Tag: pregnancy

Science

Gene therapy may hold promise for cat birth control

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Meredith Hemphill

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Tabby cat carry her kitten
Image by Rajesh Balouria from Pixabay

Last month, an article was published in Nature Communications by a team of scientists from the Cincinnati Zoo and Botanical Garden, the Horae Gene Therapy Center, and Massachusetts General Hospital [7-9]. They tested a gene therapy injection as an alternative to spaying and neutering for cat birth control, and the results are exciting.

Why do we need cat birth control?

80% of the estimated 600 million domestic cats in the world are strays or feral [4, 9]. Cat overpopulation leads to more disease and greater loss of birds and other small animals from predation [2-6]. Animal shelters become overrun with homeless kittens and cats, and many are ultimately killed. Cats reproduce very quickly, so it doesn’t take long for a few to become a serious overpopulation issue. The only method of sterilization currently available is spay/neuter surgery. It is effective and permanent, but there are drawbacks.

Surgical sterilization has to be performed by a veterinarian at a surgical clinic [2]. It’s an invasive procedure for females, and both sexes are supposed to have a recovery period, including medication [2]. It’s also expensive [2, 6]. Those resources are in short supply, even more so in developing countries [1, 2, 6]. Thus, there has been interest in non-surgical cat contraception for years. Previous attempts have included vaccines targeting the pituitary gland, toxins targeting reproductive cells, and RNA-silencing drugs to shut down the genetic mechanism of conception [1, 3, 5]. All were either ineffective or unsafe [3, 5].

The Alliance for Contraception in Cats and Dogs (ACC&D) was founded in 2000 with the goal of finding a one-time, permanent, non-surgical contraceptive that would help to curb the overpopulation of homeless cats and dogs [1, 5]. ACC&D wasn’t involved in this study, but ACC&D President Joyce Briggs said, “This research is a huge leap—we’re really excited about it” [1, 5]. She also noted that the lead author, Dr. Lindsey Vansandt, is someone they have worked with before on a contraceptive vaccine called GonaCon [1].

The organization that provided the primary funding for the Vansandt research team has a similar goal. The Michelson Found Animals Foundation was founded in 2009 by inventor Gary Michelson [1, 2, 5]. Its goal is also a single-use, permanent, non-surgical dog and cat birth control, although specifically as a marketable product [1, 2]. Toward this end, the Michelson Found Animals Foundation created the Michelson Prize, $50 million (USD) in research funding plus $25 million if successful [1, 2, 5, 7]. So far, they have given out 41 grants [1, 5].

David Grimm, a journalist for Science, explained that it can be very difficult to get funding for this kind of research; most of the money goes toward studying the human body. So the Michelson Prize grants have been a huge boost to searching for a better companion animal contraceptive. [2]

The Experiment

Dr. David Pepin didn’t have his eyes on the Michelson Prize at first, however. Pepin was looking for ways to help women with ovarian cancer preserve their fertility [6-8]. He was studying anti-Müllerian hormone (AMH), sometimes called Müllerian inhibiting hormone (MIS), which made by the ovarian follicles of female mammals [1, 2, 4-8]. An ovarian follicle is a layer of cells around an egg that nourish the egg as it grows and matures.

Pepin was trying to learn more about what AMH does, so he injected an extra copy of the AMH gene into female mice [2, 4, 5]. This technique, sometimes called gene therapy, does not change the native DNA. It adds new, free-floating pieces of DNA into the cells, complete with all the information the cells need to read the “instructions” on the new piece of DNA. Gene therapy has been used to treat genetic diseases in humans, hence the name, but in this case Pepin was using the same procedure for research purposes to see how the mice would respond to high levels of AMH. He was surprised when the mice’s ovaries shrank, stopped producing eggs, and became infertile [1, 2, 4-6].

“We thought, well, this is a very interesting tool, but what can we use it for?” Pepin said [4]. He decided to submit an application for a Michelson Prize grant, and Bill Swanson, Director of Animal Research at the Cincinnati Zoo, happened to review it [1, 2, 4, 5]. Swanson had actually been working on an opposite project, trying to increase breeding in captive big cats [2, 5]. However, the Cincinnati Zoo maintains a research colony of domestic cats, and Swanson thought Pepin’s proposal was a great idea, so a partnership was struck [2, 4, 5].

