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Fertility Problems and Litter Loss

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The process of reproduction relies on many complex factors such as: healthy male sperm, a viable egg, a healthy reproductive system in the female, embryos of equal quality, environmental stability, nutrition, and avoidance of pathogens that affect reproduction.

Impairment to any one of these factors may result in infertility. Healthy rats bred during the proper breeding ages that are provided with essential nutrition, a low stress environment, and are free from genetic disorders and certain infectious agents will generally have successful pregnancies.

Known variables of complication in breeding include genetic problems, viral and bacterial pathogens, nutritional deficiencies, and environmental dynamics.

Male Infertility
In male rats low sperm count may occur with a pre-existing genetic condition, a hormone disorder, or blockage from previous infection. Heart disease can cut down on the oxygen levels in an affected rat’s system and affect sperm production. Infertility may also result from cryptorchidism or other testicular abnormalities. Age in the male rat may also be evidenced by decreased fertility although the sperm generally are still viable.

Female Infertility
In female rats infertility often occurs when there are problems with ovulation. Common causes of infertility include: tubal blockage, hormone imbalance, tumors and cysts in the reproductive system, thyroid conditions, and disease.

Of the maternal diseases, diabetes generally results in fetal hyperglycemia and hyperinsulinemia causing growth retardation. Rats with diabetes during pregnancy have been shown to produce offspring that develop diabetes as adults.

Other factors that impact fertility and litter loss in female rats pertain to age, weight, and stress factors. Older females can either cease formation of eggs or have eggs that are less viable. Obesity puts a strain on the body, can result in infertility, larger pup birth weight, cause fetal and neonatal death, contribute to birth defects, and complicate the birth process. On the flip side, underweight females can have litter reabsorption or low birth weight babies.

Infectious Agents

Sendai virus- causes immunosuppression and decreased fertility as well as neonatal and adult deaths. It has also been reported to be the cause of slow growth in young rats.

Parvovirus- has been shown to cause decreased fertility, fetal reabsorption, small litters, and runting of pups. The strain usually seen with this type of effect is Kilham�s rat virus (RV or KRV) Generally an infection with RV will stay active for about 3 months, after which females in the colony usually return to normal pregnancies/births although the infection is still present.

Rat Corona virus- is reported to cause decreased fertility. This can include SDAV (sialodacryoadenitis virus) as well as other strains.

Mycoplasma pulmonis- in pregnant rats can cause a lower litter weight and a high resorption rate, in addition to stillbirths and macerated fetuses.

Pathology can include uterine horns and endometritus. It has been shown to adhere to spermatozoa in an in vitro system.

Murine Genital Mycoplasmosis- in the female causes infection of the oviduct and uterus. Infertility, embryonic resorption and small litters may occur. Research has shown that this pathogen can induce inflammation in the epididymis of males.

Pasteurella pneumotropica- is often associated with Mycoplasma pulmonis and/or Sendai and has been found to localize in the intestinal tract in subclinical infections.

The occurrence of lesions may be found in the mammary glands, uterus, lymph nodes, accessory sex glands and the urinary system, causing infertility, abscesses, pyometria and abortion.

Salmonellosis species that generally effect rats include enteritides and S. typhimurum. Signs of this infection include small litters and abortion.

Nutritional Factors

Breeding animals have special nutritional requirements. If not maintained the resulting deficiencies will cause a detrimental effect on reproduction. Pregnant and nursing rats require more protein and fat to compensate for milk production and fetal development. Inadequate maternal diet can limit the energy supply of the embryo and hinder essential changes in DNA.

Typically a rodent block formulated specifically for laboratory breeding colonies takes away any guesswork. This can then be supplemented with healthy fruits, vegetables, grains, and low fat protein.

Studies have shown that protein deficiency can cause problems in the liver and pancreas, disturbing the metabolism of the fetus.

Severe lack of nutrition during pregnancy can lead to IUGR (intrauterine growth retardation), with placental weights significantly reduced, as well as postnatal growth failure and absorption of the litter in utero.

Since rats have the capacity to ovulate within 24 hours of parturition (delivery) they may become pregnant again just before lactation begins, and therefore pregnant and lactating simultaneously.

