Teratogenic+Effects+of+THC+and+Minoxidil

=By: Stacee Craig, Bridget Scherbarth, Erin Krause, and Kolbie Brichacek=

**Human Development**

 * Germinal Period**

Human development starting at conception through live birth is divided into three stages: the germinal period, the embryonic period, and the fetal period. The germinal period begins when an egg is fertilized by a sperm and ends about two weeks later with pregnancy established. During ovulation a mature egg travels from the ovary down the fallopian tube. While the egg is traveling down the fallopian tube, the sperm is traveling up the fallopian tube, and when they meet fertilization takes place.

Twenty-four to 36 hours after fertilization the first division occurs to produce two cells. Division continues leading to the formation of a morula and blastocyst. While division is continuing the cells are moving down the fallopian tube and will enter the womb where the blastocyst embeds itself into the uterine wall. Embedding in the uterine wall usually occurs by day five or six after fertilization. In the next five to seven days the placenta and circulation systems necessary for nutrients and gas exchange are developed. After these two weeks pregnancy is considered to be official and hormones are secreted to prevent menstruation. This ensures that the uterine lining is not shed and the mother’s immune system doesn't attack the developing fetus (Slater & Lewis, 2007).


 * Embryonic Period**

The embryonic period begins at the end of week two and ends just before the ninth week. During this period organogenesis occurs, or the formation of all the organs. At the end of this period the embryo will clearly have the physical appearance of a human. All organs originate as a single cell; differentiation and specification allow for specific organs to form. The environment of surrounding cells and signals play a significant role in specification. The brain begins development at 18 days after fertilization. By the end of week three the heart is two-chambered, is beating, and has established blood flow. Embryo waste is able to be removed and nutrients can be acquired. The sense of touch is the first sense to arise in a fetus and usually appears during week eight or nine. Since all of the embryo’s organs are developing during this period it is considered to be the most important (Slater & Lewis, 2007).




 * Fetal Period**

The fetal period begins at the ninth week and ends at birth. During this period development and differentiation continue that began during the embryonic period. Basic structures such as the two-chambered heart are even more distinguished and grow into their final forms such as a four-chambered heart. Rapid growth is also very noticeable during this time especially from 8 weeks when the fetus is only about one inch in size to 16 weeks when the fetus is usually about five to six inches. Motor, sensory, and learning behavior all emerge during this time as well. A fetus can respond to sound by weeks 22 to 24. At 26 weeks following fertilization a fetus has developed the sense of vision. Also at 26 weeks the sense of pain is developed along with neural pathways for pain (Slater & Lewis, 2007).


 * Other Development Information**

There appears to be three guidelines development tends to follow. The first guideline is that development is going to occur in the direction from head to foot, also referred to as cephalocaudal. The second is that basic structures will develop first then the more specialized structures. Lastly, development is going to occur in the order of importance, such as the brain and heart forming before toes (Slater & Lewis, 2007).



= **Minoxidil** =

Introduction Minoxidil is a drug that was originally used for the treatment of hypertension. Patients taking Minoxidil were found to have hypertrichosis, or hair regrowth. This discovery led to the development of a topical Minoxidil formula used to treat balding in both males and females (Messenger, A.G, and Rundegren, J., 2004). The use of Minoxidil in pregnant women has been shown to cause hypertrichosis in the infants. One case study showed that a woman maintained on a 10 mg regimen of Minoxidil daily during pregnancy gave birth to a baby with pronounced hypertrichosis of the back and extremities. Once the baby was born the hypertrichosis was noticeably reduced by two months of age (Kaler, S.G, Patrinos, M.E., Lambert, G.H., Myers, T.F., Karlman, R, and Anderson, C.L., 1987). It has been found that it is minoxidil sulfate which is responsible for the relaxation of vascular smooth muscle and cell grwoth. There have been studies done both in vivo and in vitro that show minoxidil becomes minoxidil sulfate when it is cataylzed by sulfotransferase (Buhl, A.E, Waldon, D.J., Baker, C.A., and Johnson, G.A., 1990).

Affects of Minoxidil on Development Minoxidil works to treat hypertension by opening up potassium channels. This promotes vascular smooth muscle relaxation and also cell growth. Medications that can affect potassium channels have the potential to also regulate cell growth and proliferation. This is why scientists believe Minoxidil can have adverse effects on a developing fetus. Minoxidil was first tested on pregnant rabbits and rats. These animals were very tolerant to the drug in small amounts. When the dosage was increased, more adverse developmental defects were seen such as, skeletal abnormalities and a higher rate of death of the offspring. In one case study, the pregnant mother was taking minoxidil along with three other hypertension drugs during pregnancy. Her infant was born with, according to Smorlesi, "hypertrichosis of the back and extremities, deformed facial features, cryptorchidism, clinodactilysm, and omphalocele," (Smorlesi, C., Caldarella, A., Caramelli, L., De Lollo, S., Moroni, F., 2003). Other developmental defects seen in infants born to mothers taking minoxidil include "brain defects, heart defects, deterioration of the lower body, aplasia of the lower spine, extra digits, and low set ears," (Symptoms, 2012). In a study done by the Florence Teratology Information Service, a 28 year old female had been using minoxidil while pregnant. She had a routine mid-trimester exam that revealed that the developing baby had some brain and heart malformation. The pregnancy was terminated and an autopsy was performed. The fetus had underdeveloped and hemorrhaged regions of the brain. The heart was enlarged and malformed. The blood vessels in the fetus were abnormal as well. The 28 year old female had a baby born, completely normal, two years later. She was not taking minoxidil during her second pregnancy (Smorlesi, 2003).



