Can women generate oocytes late into life?

You remember what you learned in biology right -- or maybe health. A woman is born with all the eggs she will ever have. Well some researchers in Australia are disputing that point.

By doing stereology on mice aged 1 to 200 days they claim to show that the overall number of eggs does not decline. Stereology is the science of accurately counting cells in a tissue.

The trouble is that I don't buy it.

Here is the abstract (the article requires a subscription):

Proliferation and partial meiotic maturation of germ cells in fetal ovaries is believed to establish a finite, non-renewable pool of primordial follicles at birth. The supply of primordial follicles in postnatal life should be depleted during folliculogenesis, either undergoing atresia or surviving to ovulation. Recent studies of mouse ovaries propose that intra- and extraovarian germline stem cells replenish oocytes and form new primordial follicles. We quantified all healthy follicles in C57BL/6 mouse ovaries from day 1 to 200 using unbiased stereological methods, immunolabelling of oocyte meiosis (germ cell nuclear antigen (GCNA)) and ovarian cell proliferation (proliferating cell nuclear antigen (PCNA)) and electronmicroscopy. Day 1 ovaries contained 7924+/-1564 (s.e.m.) oocytes or primordial follicles, declining on day 7 to 1987+/-203, with 200-800 oocytes ejected from individual ovaries on that day and day 12. Discarded oocytes and those subjacent to the surface epithelium were GCNA-positive indicating their incomplete meiotic maturation. From day 7 to 100 mean numbers of primordial follicles per ovary were not significantly depleted but declined at 200 days to 254+/-71. Mean numbers of all healthy follicles per ovary were not significantly different from day 7 to 100 (range 2332+/-349-3007+/-322). Primordial follicle oocytes were PCNA-negative. Occasional unidentified cells were PCNA-positive with mitotic figures observed in the cortex of day 1 and 12 ovaries. Although we found no evidence for ovarian germline stem cells, our data support the hypothesis of postnatal follicle renewal in postnatal and adult ovaries of C57BL/6 mice.

Here is my question. How do you know that the mouse you dissected at day 200 didn't have a bunch more follicles to begin with? It seems like the range in the number of follicles is very large to begin with so I it would be hard to infer that this particular mouse did not have a declining number of follicles. I don't think that stereology is going to be able to answer this question. They claim to observe dividing cortical cells, but that I also don't buy because there is no way to be certain that those were the egg producing cells rather than another cell type.

The trouble is that I am not certain how else I would test this problem. How could you try and observe eggs being created over an individual animals lifetime? Maybe you could take one ovary out at one point, and another at another. Or maybe biopsies.

This point is not unrelated to neuroscience if you remember the huge fuss that was adult neurogenesis. Demonstrating that a cell type is increasing or decreasing in a living animal is a tricky business.

This is also a cautionary tale on overly bullish press releases. Get this:

In research that could have broad implications for women's fertility treatments, scientists have found that despite their age, female mice have a renewable egg supply in their ovaries.

The discovery, by Professor Jock Findlay from Prince Henry's Institute and Associate Professor Jeff Kerr from Monash's Department of Anatomy and Cell Biology, has sparked controversy among biologists and challenged the theory, held for more than 50 years, that female mammals are born with a finite number of oocytes (eggs).

Two years ago, international researchers speculated that mice could continue to produce eggs throughout puberty and adulthood. Although their speculation caused debate throughout the scientific community, the scientists could not produce evidence to confirm their idea. However, Professor Findlay and Dr Kerr's research gives support to the theory. Their findings have been published in the July issue of Reproduction.

I know that people want to work up enthusiasm, but I love how contreversy in science somehow is always magically transmuted into accurary in a press release. It is like the more off the wall an idea is the more likely a press release will be to claim its absolute relevance and accuracy.

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You miss the point - the big papers came out a couple of months ago. In the first paper a bone marrow from a GFP expressing mouse was transplanted into a native mouse. The native mouse developed GFP expressing oocytes (after ovary dissection). In paper #2 a second group fused the blood systems of a GFP mouse with that of a native mouse but FAILED to see any ovulated eggs expressing GFP in the native mouse (or native eggs in the GFP mouse). So the field is in turmoil.

The newest manuscript gives support to the de novo model, but in itself is not the bulk of the evidence for this theory.

If you remember, Wagers also did a parabiosis experiment to challenge some of the claims of the adult stem cell field (which sparked a fight between Diane Krause and Irving Weissman in Science letters at the time). There is clearly something different between the bone marrow replacement model, and parabiosis, in which the blood is shared but without irradiation and transplantation of large numbers of HSC.

You could test it statistically. Get a statistically large enough number of similar mice and randomly sort them into two or more bins. Dissect one group at time 'a', the next group at time 'b', etc, and plot the mean number of oocytes (plus error bars) at each time to get a trend.

By King Aardvark (not verified) on 10 Jul 2006 #permalink