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Pregnancy Timeline by SemestersDevelopmental TimelineFertilizationFirst TrimesterSecond TrimesterThird TrimesterFirst Thin Layer of Skin AppearsEnd of Embryonic PeriodEnd of Embryonic PeriodFemale Reproductive SystemBeginning Cerebral HemispheresA Four Chambered HeartFirst Detectable Brain WavesThe Appearance of SomitesBasic Brain Structure in PlaceHeartbeat can be detectedHeartbeat can be detectedFinger and toe prints appearFinger and toe prints appearFetal sexual organs visibleBrown fat surrounds lymphatic systemBone marrow starts making blood cellsBone marrow starts making blood cellsInner Ear Bones HardenSensory brain waves begin to activateSensory brain waves begin to activateFetal liver is producing blood cellsBrain convolutions beginBrain convolutions beginImmune system beginningWhite fat begins to be madeHead may position into pelvisWhite fat begins to be madePeriod of rapid brain growthFull TermHead may position into pelvisImmune system beginningLungs begin to produce surfactant
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Is there a 'mother's curse' ?

There is new evidence that "the mother's curse", or a moms' ability to transmit genes that harm her sons — but not her daughters, holds true in all animals.

The "curse" exists because there are two independent sources of genetic information within our bodies. One is the genome, all eukaryotes — eukaryotic cells are plant and animal cells surrounded by a membrane — have the largest portion of genes in the nucleus of each cell. However, a much smaller gene legacy is located in our mitochondria — small, bean shaped structures processing oxygen into energy; the only places in the cell where oxygen is reduced and eventually broken down into water.

These two parts of the genome fight a continual "molecular arms race" that impacts the health of every organism they inhabit.

Unlike the nuclear genome, which is built from a combination of both father and mother gene codes, the mitochondrial genome is passed exclusively from the mother to her female children. As a result, male offspring are at an evolutionary dead end.

Natural selection actively suppresses mutations in female mitochondrial DNA (mtDNA), but there is no weeding out or replacement of weak genes in males - as there are no back up male mitochondrial genes. It is generally accepted that human mitochondria were once, billions of years ago, independent bacteria swimming in a vast sea. They somehow became absorbed into another single celled creature and then figured out how to use oxygen from that co-mingling for their own energy needs. Eukaryotes still do not have the ability to use oxygen without mitochondria. So, those early sinlgle cell life forms that found they could swallow early mitochondrial ancestors, without digesting them, gave themselves the use of oxygen which continues to expand the length and versatility of our own lives.

Eukaryotic cells bsorbing mitochondria whole, converted
them into an "endosymbiont" — an organism capable
of living within the body of another organism.

Thus, mitochondria can be found in every area of the body with an intense need for oxygen — such as in all muscle tissues, including our heart. According to John Allen, a biologist at University College London not involved in this study: “...that’s a very fundamental feedback mechanism.” Mitochondria produce proteins right where they’re needed which better regulates energy production. Although other cell structures could benefit from this type of local control, only mitochondria have their own command center.

Now, a team of biologists at Vanderbilt University and the Fred Hutchinson Cancer Research Center in Seattle, have discovered mutant mtDNA in the fruit fly Drosophila melanogaster supporting the mother's curse theory in all animals.

Mitochondria reduce male fertility as males age,
with no observable affects on female siblings.

Explains Maulik Patel PhD, assistant professor of biological sciences at Vanderbilt, and head of the study: "In the 20 years since this possibility was recognized, a few mitochondrial mutants have been reported that have deleterious effects on male offspring. But, none convincingly showed the mutation negatively affecting females. Our study is the first to look comprehensively for the effects of male-harming mtDNA mutants on females. We were fortunate to find one mutation that has a negative impact on male offspring without having any adverse affects on female siblings."

Their discovery is described in an article published online Aug. 2 in the journal eLife.

The "mothers curse" is one of the more bizarre consequences of natural selection. According to evolutionary theory, mitochondrial DNA (mtDNA) and nuclear DNA are locked in an unending competition. As one accumulates beneficial mutations, then the other is forced to adapt. This is known as the "Red Queen hypothesis," taken from "Through the Looking Glass" written by Lewis Carroll and spoken by the Red Queen: "...it takes all the running you can do, to keep in the same place."

