By Carol Beuchat PhD
Every trait of an animal must be the result of two things: genetics and environment. In this context "environment" includes anything and everything that is not genetic. So, if there is a particular trait or disorder in a dog, we can do some pedigree or labratory research to determine if it is caused by a genes.
When affordable canine DNA testing appeared on the scene about a decade ago, there was a flood of studies identifying the normal genetic variants or mutations associated with particular traits and disorders and traits. We quickly identified a slew of single-gene causes for all sorts of things, and for a short time it was like picking the low-hanging fruit off a tree.
Then the new discoveries started to dry up. More studies identified not one but many potentially-associated variants, none of which was simply causal, and breeders were left without clear answers and the inability to select against traits based on presence of absence of a single gene. Identification of new mutations slowed, and breeders were left with tough choices - remove an animal from the breeding pool if it's afflicted with a disorder, along with its parents, offspring, and relatives, or cross your fingers and breed to an (apparently) unaffected dog. There are many problems that fall into this category - epilepsy, cancer, renal dysplasia, neurological and heart disorders, and many more. These are often tragic, expensive to treat, and result in death at a young age.
But the genetic studies continue and fuel hope of identifying a gene breeders can test for, despite the fact that we already suspect a polygenic basis.
Then the new discoveries started to dry up. More studies identified not one but many potentially-associated variants, none of which was simply causal, and breeders were left without clear answers and the inability to select against traits based on presence of absence of a single gene. Identification of new mutations slowed, and breeders were left with tough choices - remove an animal from the breeding pool if it's afflicted with a disorder, along with its parents, offspring, and relatives, or cross your fingers and breed to an (apparently) unaffected dog. There are many problems that fall into this category - epilepsy, cancer, renal dysplasia, neurological and heart disorders, and many more. These are often tragic, expensive to treat, and result in death at a young age.
But the genetic studies continue and fuel hope of identifying a gene breeders can test for, despite the fact that we already suspect a polygenic basis.
We know that a trait or disease must be the consequence of genes, environment (non-genetic factors), or both. The heritability of a trait or disease can be computed from a pedigree database; this tells us the fraction of variation in a trait that can be accounted for by genetics and, from our simple relationship described above, the rest of the variation in a trait must be due to environment.
When we fail to find a strong genetic basis for a trait or disorder, step two should be identifying the potential environmental factors that are causing variation.
Unfortunately, we rarely do this. In fact, we rarely estimate heritability, which would tell us something about the relative contributions of genes and environment. If 20% of the variation in a trait is accounted for by genetics, we know that something other than genetics is accounts for the rest of the variation. Many, many health disorders have relatively low heritability, on the order of 10% to 35%.
Maybe we should focus on identifying the some of the environmental factors that account for a huge chunk - 70-90% - of the variation among animals in a trait?
Unfortunately, we rarely do this. In fact, we rarely estimate heritability, which would tell us something about the relative contributions of genes and environment. If 20% of the variation in a trait is accounted for by genetics, we know that something other than genetics is accounts for the rest of the variation. Many, many health disorders have relatively low heritability, on the order of 10% to 35%.
Maybe we should focus on identifying the some of the environmental factors that account for a huge chunk - 70-90% - of the variation among animals in a trait?
We have lots of ideas about what non-genetic factors could be responsible for the many disorders in dogs that lack a good genetic explanation. Environmental toxins, flea and tick treatments, highly processed kibble, and many more things have been proposed but rarely pan out as the cause of a problem. We are left empty handed continue to cope with health issues that we are powerless to solve.
I've been worrying about this problem for long time, and I didn't have any better ideas than anybody else.
But as part of a project, I monitored the whelping of dozens of litters of puppies of all breeds, and I was stuck by what I considered an astonishing number of puppies that were perfectly formed but dead on arrival, as well as the many that were extremely distressed at birth, often with fluid in the airways, including some with no signs of life - not breathing, no heartbeat - but were brought back to life with vigorous efforts by the breeder.
This seemed to be a "normal" thing experienced by many breeders, and attributed to bad luck, or maybe a virus, or something that remained unidentifies.
My thought as a biologist trying to make sense of the outrageous levels of morbitity and mortality in perinatal puppies was that this couldn't possibly be how "the dog" produced puppies, with high mortality that appears to be the result of an event that occurs in the short period of time between detachment of the placenta and expelling from the birth canal. I needed to figure out what was going on here.
But as part of a project, I monitored the whelping of dozens of litters of puppies of all breeds, and I was stuck by what I considered an astonishing number of puppies that were perfectly formed but dead on arrival, as well as the many that were extremely distressed at birth, often with fluid in the airways, including some with no signs of life - not breathing, no heartbeat - but were brought back to life with vigorous efforts by the breeder.