In the event of food deprivation the litter in utero will be absorbed if the pregnancy is less than halfway. If the fetuses are further developed the mother may diminish milk production. This may lead to the loss of some of the litter so that it may be consumed for protein.

Either way “back-to-back” pregnancies are not conducive to fertility and health in either the offspring or the mother.

Overfeeding
Of interest to the contrary side of this equation, over fed rats may have difficult pregnancies and see a decrease in birth rate through several generations. In a study, conducted by the University of Washington in 1997, newborn rats were over fed to replicate nutritional conditions during late human pregnancy that often affect babies of diabetic mothers. Many of the over fed first generation showed significant weight gain, had difficulty with pregnancy, and showed a birth rate that was 70% of normal rats. In the second generation the weight factor reversed and the rats were significantly smaller than normal. Reproduction problems continued and birth rate was 57% of normal rats. Third generation over fed rats weighed the same at birth as normal rats but experienced a growth spurt nine days after birth. By three weeks of age they were 15% bigger.

Vitamins and Minerals in Pregnancy

Deficiency of vital nutrients can affect fertility and the health of offspring. It is essential to provide your breeding and lactating rats with a well rounded diet that fills their nutritional needs.

Vitamin A
Insufficient vitamin A throughout rat pregnancy is well documented, altering the placenta and subsequently causing defects in embryos in addition to infertility. Vitamin A is also crucial during embryological growth when cells are proliferating, and can lead to defects in the hindbrain, heart and skeleton. Deficiencies later in rat life can lead to anomalies in the eye, kidney, heart, lungs and urogenital system. Severe insufficiency of this vitamin can induce abortion and fetal deaths, which occurs when reserves of this maternal tissue is so drained that decrease in noticeable in the ocular system, one of the last areas to lose its supply. Vitamin A is also essential during lactation to replace the breast milk.

Vitamin B/ Folic Acid
B vitamin deficiency two weeks before mating reduces female fertility by up to 80%. Vitamin B and folic acid are helpful in the development of the neural tube and help offset certain birth defects such as anencephaly.

Copper
Copper is essential for brain development. Lack of copper during pregnancy reduces brain levels and complicates development of the nervous system. Associated with motor function, poor coordination can be a symptom of copper deficiency.

Environmental Dynamics

Environmental factors that can have negative impact upon pregnancy include stress, lighting and temperature, cigarette smoke, drugs, pesticides and solvents.

Stress
Rats’ response to stress is hormone-regulated. Severe stress can trigger abnormal physiological changes such as glandular malfunction, diminished ovulation and implantation, inadequate lactation, susceptibility to disease and increased infant mortality, and even spontaneous abortion. In extreme cases females have been known to devour their young when stressed.

Excessive handling and noise may induce stress. The acute hearing of rats renders them sensitive to high-pitched sounds. Many research facilities have altered alarm systems to avoid disturbing mothers with newborns.

Light
Cycles of light and darkness are also important in breeding rats, and they should be provided with 12 hours of light and 12 hours of darkness. Deviating from this cycle can affect the reproductive process. Duration and type of lighting can also affect estrus behavior. Rats exposed to noise and flashing lights during pregnancy had an increased absorption rate and variation in fetal weights.

Subtle variations in temperature and humidity have been shown to cause decreased reproductive efficiency. Proper ventilation can have an impact, reducing the spread of disease. It also provides a stable temperature and lessens the chance of drafts.

Smoke
In utero exposure to second-hand smoke in rats leads to an increased sensitivity of the aortic rings, suggesting a compromise of vascular smooth muscle function. Research has shown a significant reduction of body mass and birth weight of newborns after in utero exposure to tobacco smoke. The cyanide in tobacco smoke can also cause reduction in vitamins B12 and C.

Retardation of bone formation has occurred in newborn rats whose mothers were exposed to smoke during pregnancy. Histological changes have been observed in the lung, liver, kidney, stomach and intestine of young rats, including hyperplasia of bronchial muscles, which is a pre-cancerous stage.

Drugs
Drugs that can affect male rat impotence include diazepam, chlorpromazine and estrogens. Tetracycline administered to pregnant females can impede the development of bones and teeth of the fetus. Aspirin has caused birth defects in rats.