Diagram of cat birth control experiment
Experimental design – From Vansandt et al. 2023

The study was small, with three groups of only three she-cats each [3-5, 7, 9]. The nine cats were all named after former first ladies: Michelle, Betty, Abigail, Nancy, Dolly, Barbara, Rosalyn, Jacque and Mary [4]. The domestic cat gene for AMH was constructed into a piece of DNA that the cats’ cells could read, and then that piece of DNA, named fcMISv2, was taken up by the harmless AAV9 virus [9]. Viruses are used in gene therapy because they naturally have the ability to insert genetic material into cells. Three cats served as a control group and were injected in the thigh muscle with AAV9 viruses that were empty, no DNA to inject [3, 7, 9]. Three cats were injected with a lower dose of viruses carrying the gene, and the other three received a higher dose [3, 7-9].

The experimental cats’ muscle cells successfully incorporated the fcMISv2 DNA and began to make AMH [9]. According to Pepin, “A single injection of the gene therapy vector causes the cat’s muscles to produce AMH, which is normally only produced in the ovaries, and raises the overall level of AMH about 100 times higher than normal” [7, 8]. Although their AMH levels increased, only progesterone decreased in response [5, 9]. Their other hormone levels remained the same, their hormone cycles were unaffected, and they showed no signs of adverse side effects [2, 3, 5, 7-9].

During two mating trials, two different toms were each introduced to the nine she-cats for four months at a time [3, 5, 7, 9]. All of the cats in the control group mated, became pregnant, and gave birth to kittens [3, 5, 7-9]. Only two of the cats who received gene therapy even allowed the toms to mate, and none of them ever became pregnant or had kittens [3, 5-9]. At the end of the two-year study, they were maintaining steady, elevated AMH levels, and the scientists are cautiously optimistic that this method may be a permanent contraceptive [5, 7-9].

What happens next?

It remains unclear exactly how AMH functions as kitty birth control [1, 2, 5, 9]. The researchers believe that the elevated levels of AMH prevent she-cats’ follicles from developing and thereby prevent ovulation [2-5, 9]. However, more research is needed to understand exactly how AMH works, and to answer lingering questions.

For instance, is this sterilization truly permanent [1, 2, 6]? The scientists who authored the study believe it is, but they only tested those cats for two years, so no one can say for sure yet that it doesn’t eventually wear off. Are there any negative side effects that they didn’t catch in such a small study [6]? Could AMH work for dogs, too [1, 2, 5, 6]? That is an important goal of this kind of research, not to mention a requirement to win the Michelson Prize [1, 5]. There are also concerns about cost, as that is often what prevents people from spaying and neutering cats now [1, 2]. If a new AMH shot will cost as much or more than surgically sterilizing cats, the convenience of the one-dose injection won’t really matter [1, 2].

Pepin, Swanson, and the Michelson Foundation are already in talks with the Food and Drug Administration about a larger trial and the possibility of bringing an AMH drug to market [2, 5, 6], so keep your ear to the ground. In the meantime, GonaCon, the cat birth control vaccine that study author Lindsey Vansandt worked on with ACC&D, has shown promise as well and may actually be closer to becoming available [1]. Either way, this area of study appears to be accelerating, and there may be more exciting news to come in the next few years.

Two kittens peeking through hole in wooden wall
Effective feline contraception means fewer homeless kittens – Image by Sommer from Pixabay

As for the cats from the study, they were all put up for adoption after the research concluded [4]. This is something the Cincinnati Zoo does with their research participants–Bill Swanson already has three cats he adopted from previous studies [4]. I couldn’t find out if all nine have been adopted yet, so if you live in the Cincinnati area and are looking for a new feline friend, email [email protected]. The cats’ new owners are asked to bring them back to the zoo for a yearly check-up to monitor their hormone levels and make sure there haven’t been any side effects [4].

