Physiological Changes During Pregnancy

Pregnancy is associated with many physiological changes in a woman’s body and these changes promotes healthy development of the fetus. Pregnancy related physiological changes initiate after conception and affect every organ systems. Pregnant women are more likely to experience symptoms of nausea and vomiting, which are adaptive mechanisms during pregnancy, to prevent women from consuming teratogenic substances. Such etiology of pregnancy is also linked to many pregnancy associated hormones such as human chorionic gonadotropin (hCG) hormone and oestrogen (Soma-Pillay et al. 2016). The main purpose of this report is to discuss the role of hormones during pregnancy and provide a  detailed insight into the function of different hormones during different stages of pregnancy.

The endocrinology of human pregnancy is an important factor that helps to maintain a healthy pregnancy. The endocrine changes occur because of physiological alterations in the feto-placental unit (FPU). The FPU is the boundary site between fetus and mother and it is the site where hormonal production and secretion takes places. Hormonal signals originating from FPU during pregnancy are linked to endocrine and metabolic changes in pregnant women. Both neuronal and hormonal factors maintain the pregnancy and its associated changes. Proper timing between neuro-endocrine events facilitates fetal growth. Progesterone, estrogen and hCG are some key hormones involved during pregnancy and the function and role of each hormone in pregnancy physiology is explained in detail in the next section (Bazer 2012)..

Figure 1: FPU, the boundary between fetus and mother and a major site for protein and steroid hormone production and secretion. Source: (Bazer 2012). 

Progesterone:

Steroid hormones like progesterone is produced extensively during pregnancy. For instance, the synthesis and secretion of progesterone from corpus luteum initiates from the fourth week of gestation until the placenta grows up by eighth week to actively synthesize the hormone. About 250mg/day of progesterone is produced from placenta during pregnancy. Placenta synthesizes progesterone from cholesterol by forming pregnenolone followed by its hydroxylation to produce the hormone (Kumar and Magon, 2012). Hence, placenta is the unit where progesterone is produced and secreted.

Progesterone plays a crucial role in each stage of pregnancy. It plays a role in the process of reproduction by inducing changes in the lining of uterus and promoting successful implantation of the embryo. During early pregnancy, it induce immune response in the mother’s body to prevent rejection of the embryo. In the first trimester, it is mainly involved in maintaining health and development of fetus by thickening the uterine lining and maintaining optimal function of the placenta. It also prevents contraction of the uterus allowing the baby to expand in the womb (Dante,Vaccaro and Facchinetti 2013). In the second and third trimester of pregnancy, progesterone also reduces the risk of preterm birth. The secretion of progesterone increases in the second semester and by the last trimester, the volume of progesterone increases from 340 to 675 nmol/L (Edelstam et al 2007).  Hence, it can be concluded progesterone hormones supports the endometrium to provide conducive environment for the survival of the fetus. The binding of progestin to the progesterone receptor help in maintaining pregnancy (Soma-Pillay et al. 2016).  

Endocrinology of Human Pregnancy

 

Figure 2: Production of progesterone in the placenta Source: (Openi.nlm.nih.gov. 2018)

Estrogen:

Another steroid hormone that greatly regulates physiological mechanism during pregnancy includes the estrogen hormone. Estrone, estradiod and estriol are three major forms of estrogen hormones and the synthesis of the hormone starts from the theca interna cells. These cells convert cholesterol into androstenedione, which is then converted into estradiol in the granulose cells (Kumar and Magon, 2012). Hence, granulose and theca cells are responsible for the synthesis estrogen hormones. During the first stage of pregnancy, estrogen maintains a healthy pregnancy by increasing the number of blood vessels going to the uterus. In this way, blood flow is increased and enough nutrients are available for the development of the fetus. It also acts to increase the size of uterus by thickening the uterine wall and preparing it for implantation. The production of estrogen starts in the first trimester and continues until the last stage when the circulation of the hormones increases considerably.  During the second trimester, increase in levels of estrogen is also associated with building’s pregnant women’s readiness for lactation through milk duct development. The level of estrogen reaches it peak in the third trimester. The increase in level in the fisrt trimester leads to symptoms of nausea and in the second trimester, it leads to enlargement of breast (Sanchez et al. 2015).

