What Triggers Birth in Mammals?

I was reminded of my post from 31 August 2013 on the length of pregnancy and on animals which synchronise the onset of parturition when I read the Biographical Memoir written by Peter Gluckman and Tatjana Buklijas on ‘Mont’ Liggins*. Liggins set off a whole train of research from the 1960s onwards on the control of the onset of parturition by finding that, in sheep, the fetus provides the trigger for parturition through activation of the hypophysio-adrenocortical axis and the production of glucocorticoid. Gluckman and Buklijas describe Liggins’s discoveries very well in the context of all that was happening in research on the fetus and to who was doing what, where and why.

I kept a close eye on research on the control of the onset of parturition throughout the 1970s and 80s, in view of the link between parturition and the onset of copious milk secretion which we termed ‘lactogenesis stageII’†. It was soon obvious that, and quoting from Liggins and Buklijas, …there was no shared mechanism controlling the onset of labour across the entire eutherian clade. In some species, such as mice, goats and rabbits, the maintenance of pregnancy depended on the persistence of corpus luteum to the end, and a decrease in progesterone levels signalled the onset of labour. In other species—sheep, cows and primates including humans—the placenta took over the role of the corpus luteum, so these species were termed ‘placentally dependent’, yet even this group was far from homogeneous, with sheep and cows showing much clearer evidence of a marked hormonal change preceding parturition than did primates.

A number of large teams throughout the world, including a number of personal friends, have been working on the control of parturition in the decades following Liggins discoveries, both in collaboration and competition. However, I was surprised to find that there is a stark truth. Returning to the Biographical Memoir:

Writing in the 1990s, Liggins summed up the results of the decades of research into the physiology of human parturition: first, rather than either the fetus or the mother occupying the leading role, the mechanism involved an interaction between the two participants, fetus (chorion) and mother (decidua); and second, the synthesis and release of prostaglandin F2α from decidua was a key event in the onset of parturition. Little has changed since that time, although we now know much more about the complex paracrine interactions between the amnion, decidua and chorion in driving this process and of the possible role of placental corticotrophin-releasing factor.

In short, we still do not know the trigger for parturition in any species or indeed whether there is a single trigger in a particular species. Those animals that synchronise parturition, like the wildebeest and banded mongoose, provide an intriguing glimpse into control mechanisms that, as far as I am aware, has not yet been exploited.

I end on a large ‘phew’. The link between parturition and lactogenesis stage II is much simpler.

Wildebeest (Connochaetes taurinus). Masai Mara, Kenya, 1991

*Gluckman, P., Buklijas, T. 2013. Sir Graham Collingwood (Mont) Liggins. 24 June 1926 — 24 August 2010. Biographical Memoirs of Fellows of the Royal Society 59, 195-214.

†Fleet, I.R., Goode, J.A., Hamon, M.H., Laurie, M.S., Linzell, J.L., Peaker, M. 1975. Secretory activity of goat mammary glands during pregnancy and the onset of lactation. Journal of Physiology 252, 763-773.

Human Pregnancy: Gestation Period Variation Compared with Nanny Goats

One of the stories running during this year’s ‘silly season’, when news media are desperately trying to fill newspapers, radio, television and websites, was one highlighting research¹ which showed, in the words of the BBC News website, Pregnancy length “varies naturally by up to five weeks”.

Great surprise was expressed about this range of variation (14% of the mean ovulation to delivery period of 268 days). In practical terms the sheer stupidity of giving expectant mothers a ‘due date’ (with the implication that being ‘overdue’ is abnormal) was highlighted. In these days where education in biological systems has declined to the extent that the public expect certainty in all things biological and medical, the reports helped to highlight that variation and uncertainty are to be expected.

Reading of the extent of the variation, I tried to remember the variation I had found in the goat. In 1978 I collected all the data from the then goat herd at what is now the Babraham Institute that had been recorded between 1954 and 1977, a total of 374 cases². The mean time between mating and delivery was 150 days (as also found by Sydney Arthur Asdell in 1929). Although 90% of births occurred between 146 and 154 days, the full range was 135-159 days (24 days). The percentage variation (24/150) of 16 is very similar to the latest human data.

So, if we have 14% variation for the human gestation period and 16% for the caprine, what about other mammals? A quick look through a UFAW Handbook and elsewhere suggests a similar level of variation (cat 14%, dog 13%, rabbit 22%, guinea pig 11%, rat 14%). Somebody must have noted this before somewhere but if they have I cannot remember it nor can find reference to it.

Is the variation in the length of pregnancy the simple result in differences in the rate of development of the fetus? Or adaptive in that the time of parturition can be controlled? Or both?

As work on the initiation of parturition by activation of the fetal adrenal developed during the 1970s, the talk in the coffee room was that fetal control of the onset could not be the whole story since some herd animals clearly synchronised parturition in addition to synchronising oestrus. Wildebeest were the prime example. The extent of the control is illustrated by Berger’s studies on American Bison³. Gestation was shorter by approximately 6 days in those females that mated after the seasonal peak, thereby ensuring that births were synchronised with the females that had mated at the peak. There was a difference in whether or not the females were in good body condition. Gestation was earlier in those in good condition but not in those in poor condition. Clearly though there is an advantage in ensuring that births are synchronised since delivering early came with a cost. The tradeoff was that the offspring of those females that delivered early were approximately 20 kg lighter when 6 months old. Achieving synchrony, presumably to lessen the chances of predation, is clearly an important reproductive tactic. But are we any the wiser now as to the physiological mechanism of this control than we were in the mid-1970s?

Finally, is there any evidence of adaptive control of the onset of parturition in human mothers? I know of no evidence, only of all sorts of attempts to get things moving. I have seen the exertion of ascending the Peak in Hong Kong along Hatton Road as one try; the eating of a very large roast-beef dinner as another. Did they work? Well, the babies appeared eventually.

¹ Jukic, A.M., Baird, D.D., Weinberg, C.R., McConnhaughey, D.R. & Wilcox, A.J. 2013. Length of human pregnancy and contributors to its natural variation. Human Reproduction doi:10.1093/humrep/det297

² Peaker, M. 1978. Gestation period and litter size in the goat. British Veterinary Journal 134, 379-383.

³ Berger, J. 1992. Facilitation of Reproductive Synchrony by Gestation Adjustment in Gregarious Mammals: A New Hypothesis. Ecology 73, 323-329.