This seemed to be a "normal" thing experienced by many breeders, and attributed to bad luck, or maybe a virus, or something that remained unidentifies.
My thought as a biologist trying to make sense of the outrageous levels of morbitity and mortality in perinatal puppies was that this couldn't possibly be how "the dog" produced puppies, with high mortality that appears to be the result of an event that occurs in the short period of time between detachment of the placenta and expelling from the birth canal. I needed to figure out what was going on here.
A puppy that is still enclosed in a fluid-filled sack and only partially expelled from the birth canal.
A few years later, I think I have an answer that, surprisingly, was hiding in plain sight.
A 2001 PhD thesis looked at causes of mortality in newborn puppies and found that the puppies simply run out of oxygen before they make it into the real world. Once the placenta detaches from the uterus, the oxygen supply for the puppy is limited. If the puppy is not born before its oxygen is depleted, it becomes hypoxic (low blood oxygen concentration), and simply suffocates. The result is stillborn puppies, or puppies that try to breathe before they are born and instead of air, inhale fluid.
A 2001 PhD thesis looked at causes of mortality in newborn puppies and found that the puppies simply run out of oxygen before they make it into the real world. Once the placenta detaches from the uterus, the oxygen supply for the puppy is limited. If the puppy is not born before its oxygen is depleted, it becomes hypoxic (low blood oxygen concentration), and simply suffocates. The result is stillborn puppies, or puppies that try to breathe before they are born and instead of air, inhale fluid.
But why are they running out of air? Because birth is too slow.
As every breeder knows, whelping can be quick, with new puppies appearing every few minutes. Or it can take many hours, sometimes with hours between births. There can be lots of straining by the bitch yet puppies are produed very slowly, sometimes even with a puppy making a partial appearance, still encased by membranes and fluid, when the contraction wasn't strong enough to expel the puppy completely.
Slow whelping is caused by uterine inertia, in which the strength of uterine contractions are not strong enough to expel the puppies. Several studies have looked for a cause for uterine inertia, suggesting things like age or pariety of the bitch, litter size either too large or too small, even exhaustion of the bitch. But none of these was an adequate explanation.
As every breeder knows, whelping can be quick, with new puppies appearing every few minutes. Or it can take many hours, sometimes with hours between births. There can be lots of straining by the bitch yet puppies are produed very slowly, sometimes even with a puppy making a partial appearance, still encased by membranes and fluid, when the contraction wasn't strong enough to expel the puppy completely.
Slow whelping is caused by uterine inertia, in which the strength of uterine contractions are not strong enough to expel the puppies. Several studies have looked for a cause for uterine inertia, suggesting things like age or pariety of the bitch, litter size either too large or too small, even exhaustion of the bitch. But none of these was an adequate explanation.
So here's the mystery. We have hundreds of heath disorders in dogs for which we have no clear genetic explanation. We also have a high attrition rate of newborn puppies attributed to uterine inertia. Could these things be related? What environmental factor (again, meaning non-genetic) could explain these things that would also be common to dogs of many breeds from all over the world, and that affected dogs produced by millions of breeders? It was a real puzzle.
Digging around in the pediatric literature, I finally connected the dots. The strength of uterine contractions during childbirth depends on the presence of the hormone melatonin, which interacts with oxytocin to increase the strength of uterine contraction. As you might know, melatonin is called the "sleep hormone" because it is secreted only at night. Secretion in the daytime is blocked by light, so your melatonin levels are low during the daytime and rise at night.
So, if you were going to give birth to a baby - or a litter of puppies - the most likely time for it to happen is in the darkness of night. Indeed, most infants are born between 1:00 AM and 7:00 AM, with the peak at about 4:00 AM.
Connecting these dots was easy. Uterine inertia in dogs could be caused by inadequate melatonin. If the whelping box is set up in the house where there is adequate light for the breeder to keep an eye on things, the bitch's melatonin would likely be suppressed, resulting in uterine inertia and puppies that run out of oxygen before they are born. If breeders are monitoring the progress of labor, the ambient light will block the secretion of melatonin, resulting in puppies that are hypoxic or even stillborn.
Breeders closely monitor whelping so they can assist when necessary and make sure the newborns are all breathing and connecting to the food supply. But it's probably the lights that are causing the stillbirths and distress of the newborns. Mom's melatonin secretion depends on nighttime darkness. When we turn on the lights, we block the very hormone necessary for strong contractions that will expell puppies quickly.