Poisonous Substances
Ingestion of lead can impair testicular endocrine function. Agents that may also affect germ cell chromosomes and DNA include mercury and cadmium.

Male rat reproductive disorders can be triggered by exposure to chemicals that change hormone levels while still in the womb. Industrial solvents widely found in the environment inhibit a male sex hormone causing malformation of the epidydmis, penis and testicles.

Chemical plasticides, pesticide surfactants and PCB have all been linked to reproductive tract malformations and sterility in male animals.

Conclusion

Although there are quite a variety of elements that can affect fertility and litter loss in rats, it is common sense and education that can prevent these problems. A good way to judge whether or not you are providing a healthy breeding environment is to look at the elements and ask, “Would this be suitable for me or my children?” Suddenly any stressors in the environment, any lack of nutrition needs, or exposure to harmful agents takes on a different perspective. For the most part their requirements are very similar to ours.

Resources
  • Animal Use on the UIUC Campus Policies Pertaining to the Care and Use of Animals in Research and Teaching: Major Rodent Pathogens. (n.d.). Retrieved December 19, 2008, from http://research.illinois.edu/IACUC/files/PolicyPDFs/rodent_pathogens.pdf.
  • Antipatis, C., Ashworth, C., Riley, S., Hannah, L., Hoggard, N., & Lea, R. (2002). Vitamin A deficiency during rat pregnancy alters placental TNF-alpha signalling and apoptosis. Am J Reprod Immunol, 47(3), 151-8. Retrieved December 19, 2008, from the Medline database.
  • Brown, M., & Shofield, J. (1990). Essential for animal research: A primer for research personnel: Chapter 3: Animal care and use: A experimental variable. Beltsville: National Agricultural Library.
  • Haugaard, C., & Bauer, M. (2001). Rodent models of intrauterine growth restriction. (2001). Scand. J. Lab. Anim. Sci. Vol. 28(1), 10-22. Retrieved December 19, 2008, from http://biomedicum.ut.ee/sjlas/28_1_10.pdf.
  • Hutchison, S., Glantz, S., Zhu, B., Sun, Y., Chou, T., Chatterjee, K., Deedwania, P., Parmley, W., & Sudhir, K. (1998). In-utero and neonatal exposure to secondhand smoke causes vascular dysfunction in newborn rats. Journal of the American College of Cardiology, 32(5), 1463-1467. Retrieved December 19, 2008, from the Medline database.
  • Infectious Agent Exclusion List for Rats. (n.d.). Retrieved December 19, 2008, from http://www.research.usf.edu/cm/CMDC/C117_1_Infectious_Agent_Exclusion_List_Rats_8_06.pdf.
  • National Research Council., Institute of Laboratory Animal Resources., Commission On Life Sciences., & Committee On Infectious Diseases of Mice and Rats. (1991). Infectious Diseases of Mice and Rats. Washington, D.C.: National Academies Press.
  • Rat Diseases. (n.d.). Retrieved December 18, 2008, from http://www.IDEXX RADIL.missouri.edu/info/dora/RATPAGE/rat.htm.
  • Reece, E., Homko, C., & Wu, Y. (1996). Diabetic embryopathy. Fetal and Maternal Medicine Review, 8(4), 187-197. Retrieved December 19, 2008, from http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=47197.
  • Schwarz, J. (1997, October 28). Overfeeding normal infant rats affects three generations. Retrieved December 19, 2008, from http://uwnews.washington.edu/ni/article.asp?articleID=2968.
  • Steiner, D., & Brown, M. (1993). Impact of experimental genital mycoplasmosis on pregnancy outcome in Sprague-Dawley rats. Infect Immun, 61(2), 633-9. Retrieved December 19, 2008, from the Medline database.
  • Woerpel, R., & Rosskopf, W. (n.d.). Mice/Rats Reproduction. Retrieved December 19, 2008, from http://www.animalhospitals-usa.com/small_pets/mice_rats_reproduction.html.

Posted on November 25, 2005, 12:18, Last updated on January 1, 2009, 20:41 | Pregnancy



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