References

  1. Clifton, Merritt. (2023, June 8). No, the wait for a single-shot chemosterilant for cats has not ended. Animals 24-7. https://www.animals24-7.org/2023/06/08/no-the-wait-for-a-single-shot-chemosterilant-for-cats-has-not-ended/
  2. Crespi, S. (Producer). (2023, June 8). Contraception for cats, and taking solvents out of chemistry [Audio podcast episode]. In Science Podcast. American Association for the Advancement of Science. https://www.science.org/content/podcast/contraception-cats-and-taking-solvents-out-chemistry
  3. de Jesús, E. G. (2023, June 6). A gene therapy shot might keep cats from getting pregnant without being spayed. ScienceNews. https://www.sciencenews.org/article/gene-therapy-shot-cats-spay-pregnant
  4. Golembiewski, K. (2023, June 6). Nonsurgical cat contraception could help curb overpopulation, study says. CNN. https://www.cnn.com/2023/06/06/world/cat-contraceptives-scn/index.html
  5. Grimm, D. (2023, June 6). Hello kitty, goodbye kittens? Gene therapy spays cats without surgery. Science. doi: 10.1126/science.adj0979
  6. Katsnelson, A. (2023, June 6). Gene therapy may offer birth control for cats. The New York Times. https://www.nytimes.com/2023/06/06/science/cats-birth-control.html
  7. Ridings, M. (2023, June 6). Birth control for cats? Harvard Gazette. https://news.harvard.edu/gazette/story/2023/06/birth-control-for-cats-is-effective-but-ahead-of-its-time/
  8. Today’s Veterinary Business. (2023, June 19). Gene therapy shows promise in feline contraception. https://todaysveterinarybusiness.com/gene-therapy-0623/
  9. Vansandt, L. M., Meinsohn, M., Godin, P., Nagykery, N., et al. (2023). Durable contraception in the female domestic cat using viral-vectored delivery of a feline anti-Müllerian hormone transgene. Nature Communications, 14, 3140. https://doi.org/10.1038/s41467-023-38721-0

Published July 9th, 2023

Science

Feline Reproduction, Part II: Pregnancy and Kittens

mehshadoweye

Meredith Hemphill

mehshadoweye

Encyclopaedia Felidae now has a Patreon! Go to www.patreon.com/EncyclopaediaFelidae if you want to help support this content!

Mother tabby cat and kitten
Image by JackieLou DL from Pixabay

Happy Spring Equinox! Spring is the season of new life, and that includes new kittens. Two weeks ago, we looked at the reproductive cycles and mating behavior of cats. Now, we look at what naturally comes next. I’ll cover the stages of cat pregnancy, birth, and the basics of kitten development. Additionally, I will continue to debunk common myths about feline reproduction.

Cat Pregnancy

A she-cat carrying or raising kittens is called a queen. Queens are pregnant for approximately nine weeks (2, 5, 6, 9). About three weeks in, queens begin to show signs of pregnancy (9). This is also when it first becomes possible to confirm pregnancy because a veterinarian can then feel the kittens inside the abdomen (8, 9). An ultrasound will also do the trick (8). The symptoms of a cat pregnancy include:

  • Weight gain (4, 9)
  • Increased appetite (2, 9)
  • Dark/pink, swollen nipples (2, 4, 9)

If you have a pregnant queen on your hands, make sure to feed her food approved for “growth and reproduction” life stages. This is usually labeled as kitten food, but it has the nutrients queens need to nourish themselves and their kittens as well. As her pregnancy progresses, she will need her food delivered in frequent, small meals (8). There is less room for food in there, after all!

As a cat nears the end of her pregnancy, she begins looking for a nesting site (2, 5, 8, 9). In the wild, a queen seeks out a dry, safe, hidden, and defensible location to kit. She usually picks out several so that she has places to move her kittens if danger threatens the original nest. An indoor cat will exhibit essentially the same behavior. She may appreciate being provided with a box, basket, or bed lined with soft bedding (5, 8, 9). Or she may choose to have her kittens under the kitchen sink, or some other weird place. She will pick wherever she thinks is safest. When the time comes, cats give birth to an average of four kittens (2, 4).