Just like progesterone, estrogen also improves immune functions of women during the immune-compromised state of pregnancy. The evidence by Khan and Ansar Ahmed (2016) gives detailed insight into the role of estrogen on the cells of the immune system. It regulates the number and function of neutrophils. However, such kind of response of estrogen on the immune system is dependent on level of estrogen produced and the local environment surrounding the hormone.

Figure 3: Role of theca and granulose cells in the production of estrogen hormones. Source: (Doshi and Agarwal 2013)

hCG:

Apart from steroid hormones, there are also protein hormones like hCG that is produced in large amount during early stage of pregnancy. The most vital role of hCG in pregnancy is that it regulates the function of the corpus luteum which in turn facilitates the production of estrogen and progesterone. The hCG hormone is produced by the trophoblast layer of the blastocyst during the early phase of pregnancy and its level of secretion decreases during the second and third stage of pregnancy. About 120 to 130 IU/ml of hCG is produced during pregnancy and its amount decrease to about 20-30 IU/ ml by the 16^th week of pregnancy (Korevaar et al. 2015). During the first trimester of pregnancy, the main role of hCG is to keep the corpus luteum alive. This occurs by the interaction of the hormone with the LHCG receptor of the ovary. This also facilitates secreation of progesterone during the first trimester (Evans et al. 2015). In contrats to first trimester, the level of estrogen decreases in the second and third trimester.  Corpus luteum is the organ which establishes and maintains pregnancy in women. Corpus luteum makes pregnancy viable. As the role and development of steroid hormone at different stages of pregnancy have been discussed, the given below graph provides a better insight how level of each of three hormones increases and decreases during different stages of pregnancy.

Progesterone Hormone During Pregnancy

 

Figure 4: Relative concentration of hormones during different weeks of pregnancy. Source: (Din 2016).  

In addition to maintaining the function of corpus luteum, the hCG hormones are also found to stimulate corticosteroid production. This is also an important function in pregnancy physiology as it eliminates any immune response towards the fetus by not regarding it as a foreign body. There are many evidences that recognizes the role of hCG in pregnancy immune tolerance. Schumacher et al. 2013) also explained that fetal survival within the uterus is possible because of many hormonal changes and their role in regulating maternal immune response towards the foreign fetal antigens. Hence, it can be said that effective interaction between hormonal and immunological factors results in fetal tolerance during pregnancy.

After the discussion on the function of hCG, estrogen and progesterone hormones, their role in maintaining successful pregnancy outcome is even more clear. The hCG reaches its maximum level during 9^th to 12^th week and declines thereafter until birth. After the 12^th week (second trimester), it mainly involved in supporting angiogenesis and ensuring nourishment of the fetus. It manages to do so by attracting regulatory T cells (Tregs) to trophoblast. The more is the expansion of the Treg cells, the higher is the establishment of pregnancy. The transfer of Treg cells minimizes chances of fetal rejection. It creates a tolerant microenvironment at the FPU unit (Muzzio, Zygmunt and Jensen 2014). Hence, hCG acts as the chemo-attractant of tregs that triggers immune tolerance of the fetus during pregnancy and other steroid hormones act as the source that confers immune suppressive capacity to B lymphocytes. By the third trimester, the hormone is involved in promoting relaxation of the uterine contraction and initiating onset of labour (Edelstam et al. 2007).

hPL:

Another protein hormone involved in regulating changes during pregnancy includes the Human placental lactogen (hPL) hormone. This exclusive pregnancy hormone is also produced in the placenta. In the first trimester, it maintains health of the fetus by maintaining energy supply of the fetus. It is secreted by synctiotrophoblast at the time when the production of hCG decreases. One of the important and vital attributes of this hormone is its anti-insulin properties. Insulin resistance is the decrease in target tissues ability to respond to normal concentration of insulin. This is also an adaptive changes seen in pregnant women where mother utilizes more fats and more carbohydrates is reserved for fetus. This condition ensures that the growing fetus gets ample amount of carbohydrate as a form of energy. However, increased production of hPL in the third trimester of pregnancy results in decline of insulin sensitivity by 50%. The increase in estrogen and progesterone level also decreases insulin sensitivity (Sonagra et al. 2014). Hence, increases insulin resistance should be controlled in patient as it results in premature labor as well as fetal complications. Taking balanced diet and engaging in mild exercise can prevent insulin related complications in patients. 

