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Medical researchers at Imperial College London have discovered an enzyme that may explain both miscarriage and infertility. Treatments that regulate production of the enzyme may provide ways for women to control their fertility without hormone treatments.

Scientists Discover Gene That May Be Responsible for Both Miscarriage and Infertility

The enzyme, known as serine-threonine protein kinase-1, or SGK1, regulates flows sodium and potassium into cells all over the body. When sodium flows into a cell, water flows in. The cell swells, and tissues made of similarly acting cells also swell. When SGK1 is not sufficiently active, tissues may be flat and unresponsive to hormonal stimulation. When SGK1 is overactive, tissues may be swollen and overly responsive to hormonal stimulation.
Women who have excessive production of this enzyme tend to miscarry and women who have deficient production of this enzyme tend not to be able to get pregnant.

The Link Between SGK1 and Women's Fertility

Women during their childbearing years undergo a menstrual cycle that prepares the uterus for the possibility of fertilizing 1 (or occasionally more) of the approximately 450 eggs in her ovaries. The uterus builds up its lining during the first half of menstruation, known as the follicular phase. Estrogen levels peak just before the release of the egg or eggs from one of the ovaries at ovulation.

If the egg is fertilized within about 24 hours of its release, it may be fertilized and start to form an embryo. The embryo is then implanted in the prepared lining of the womb. If fertilization and implantation do not occur, the uterus responds to increasing amounts of progesterone and "dries out" so it can be sloughed off with blood and cervical fluid during menstruation, and the cycle starts over again.

SGK1 regulates the sensitivity of the uterus to progesterone. The more of the SGK1 enzyme that is produced by the lining of the cells of the uterus, the more sensitive it is to progesterone. If there is too much SGK1 production, the lining of the uterus essentially starts to slough off before it is fully ready to receive a fertilized egg. If there is too little SGK1 production, the uterus does not stabilize after the embryo is implanted and there may be miscarriage.

Why Do SGK1 Levels Fluctuate?

The genes that code the production of SGK1 are affected by vitamin A levels (too much vitamin A could result in deformity in the baby), vitamin D levels, dehydration, and high production of stress hormones.  Activation of the cancer watchdog gene p53 also activates production of SGK1. SGK1 seems to prevent pregnancy when the mother is not yet ready to carry a pregnancy to term.

SGK1 is not only active in the uterus. Scientists have investigated the role of this enzyme in the kidneys, relating it to high blood pressure. They have also investigated the role of SGK1 in the formation of bone and the role of SGK1 in diabetes. Only in October 2011, however, have scientists reported a possible role for SGK1 in female reproduction.
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  • Salker MS, Christian M, Steel JH, Nautiyal J, Lavery S, Trew G, Webster Z, Al-Sabbagh M, Puchchakayala G, Föller M, Landles C, Sharkey AM, Quenby S, Aplin JD, Regan L, Lang F, Brosens JJ. Deregulation of the serum- and glucocorticoid-inducible kinase SGK1 in the endometrium causes reproductive failure. Nat Med. 2011 Oct 16. doi: 10.1038/nm.2498. [Epub ahead of print]
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