally polyestrous, cycling for an average of about 6 days every 2-3 weeks from January through mid-October. The seasonal anestrus from mid-October through December is defined by day length; cats maintained under artificial lights for 12 continuous hours daily will cycle year-round and may exhibit increased fertility. Length of estrus may or may not be affected by breeding. Some studies suggested a shortening of estrus in bred cats while others showed no effect of breeding. Bred cats that are induced to ovulate but do not conceive will undergo a prolonged luteal phase, lasting 45-60 days. Induction of ovulation in estrous queens may be used to decrease cyclic activity between desired breedings.
Proestrus is not routinely discernible in cats. Shille et al documented proestrus in only 27/168 (16.1%) of cycles followed. Estrus behaviors in the cat include monotonous vocalization, increased affection, lordosis (elevation of the hindquarters with lateral deviation of the tail) and rolling. A positive correlation has been shown between estrous behavior and cornified vaginal cytology. Cornified vaginal cytology specimens may be useful in defining estrus in queens which exhibit no overt estrous behavior. Cats may rarely have clear vulvar discharge associated with estrus.
Cats are induced (reflex) ovulators, as are rabbits, ferrets, mink, skunks, 13-lined ground squirrels, camels, llamas, short-tailed shrews and giant fruit bats. In these species an external trigger, usually coitus, stimulates release of gonadotropin releasing hormone (GnRH) from the hypothalamus. This stimulates release of luteinizing hormone (LH) from the pituitary within 2-4 hours, which will then cause ovulation in 1-3 days. The amount of LH released in dependent on the number of copulations and the time during the estrous cycle when copulation occurs. Queens bred only once exhibit great variability in serum LH concentrations and fewer than 50% will ovulate. Concannon et al demonstrated that greater than 4 copulations were required to insure LH release adequate for ovulation.
In the colony at the University of Minnesota, 14 cats were bred at 23 cycles. They were bred an average of 5.6 times per cycle, with a range of 4-8 times per cycle. The pregnancy rate was 73.9%, and those queens that did not become pregnant had prolonged interestrous intervals, averaging 61.5 ± 14.5 days in length. This suggests that breeding an average of 5.6 times/cycle was sufficient for reliable induction of ovulation.
There is some evidence that cats may occasionally spontaneously ovulate. Wildt et al failed to demonstrate spontaneous ovulation in 17 queens by laparoscopy. However, cats housed at Ralston Purina were noted to have high incidence of uterine disease, an unexpected finding in cats which were not induced to ovulate. Serial blood samples were drawn from 20 queens that were housed individually and who had no perineal contact with other cats or from their handlers. Thirty-five percent of these cats had serum progesterone concentrations suggestive of ovulation at one or more samplings. This suggests that queens may occasionally spontaneously ovulate, may ovulate secondary to a trigger other than coitus, or may undergo luteinization of follicles instead of atresia after a non-ovulatory cycle.
Tom cats go through puberty, defined by first appearance of sperm in the ejaculate, at 8-12 months of age. The penis of male cats is encircled at the level of the corpus cavernosum glandis by 100-200 cornified papillae, commonly called penile spines. These are androgen-dependent; they appear at 6-7 months of age and disappear after castration. Mature tom cats are capable of mating repeatedly over a 4-5 day period without a decrease in sperm numbers. Males maintained under 12 hours continuous light daily showed no seasonal change in breeding behavior or semen quality.
Breeding behavior in the cat is unpredictable and quick. Copulation consists of mounting of the queen by the tom, positioning of the tom and erection of the penis, intromission and ejaculation by the tom, dismount of the tom and the "after-reaction" by the queen. The "after-reaction", as exhibited by queens in the colony at the University of Minnesota, consists of striking out at the male (76.9% of 120 breedings witnessed), vulvar licking (92.3%) and frantic rolling (100.0%). Some queens exhibited hypersalivation and frantic licking at the rear limbs and back. The entire copulatory sequence is reported to take from 0.5-9 minutes.
Historically, it was thought that the engorged penis of the tom and/or the penile spines stimulated the cervix of the queen to induce ovulation. Watson and Glover recently demonstrated that queens will not emit a characteristic coital vocalization when the cervix is probed, but will when the posterior vagina is stimulated. They also showed that the erect penis of the tom cat is too short and too large in diameter to reach the cervix of the queen, suggesting that stimulation of the posterior vagina is necessary for ovulation induction in this species.