Birth

When a queen is near to kitting, she will probably visit her nest site(s) repeatedly and make adjustments to the bedding (4). She may become restless or anxious (8). Queens with humans may act more affectionate and seek comfort, or do the opposite and become withdrawn (4, 9). They may meow, purr, or pant (4, 5). The queen cleans around her vulva and nipples (5). This is thought to strengthen her scent there and lay a trail for the newborn kittens to follow toward the milk supply (5). During this time contractions begin, but no kittens appear (5). This first stage of labor can last as long as 36 hours in new mothers (4).

When the queen enters the next phase of labor, the contractions strengthen and the first kitten is born (4). The placenta soon follows (4). As soon as she pushes each kitten out, the queen bites open the amniotic sac that surrounds them, licks their mouth and nose clear, and bites off the umbilical cord (4, 5). The queen eats the placentas and licks her kittens to clean them and stimulate them to breathe (4, 5). The time interval between kittens varies from ten minutes to an hour (4). Sometimes, labor may stop after one or more kittens, only to resume as much as 36 hours later to deliver the rest (4).

With the exception of some purebred cats, queens usually kit without a hitch. If you have a pregnant cat, though, make sure you know the phone number of both your veterinarian and the nearest emergency vet just in case. If you think anything seems wrong, call. Make sure you know ahead of time how many kittens to expect so you know if somebody hasn’t arrived yet. Get in touch with a vet if your queen has had contractions for more than an hour with no kitten arrival or if two hours have gone by without the next birth (8). If a kitten has been in the birth canal more than a minute or two, take your cat straight to the vet (8).

Myth #1: If you touch very young kittens, the mother cat will abandon them.

White mother cat and kittens
Image by StockSnap from Pixabay

Scent is very important to cats. There’s no doubt about that. And queens do occasionally abandon one or more kittens for a variety of reasons: the kittens may be sick, deformed, or unresponsive (3, 5). But if this is your cat and her kittens we’re talking about, there’s no need to worry about touching the kittens. Your own cat who is familiar with your scent has no reason to be alarmed at finding it on her offspring (3). It will not cause her to reject them (3). You can even move the kittens to a safer nesting site if you need to–although there’s no guarantee their mother won’t move them again somewhere she likes better (3). Try not to separate the queen and kittens for the first few days if you can help it, however (8).

Myth #2: If you spay a cat that has kittens, she’ll stop producing milk for them.

This is a common belief that sometimes causes problems for people. It makes perfect sense, but it isn’t true. A queen can go on feeding her kittens even after she’s been spayed. In fact, spayed she-cats that have never given birth will start producing milk if a kitten suckles them long enough (3). They can help surrogate orphan kittens this way (3). She-cats start going back into heat shortly after giving birth, so this misconception can be dangerous. People who think they need to leave their she-cat intact to feed her kittens may get stuck in a cycle of perpetual kitting. Nobody can find homes for that many unplanned kittens. This is a myth we really need to dispel.

Kittens

Neonate (0-2 Weeks)

Kittens are born with their eyes closed and their ears folded shut. They can barely wriggle; walking is certainly out of the question. They also can’t control their body temperature or eliminate waste on their own (1, 7). Newborn kittens rely on their mother for everything, not just food. She keeps them warm and clean, she stimulates them to urinate and defecate, and she defends them from any danger. For the first 4-5 days, neonates (from the Greek for “new” and Latin for “born”) will still have the remains of their umbilical cords attached (7). It will then fall off on its own (7). These tiny kittens weight on average 100 grams (5, 7). They can’t do much and sleep most of the time. They can purr and make distress calls, though, so they can communicate with the queen (1).

During the first week, kittens’ ears slowly start to open up (1, 7). Their eyes follow suit a couple days later (1, 7). All kittens are born with blue eyes. At the end of the first week, kittens will have doubled their birth weight (1, 5, 7). Over the course of the second week, their eyes and ears will finish opening, although their vision will take a while to reach its full potential (1, 7). Two-week-old kittens can walk a bit, but they are awfully wobbly (1, 7). Kittens this age will also start to hiss at unfamiliar scents or sounds (1). They can knead, but they cannot retract their claws yet (1).