Plants have much larger mitochondrial genomes containing larger numbers of genes. In plants, striking instances of male-harming mitochondria already have been discovered. As the mitochondrial genome in animals is much smaller, it makes it much harder to detect similar male-harming mutations.

The experiment that ultimately discovered male-harming mtDNA mutations took more than four years to complete. Scientists set up 18 independent lines of fruit flies, each with 300 females and 100 males. In 12 of these lines, virgin females were collected in each generation and mated with males from the original stock. Researchers did this for 35 generations (or 70 weeks). In the remaining six lines, females were allowed to mate with sibling males of their choice. Throughout this time, researchers monitored individual fly fitness to determine whether males were in someway harmed. When they were done, Patel along with Miriyala and Littleton (research technicians at the Hutchinson Center) found that a single-point mtDNA mutant had taken over only one of the fruit fly lines.

Analysis of this mtDNA mutation produced a single amino-acid change in the chemical structure of a subunit of an enzyme called cytochrome C oxidase. This mutation was determined to be the cause of premature lower sperm production and sperm motility in males as they age.

"We weren't looking specifically for mutations that affect fertility, but, in retrospect, it makes sense.

"Mutations that affect males, but not females, must be affecting male and female tissues differently."

Maulik Patel PhD, Assistant Professor, Biological Sciences, Vanderbilt University, and head of the study. The research was conducted in the laboratory of evolutionary biologist Harmit Singh Malik PhD, the Fred Hutchinson Cancer Research Center.

Their findings explain the relationship between mutant human mtDNA and slow sperm motility in 7 to 10 percent of men — mtDNA mutations may significantly be contributing to male sub-fertility.

Research also discovered that the mutated
enzyme is temperature sensitive.

Turning up cage temperature by four degrees Celsius caused male mice carrying the mutation to become almost completely sterile. This allowed the scientists to test a second prediction of the mother's curse hypothesis: the nuclear genome can evolve mechanisms suppressing male-harming mtDNA mutations and restore male fitness.

They mated females with mutant mtDNA to males from different fruit fly strains collected from around the world. Then they assayed the male offspring's fertility and were surprised to discover that nuclear genomes from many of these strains had completely restored male fertility.

"Our strategy used in this study, combined with advances in manipulating mitochondrial genomes, provides exciting opportunities to explore the 'dark side' of one of the oldest and most important symbioses [endosymbiont] on the planet.

"We hope this will lead to ways to treat mitochondrial diseases, only a few which currently can be treated, and which are inherited by one newborn in every 200 to become manifest in about one adult out of 5,000,"

Maulik Patel PhD.

Due to their strict maternal inheritance in most animals and plants, mitochondrial genomes are predicted to accumulate mutations that are beneficial or neutral in females but harmful in males. Although a few male-harming mtDNA mutations have been identified, consistent with this ‘Mother’s Curse’, their effect on females has been largely unexplored. Here, we identify COIIG177S, a mtDNA hypomorph of cytochrome oxidase II, which specifically impairs male fertility due to defects in sperm development and function without impairing other male or female functions. COIIG177S represents one of the clearest examples of a ‘male-harming’ mtDNA mutation in animals and suggest that the hypomorphic mtDNA mutations like COIIG177S might specifically impair male gametogenesis. Intriguingly, some D. melanogaster nuclear genetic backgrounds can fully rescue COIIG177S -associated sterility, consistent with previously proposed models that nuclear genomes can regulate the phenotypic manifestation of mtDNA mutations.

DOI: http://dx.doi.org/10.7554/eLife.16923.001

In addition to Patel, Miriyala and Littleton, co-authors of paper include Janet Young from the Fred Hutchinson Cancer Research Center, Hieko Yang andYukiko Yamashita from the University of Michigan, Kien Trinh, Scott Kennedyand Leo Pallanck from the University of Washington. The research was conducted in the laboratory of evolutionary biologist Harmit Singh Malik at the Fred Hutchinson Cancer Research Center.

The research was supported by grants from the Helen Hay Whitney Foundation, the Mathers Foundation and National Institute of Health grants F30 AG045021, GM104990 and GM074108.
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Aug 12, 2016   Fetal Timeline   Maternal Timeline   News   News Archive   

mitochondrial damage

Mitochondrial DNA damage (RIGHT).
Image Credit:
Global Research



Phospholid by Wikipedia