Artificial insemination requires induction of ovulation by administration of gonadotropin releasing hormone (GnRH; 25 mcg IM) or human chorionic gonadotropin (hCG; 100-250 IU) on day 2-4 after estrus onset followed 24-48 hours later with insemination of semen collected by manual ejaculation or electroejaculation. It is reported that at least 80 million spermatozoa must be introduced; reported conception rate varied from 57-78%. There is evidence that treatment with chorionic gonadotropin to induce ovulation may promote development of ancillary follicles with subsequent excessive estrogen production that impairs oviductal transport of fertilized embryos. Advanced reproductive technologies, including embryo transfer and cloning, have been successfully performed in cats but are not readily available.
Pregnancy diagnosis in the cat is easily accomplished by abdominal palpation after 21 days post-breeding, by ultrasonography after 21-30 days post-breeding and by radiography after 37 days post-breeding. If a single radiograph is not definitive for pregnancy, a second radiograph taken 5 days later should show progressive mineralization from proximal to distal. Fetal viability is best assessed by ultrasonography. Fetal number and gestational age are best assessed by radiography; crown-rump length has been correlated with gestational age in this species. One study suggested that a serum progesterone concentration of > 5 ng/ml at 6 or more days post-breeding is indicative of pregnancy with 81% accuracy in the cat. The canine relaxin assay for pregnancy diagnosis (Witness, Synbiotics, San Diego CA) has been demonstrated to be accurate for pregnancy diagnosis in cats from days 20-29 of pregnancy.
Gestation length in the colony at the University of Minnesota averaged 66.9 ± 2.9 days, with a range of 62-71 days. This is not significantly different from average gestation length previously reported, at 63.8-66.0 days, with a range from 52-71 days. The variability in gestation length may be partially explained by the variability in time of LH release and subsequent ovulation after multiple breedings.
The source of gestational progesterone is debated in the cat. Traditionally, the work of Scott, demonstrated maintenance of normal pregnancy despite ovariectomy at 45-50 days of gestation and Malassine and Ferre, who demonstrated ability of the feline placenta to synthesize progesterone from pregnenolone, supported a placental source of progesterone in late gestation. Recently, Verstegen et al demonstrated a decrease in serum progesterone concentrations and subsequent abortion in cats ovariectomized at day 45 of gestation or treated with an inhibitor of prolactin secretion, cabergoline, from days 30-35 of gestation, suggesting that maintenance of the corpus luteum is crucial for maintenance of normal pregnancy.
Queening and rearing of kittens
Dystocia is not uncommon in the cat, with one retrospective study reporting an incidence of 3.0%. Dystocia in cats is more commonly due to maternal causes than fetal causes, with uterine inertia the primary reported cause. There is no reported correlation between occurrence of dystocia and age of the queen or litter size. Medical therapy with oxytocin with or without calcium, and surgical therapy (cesarean section) have been described. En bloc ovariohysterectomy has been reported as a surgical means of dystocia resolution in cats.
Parturition usually occurs at night. Decline in body temperature prior to parturition is not a consistent finding in cats. The stages of parturition are the same as in the dog; Stage I = cervical dilation, Stage II = passage of neonates and Stage III = passage of placentas. Posterior and anterior presentation are equally common during normal parturition. Average parturition length has been reported to be 16.1 ± 14.3 hours, with a range of 4-42 hours; median parturition length was 8 hours.
Litter size in the colony at the University of Minnesota ranged from 1-5, with an average of 3.7 kittens per litter. This agrees with values for average litter size in the literature, which range from 2.8-4.2 kittens per litter.
Overall juvenile mortality by 8 weeks of age has been reported at 27.3% and 29.1%. Causes of juvenile mortality at the University of Minnesota included stillbirths, cannibalism, intussuseption and enteritis. Congenital defects noted in this colony included diabetes mellitus due to endocrine pancreatic insufficiency, cryptorchidism and anogenital malformation.
Ovarian remnant syndrome
Ovarian remnant syndrome (ORS), which has been defined as presence of functional ovarian tissue in a previously ovariohysterectomized queen, is a common reproductive problem in female domestic cats. Cats with ORS most often are presented by the owner for the primary complaint of exhibition of estrous behavior following ovariohysterectomy (OHE). The interval between OHE and first appearance of estrous behavior is variable, with a reported range of 2 weeks to 9 years. The month of onset may depend on season of the year; many cats first show signs of ORS starting with increasing day length in late December to early January, when most cats at this latitude resume cycling after the normal winter anestrus.
