Lab study, 2002
How does the body trigger menstrual bleeding?
A molecule called LEFTY-A plays a key role by increasing dramatically before your period and triggering breakdown of the womb lining. Progesterone normally stops this from happening.
What they did
They measured LEFTY-A levels in the womb lining at different points in the cycle. They also removed hormones from womb tissue in the lab and watched what happened. Then they added progesterone back to see if it stopped these changes.
What they found
LEFTY-A levels increased approximately 100-fold just before the period. When hormones were removed, LEFTY-A increased and triggered production of tissue-breaking enzymes. Progesterone blocked both the increase in LEFTY-A and its effects on these enzymes.
What it means for you
LEFTY-A is a local signal that tells your womb lining to break down before your period, and progesterone is the master control that stops this. This helps explain how progesterone keeps pregnancy going by preventing menstruation. The main limitation is that this study was done in womb tissue in the lab, so we do not know all the details of how it works in living women.
100-fold
increase in LEFTY-A at perimenstrual phase
About the study
- Original title
- Regulation and function of LEFTY-A/EBAF in the human endometrium. mRNA expression during the menstrual cycle, control by progesterone, and effect on matrix metalloprotineases
- Authors
- Cornet PB, Picquet C, Lemoine P et al.
- Journal
- The Journal of biological chemistry
- Year
- 2002
- Study design
- Lab study
- What was tested
- Removal and addition of ovarian hormones in womb tissue samples.
- Open access
- Yes
- Read the paper
- doi.org/10.1074/jbc.m201793200
Original abstract
The human endometrium is a unique tissue that is periodically shed during menstruation. Although overall triggered by ovarian steroids withdrawal, menstrual induction of matrix metalloproteinases (MMPs) and resulting tissue breakdown are focal responses, pointing to additional local modulators. LEFTY-A, a novel member of the transforming growth factor-beta family identified originally as an endometrial bleeding-associated factor (EBAF), is a candidate for this local control. We measured LEFTY-A and beta-ACTIN mRNA concentration during the menstrual cycle in vivo and found that their ratio was dramatically ( approximately 100-fold) increased at the perimenstrual phase. A similar increase was seen when proliferative explants were cultured for 24 h in the absence of ovarian steroids; this was followed by spontaneous production of proMMP-1, -3, and -9. Both responses were inhibited by progesterone. Moreover, addition of recombinant LEFTY-A to proliferative explants was sufficient to stimulate the expression of proMMP-3 and -7; this response was also blocked by ovarian steroids. Collectively, these data indicate that LEFTY-A may provide a crucial signal for endometrial breakdown and bleeding by triggering expression of several MMPs. Progesterone appears to exert a dual block, upstream by inhibiting LEFTY-A expression and downstream by suppressing its stimulatory effect on MMPs.
Reproduced under CC-BY.