Fertility Switch: a Gene Responsible for Miscarriage and Infertility

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.

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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.

How Managing SGK1 May Give Women Greater Control Over Fertility

Hormonal management of fertility is a complicated process. Researchers hope that understanding the link between production of the SGK1 enzyme may lead to methods that ensure that the uterus is ready to receive the fertilized egg—or not, if the objective is contraception. There is also hope that understanding how to regulate the production of SGK1 may lead to better treatments for ovarian cancer, since the enzyme tends to "immortalize" ovarian cancer cells.

Any enzyme therapies for women who want to have babies, however, are at least 10 years off. In the meantime, there are important implications of research for women who want to conceive:

• The gene that codes for SGK1 is activated by hormones produced by stress. Although it's easier said than done, women who have a history of miscarriage may enhance their chances of carrying a pregnancy to term by avoiding stress, especially when trying to conceive and during the first month of pregnancy. Meditation, yoga, and acupuncture have all helped women overcome stress so that they could maintain pregnancy.
• The gene that codes for SGK1 is also activated by vitamin A and similar chemicals. Although only about 10% of women exposed to high levels of vitamin A during early pregnancy bear children with genetic deformities, birth defects caused by vitamin A toxicity tend to be severe. Excessive levels of vitamin interfere with the formation of the forebrain/cerebral cortex and facial features. SGK1 sometimes terminates these pregnancies. To avoid the problem, never take more than 5000 IU of vitamin A day, don't consume more than 1 teaspoon (5 ml) of cod liver oil per day, and don't use Accutane or Retin-A in pill form for acne if you want to become pregnant.

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• Women who have diabetes during pregnancy tend to have very large babies. With appropriate medical support, even babies weighing as much as 9 kilos (19 pounds) at birth can be born healthy, but the process of giving birth causes enormous strain on the mother and before modern obstetric procedures were available many infants suffocated during the birth process. SGK1 is essential for the mother's body to absorb the excess sugar that is generated during gestational diabetes—and it is activated by vitamin D. Taking up to 1000 IU of vitamin D per day during early pregnancy may offset risks of gestational diabetes. It is still necessary to get prenatal care even if you are getting vitamin D.
• Allergy-prone mothers tend to have allergy-prone babies. SGK1 also plays a role in causing cells to swell fluid that bursts tiny packets of histamine, the chemical that causes the symptoms of allergies. In this process, SGK1 is activated by stress. Avoiding stress during pregnancy helps mothers avoid allergies, and also reduces the likelihood of diaper rash, eczema, and allergy-induced breathing problems in the infant when he or she is born.

An expert on fluid physiology and a practicing physician for 65 years named Demetrio Sodi-Pallares had one more suggestion for women who trying to conceive that can be explained in terms of SGK1 but that does not require any special scientific background to carry out. Women who are infertile sometimes respond to a low-sodium diet. Avoiding packaged foods and eating about 9 servings of fruit and vegetables per day offsets the "drying" effects of SGK1 and sometimes helps women get pregnant. It's a very easy intervention that can only benefit both mother and child.

And if eating fruit and vegetables makes the mother-to-be queasy, it's time for a pregnancy test. Morning sickness is a sign that conception was successful.