The best treatment option is to avoid using Minoxidil while pregnant. If a woman is taking Minoxidil while pregnant and notices anything strange during ultrasounds or other checkups, it is best to stop using Minoxidil right away. However, if any defects are present at this time they will still be there at birth, but at least the baby will not acquire anymore defects.
 * Treatments Options**

The studies done on the effects of Minoxidil on fetal development are somewhat inconclusive because most women taking Minoxidil were also taking other hypertension medications at the time of pregnancy. However, the reduction of hypertrichosis as the infant ages has been characteristic of many patients. More research will need to take place to determine the exact effects of the drug Minoxidil, but the evidence seems to suggest a strong correlation between the use of the drug while pregnant and hypertrichosis, as well as other malformations of the developing fetus.
 * Conclusion**

Buhl, A.E., Waldon, D.J., Baker C.A., and Johnson, G.A. (1990). Minoxidil sulfate is the active metabolite that stimulates hair follicles. //Society for Investigative Dermatology, Inc., 95// (5), 553-557. Kaler, S.G., Patrinos, M.E., Lambert, G.H., Myers, T.F., Karlman, R., and Anderson, C.L. (1987, March 3). Hypertrichosis and congenital anomalies associated with maternal use of Minoxidil. //Pediatrics, 79, 434-436.//
 * References**

Messenger, A.G, and Rundegren, J. (2004). Minoxidil: mechanisms of action on hair growth. //British Journal of Dermatology, 150, 186-194.//

Smorlesi, Carlo. Caldarella, Adele. Caramelli, Laura. De Lollo, Simonetta. Moroni, Flavio. (2003). //Topically Applied Monoxidil May Cause Fetal Malformation: A Case Report// : Wiley-Lis Inc. Retrieved from []

Symptoms of Minoxidil (topical)—Teratogenic Agent. (2012) .//rightdiagnosis.com//. Retrieved from [|http://www.rightdiagnosis.com/m/minoxidil_topical_teratogenic_agent/symptoms.htm#symptom_list]

(2011). //Werewolfboy syndrome//. (2011). [Web Photo]. Retrieved from http://www.google.com/imgres?q=hypertrichosis infant&hl=en&gbv=2&biw=1002&bih=553&tbm=isch&tbnid=aR5j9dGFixZReM:&imgrefurl=http://www.topyaps.com/?s=scientists&docid=HvU-ybePXwbJtM&imgurl=http://www.topyaps.com/wp-content/uploads/2011/05/werewolfboy-syndrome.jpg&w=450&h=308&ei=qieeT4wxjM70BP3t0OgO


 * Introduction Tetrahydrocannabino (THC)**

Tetrahydrocannabino (THC) is the psychoactive ingredient in marijuana which is either inhaled or ingested. Marijuana contains about 150 other compounds. The use of marijuana causes euphoria, slowed thinking and reaction time, altered perception and increase appetite to name a few types of effects (Djulus, Moretti, and Koran, 2005). THC causes the rapid release and uptake of the neurotransmitter norepinephrine. THC also increases thoughts and sensations (NIDA, 2006). After ingestion or inhalation, THC it is absorbed and distributed to the brain and fat tissue.




 * Affects of THC on Development**

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In 1982, Perez-Reyes and Wall found that .8% of maternal intake of marijuana per kilogram would be ingested by the infant through breast feeding. A study done by Astley and Little in 1990 provided support for the idea breast feeding by a marijuana smoking mother could cause her infant to have decreased motor development. Mothers who partake in smoking or ingesting marijuana frequently can have a build up of THC which can be passed to the baby though breastfeeding and negatively affect the brain development (Djulus, Moretti, and Koran, 2005).=====

According to Fried, Watkinson, and Willan, who conducted a study over the relationship between marijuana use during pregnancy and birth weight and length of gestation, marijuana had significant effect on gestation period, reducing it by 0.8 weeks. Five hundred and eighty-three women participated in the study and out of them 84 women used marijuana variously throughout their pregnancy. There was no reduction in birth weight noted in this study (Fried, Watkinson & Willan, 1984).

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Fertility treatments can be negatively affected by the use of marijuana. According to Klonoff-Cohen, long term use of marijuana decreases the amount of eggs which can be harvested from the woman. In addition, use by both partners can result in a decreased number of embryos which can be implanted. If the woman becomes pregnant, marijuana use can cause the fetus to have a low birth weight, which negatively affects the later development (//Fertility//, 2006).=====


 * Treatment Options**

The best option for treatment is pervention. Therefore, adults using marijuana should get drug treatment to stop their addiction in order to prevent the negative affects on children and fetuses

Since marjiuana, which contains THC, is an illicit drug, information is slim and more studies will need to be performed for the exact effect on devleopment.
 * Conclusion**

References

Djulus, Josephine, Moretti, Myla, and Koren, Gideon. (2005). //Marijuana Use and Breastfeeding.// Retrieved from []

//Fertility Can be Affected by the Use of Marijuana.// (2006). Retrieved from []

Fried, P., Watkinson, B., & Willan, A. (1984). Marijuana use during pregnancy and decreased length of gestation. //American Journal of Obstetrics and Gynecology//, //150//(1), 23-27.

ProCon.org. (2008, June, 16). //What is THC (Delta-9 Tetrahydrocannabinol)?// Retrieved from []

Slater, A., & Lewis, M. (2007). //Introduction to infant development//. (2 ed., pp. 41-62). Oxford, NY: Oxford University Press. Retrieved from []

//The science of marijuana: How thc affects the brain//. (2011). Retrieved from http://headsup.scholastic.com/articles/the-science-of-marijuana