Estrogen Hormone During Pregnancy

The above discussion related to the role of hPL indicates the endocrinal mechanism involves in insulin resistance during pregnancy. The discussion of different maternal adaptations and hormonal changes during pregnancy also signifies how effective production and secretion of hormones regulates the health of fetus. However, abnormal or undesired concentration of hormones may also cause complications in pregnancy. For example, the concentration of thyroid hormone also increases during 6-12 week of pregnancy. Abnormal concentration may disrupt the function of thyroid hormone thus increasing the likelihood of thyroid disease during pregnancy (Costantine 2014). Hence, it is necessary to monitor endocrinological parameters during early gestation period. This may help to detect any complications in the developing fetus and chances of abnormal pregnancies.

Conclusion:

The report gave an insight into the physiological changes seen in a pregnant woman due to hormonal changes. Several adaptations take place during pregnancy. Some of the adaptations are related to the production and secretion of hormones to support the developing fetus. The discussion gave an insight into the role of steroid and protein hormones in the development and nourishment of fetus. The increase and decline in production of each of these hormones at different stages signify their specific role in maintaining the optimal health of fetus. Apart from the role of different hormones in supporting the fetus, hormones like estrogen and hCL has also been found to enhance immune response in pregnant women’s body. For instance, the role of hCL in incorporating immune tolerance of pregnant women’s body to the developing fetus is also one of the remarkable features that depicts its role in immune system. Hence, changes in concentration of hormones serve different adaptive purpose for the healthy development of fetus However, abnormal concentration increases chances of many diseases too. Therefore, it is necessary to monitor such changes in pregnant women to ensure they have a normal pregnancy. 

References

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Costantine, M., 2014. Physiologic and pharmacokinetic changes in pregnancy. Frontiers in pharmacology, 5, p.65.

Dante, G., Vaccaro, V. and Facchinetti, F., 2013. Use of progestagens during early pregnancy. Facts, views & vision in ObGyn, 5(1), p.66.

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Doshi, S.B. and Agarwal, A., 2013. The role of oxidative stress in menopause. Journal of mid-life health, 4(3), p.140.

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Evans, J., Salamonsen, L.A., Menkhorst, E. and Dimitriadis, E., 2015. Dynamic changes in hyperglycosylated human chorionic gonadotrophin throughout the first trimester of pregnancy and its role in early placentation. Human Reproduction, 30(5), pp.1029-1038.

Khan, D. and Ansar Ahmed, S., 2016. The immune system is a natural target for estrogen action: opposing effects of estrogen in two prototypical autoimmune diseases. Frontiers in immunology, 6, p.635.

Korevaar, T.I., Steegers, E.A., de Rijke, Y.B., Schalekamp-Timmermans, S., Visser, W.E., Hofman, A., Jaddoe, V.W., Tiemeier, H., Visser, T.J., Medici, M. and Peeters, R.P., 2015. Reference ranges and determinants of total hCG levels during pregnancy: the Generation R Study. European journal of epidemiology, 30(9), pp.1057-1066.

Kumar, P. and Magon, N., 2012. Hormones in pregnancy. Nigerian medical journal: journal of the Nigeria Medical Association, 53(4), p.179.

Muzzio, D., Zygmunt, M. and Jensen, F., 2014. The role of pregnancy-associated hormones in the development and function of regulatory B cells. Frontiers in endocrinology, 5, p.39.

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Schumacher, A., Heinze, K., Witte, J., Poloski, E., Linzke, N., Woidacki, K. and Zenclussen, A.C., 2013. Human chorionic gonadotropin as a central regulator of pregnancy immune tolerance. The Journal of Immunology, 190(6), pp.2650-2658.

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Sonagra, A.D., Biradar, S.M., Dattatreya, K. and DS, J.M., 2014. Normal pregnancy-a state of insulin resistance. Journal of clinical and diagnostic research: JCDR, 8(11), p.CC01.