The connections among the dots here are compelling and offer a sensible explanation for the uterine inertia and high attrition of newborn puppies. I'm beginning a study working with breeders that want to do what I'm calling "dark whelping", for which we eliminate ALL light from the whelping room and document the whelping of the puppies and behavior of the dam. By trial and error, we have found that even a very - VERY - tiny bit of light will shut down uterine contractions, so we are whelping in total darkness. With infrared video cameras, we can watch from outside the room and not miss a thing. And surprisingly, the maternal behavior of the dam seems better in total darkness; no growling or nipping at puppies, no reluctance to nurse or stay in the box, none of the issues with mom that can be a nightmare for the exhausted breeder to manage. In the dark, mom handles everthing competently with no assistance needed. After the video is set up, the breeder and I can settle down with wine and cheese and just watch the show on a phone or tablet.
If you're expecting a itter and are interested in participating in this project, just drop me a note and we can arrange it!
If you're expecting a itter and are interested in participating in this project, just drop me a note and we can arrange it!
But we haven't settled the other problem we were worrying about - the high rate of apparently non-genetic disorders in dogs. We needed to find an environmental cause that wouldn't be limited to a narrow group of dogs, like a particular brand of flea treatment or kibble. We needed something that is probably "global".
I think the cause could be the way we are whelping our puppies - under lights for observation, instead of in the dark or at night, which results in uterine inertia and slow whelping. What's the connection here?
I think the cause could be the way we are whelping our puppies - under lights for observation, instead of in the dark or at night, which results in uterine inertia and slow whelping. What's the connection here?
We can reasonably expect that inadequate oxygen during birth is going to be a problem for dogs. We certainly know that babies that are deprived of adequate oxygen during birth, even very briefly, can be left with a long list of deficiencies and disorders, many of which can compromise health over the lifetime, and some of which are fatal. This is well-documented in the pediatric literature.
These tables list some of the disorders associated with free radical damage cause by oxygen stress during birth in humans, both in newborns and over the lifespan. Some of these are problems in dogs as well - arthritis, cancer, cataracts, heart failure, inflammatory bowel disease, neurological disorders, and a variety of ther things.
These tables list some of the disorders associated with free radical damage cause by oxygen stress during birth in humans, both in newborns and over the lifespan. Some of these are problems in dogs as well - arthritis, cancer, cataracts, heart failure, inflammatory bowel disease, neurological disorders, and a variety of ther things.
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Although we should expect that oxygen deprivation during birth could result in similar deficits in dogs, this has received surprisingly little attention. Oxygen deprivation during birth is exactly the sort of non-genetic insult we are looking for to account for the non-genetic sources of health issues is dogs. It is not breed-specific, not limited to only some areas in the world, and - most importantly - not identified by breeders as problem during whelping that can have health consequences not just in the neonata puppy, but for over a lifetime. It's a cause of a huge problem that is literally hiding in plain sight.
Stillborn puppies and pups that are distressed at birth are attributed to bad luck and accepted as a part of the normal emotional burden of being a breeder. But if we undertstand the biology of melatonin and its critical role in the process of whelping, we would recognize this as an exestential problem of our own making and one that is relatively easy to solve.
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Light has many effects on reproduction processes, even beyond the ones described here for melatonin. Breeders are largely unaware of these, so they are overlooked while we tend to focus on identifying genetic causes for health problems. It is critical that we broaden our perspective when trying to address health issues, and breeders should be encouraged to expand their education to include understand the many ways non-genetic factors could be responsible for some of the health problems in dogs.
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READ THIS!
There is no research documenting the effects of administered melatonin in pregnant dogs and nothing about dosage or timing. DO NOT GIVE YOUR PREGNANT BITCH MELATONIN EXCEPT UNDER THE SUPERVISION OF A VETERINARIAN FAMILIAR WITH ITS ROLE IN WHELPING!! |
To this end, I am deveoping a program to evaluate whelping in total darkness with the cooperation of breeders that are expecting a litter soon. If you would like to contribute to the project, please join the Facebook group for the project at -
https://www.facebook.com/groups/uterineinertiaindogs
You can also enroll in the NEW ICB Course about dark whelping and other effects of light on canine physiology: "From Breeding To Weaning: The Critical Role Of Light". The course starts on 13 May with recorded live lectures that you can access at any time.
https://www.facebook.com/groups/uterineinertiaindogs
You can also enroll in the NEW ICB Course about dark whelping and other effects of light on canine physiology: "From Breeding To Weaning: The Critical Role Of Light". The course starts on 13 May with recorded live lectures that you can access at any time.
You can learn more about the course and register here -
https://www.instituteofcaninebiology.org/breedingtoweaning.html
https://www.instituteofcaninebiology.org/breedingtoweaning.html
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