Baby Tiger (3-5 Weeks)

A kitten’s first teeth, their incisors, come in at three weeks (1, 6, 7). They start to be able to eliminate on their own, and kittens in an indoor environment may experiment with the litter box (1, 7). They begin to be able to regulate their own body temperature as well (7). Kittens will start exploring and playing in earnest around this time (1, 6, 7).

A queen starts weaning her kittens when they are about four weeks old (5). In the wild, she also teaches them how to hunt (5). For pet cats, this is a good age to begin socializing kittens (1). Kittens at this age don’t have to be at their mother’s side every moment, so their people can start to spend some time getting them used to being handled. This is also the age when kittens’ fur coat fills out and things like markings and coat length become more apparent (1). At five weeks, a kitten’s eyesight is fully-developed, and the playtime starts to get wild (1).

Older Kitten (6-8 Weeks)

A six-week-old kitten has all of their baby teeth (7). This is typically the age when kittens are brought to the veterinarian for their first exam and vaccinations (1, 8). Kittens this age know how to clean themselves and will groom their littermates, too (1). At seven weeks, their adult eye color starts to develop (7). Some cats will keep their blue eyes, but most will change to another eye color.

At eight weeks, kittens are usually fully weaned (1, 6, 7). Kittens are sometimes adopted out at this age, as they are pretty independent from their mother. It is possible to spay/neuter kittens at eight weeks if they have reached two pounds (0.91 kg) (1, 7).

Watch Gourdon and Pepita grow up in 10 minutes! Not for those with misophonia.

Teenager (3-12 Months)

Although growth slows down a bit, a lot still has to happen before a kitten’s first year is over. They will shed their baby teeth and grow permanent ones (6). They’ll go through puberty around six months old and she-cats will have their first heat cycle (6). By that age, kittens are 80-90% of their final size (6). Teenage cats push boundaries and try new things, trying to get a sense of the world and their place in it (6). They’ll put on more muscle mass (6) and start to lose their kitten fluff. Kittens are quite fully mature at the end of their first year, but they’re almost there (6). A few more months and they’ll be all grown up (6).

Myth #3: Kittens must be six months old before they can be spayed/neutered.

It used to be the conventional wisdom that kittens needed to be six months old to be sterilized. Sometimes veterinarians may still recommend this. However, we now know that she-cats can have their first heat as early as four months old, and they can have kittens the first time they go into heat. In other words, it’s possible for a kitten to have kittens, which can lead to complications that a full-grown queen would not have. These days, it is becoming more common to instead recommend that a kitten be at least eight weeks old and at least two pounds (0.91 kg) to be sterilized (1, 6, 7). This prevents a lot more unwanted heat cycles and pregnancies.

Works Cited

  1. Alley Cat Allies. (n.d.). How old is that kitten? Kitten progression: At-a-glance. Alleycat.org. https://www.alleycat.org/resources/kitten-progression/
  2. Bukowski, J. A. and Aiello, S. (2011, July). Breeding and reproduction of cats. Merck Veterinary Manual. https://www.merckvetmanual.com/cat-owners/routine-care-and-breeding-of-cats/breeding-and-reproduction-of-cats
  3. E-staff. (2007, June 21). Mothering myths & truths. CatWatch. Retrieved from https://www.catwatchnewsletter.com/features/mothering-myths-truths/
  4. International Cat Care. (2018, July 31). Cat birth. https://icatcare.org/advice/cat-birth/
  5. International Cat Care. (2018, July 31). Cat pregnancy. https://icatcare.org/advice/cat-pregnancy/
  6. Moore, A. (2001). The kitten owner’s manual. Storey Publishing: North Adams, Massachusetts.
  7. Shaw, H. (n.d.). Determining a kitten’s age. Kitten Lady. http://www.kittenlady.org/age
  8. Stregowski, J. (2020, October 17). How to care for a pregnant cat. The Spruce Pets. https://www.thesprucepets.com/care-of-a-pregnant-cat-555417
  9. Syufy, F. (2019, October 22). Cat pregnancy stages. The Spruce Pets. https://www.thesprucepets.com/cat-pregnancy-stages-555411

Published March 21, 2021