One cause of ORS is surgeon error, if a piece of ovary is left behind during OHE. Residual ovarian tissue may revascularize and become functional. It is possible that individual cats may possess accessory lobes of the ovaries, but these are considered to be very rare in domestic animals. Estrous behavior also can be initiated in cats with the administration of estrogens; a thorough drug history should be taken. No correlation has been demonstrated between incidence of ORS and age at the time of OHE or breed of the cat, nor is the syndrome more common in cats spayed by new graduates. All reported ovarian remnants have been found at the ovarian pedicle; in one study, 27% were bilateral. Granulosa cell tumor has been reported on histopathologic evaluation of ovarian remnant syndrome in one cat.
Vaginal cytology is easily performed in the cat, and is an inexpensive, accurate way to detect estrogen presence in the body. Increased concentrations of circulating estrogen, produced by the developing follicle, stimulate proliferation of stratified squamous epithelium in the vagina. Vaginal cytology should be performed when the cat is in behavioral estrus. Vaginal epithelial cells can be collected with a saline-moistened cotton tipped swab, as in the dog. The swab is gently rolled onto a glass slide and stained with new methylene blue or Wright's stain. A smear representative of estrus consists of numerous cells, often clumped, and the majority of which are large with irregular, folded cellular borders. The nuclei may be pyknotic or fail to take up stain.
Hormone assays can be performed to aid in diagnosing ORS. The measurement of resting concentrations of estradiol or progesterone is generally unrewarding. However, by using hormone challenge testing, elevated concentrations of progesterone may be induced. The administration of GnRH (25 mcg/cat IM) to an estrous queen with ORS often results in elevated serum progesterone concentrations. The serum sample should be drawn 2-3 weeks following administration of GnRH; serum progesterone concentrations of greater than 2 ng/ml indicate presence of functional luteal tissue.
ORS can be treated medically or surgically. Medical treatment consists of estrus suppression for the life of the animal. Since there are currently no drugs approved for estrus suppression in the cat, and surgical treatment usually is curative, surgical therapy is the treatment of choice.
Exploratory laparotomy can be performed when the cat is in behavioral estrus, in which case the surgeon is looking for follicular tissue, or 2-3 weeks after administration of GnRH, in which case the surgeon in looking for luteal tissue. The advantage of the latter is that there may be less bleeding during diestrus, due to lower serum estrogen concentrations, and corpora lutea persist longer than follicles. Surgery should be performed within 30 days of administration of GnRH. The residual tissue virtually always is present at one or both of the ovarian pedicles. If no obvious ovarian tissue is present, granulation tissue at the site should be removed, being careful not to ligate the ureter.
Neonatal isoerythrolysis is an acute disease of kittens in the first days of life. Cats have naturally occurring antibodies blood types they are lacking; development does not require previous pregnancy or transfusion. There are two main feline blood types, A and B. Some type A cats (16.4%) have weak anti-B antibodies while all type B cats (100%) have strong anti-A antibodies. Kittens with blood type A born to type B queens become acutely ill after ingestion of colostrum and absorption of her anti-A antibodies.
Clinical signs in the kittens include anemia, icterus, tail tip necrosis due to hemagglutination in peripheral capillaries and localized thrombus formation, weakness, tachypnea, tachycardia, hemoglobinuria, and sudden death. Severity of signs may vary within the litter, presumably due to variability in antibody uptake.
The mortality rate is high in affected kittens, even with prompt intervention. The kittens should be removed from the dam and transfused if necessary. The dam is a good blood donor since she has no antibodies to her own red blood cells.
Prevention involves avoiding incompatible matings (type B queens to type A toms). Estimation of proportion of incompatible matings by breed is 0.25% for domestic short-haired cats, and as high as 14-25% for Persians and Abyssinians. The type B blood type is most prevalent in the Devon and Cornish Rex and British Shorthair breeds (see table below). Blood-typing can be performed in-house (DMS Laboratories, Flemington NJ, 1-800-567-4367) or by commercial laboratories. Blood typing can be performed on umbilical cord blood from kittens to forestall problems in litters from untested queens and toms.
Frequency of type A and B blood in cats in the United States