IMPORTANCE OF VITAMIN D IN PREGNANCY, HYPERTENSION AND DIABETES

Vitamin D is a sun shine, fat soluble essential vitamin and steroid hormone which is synthesize in our skin after exposure to sunlight. There are mainly three sources through which we can get vitamin D,
1. By getting enough sunlight
2. Through vitamin D rich food such as egg yolk, fortified dairy products, fortified orange juice and cereals and fatty fish (salmon).
3. Through supplements as cholecalciferol (Vitamin D3) or as ergocalciferol (VitaminD2).
The active form of vitamin D is calcitriol or 1,25- dihydroxy vitamin D3.

IMPORTANCE OF VITAMIN D FOR HEALTH
As we all know about the importance of Vitamin D for bone health in calcification and in balancing calcium and phosphorus homeostasis but it has also significant role in many other functions of body such as in immune system, in musculoskeletal function, in mood regulations, diabetes, hypertension and in reproductive health including pregnancy outcomes, fertility and lactation. Recently, the role of vitamin D in reproductive health has been explored with reference to infertility and ART (assisted reproductive treatment technologies). Let’s discuss it,

ROLE OF VITAMIN D IN REPRODUCTIVE PHYSIOLOGY
Vitamin D has significant role in reproductive physiology of both male and female. In male, it is significant in steroidogenesis, spermatogenesis and in acrosome functions. The presence of vitamin D receptors (VDR) in ovarian granulosa and theca cells along with the key enzymes required for vitamin D synthesis and metabolism are detected locally within the ovary which clearly indicates that vitamin D may play a crucial role in regulation of different ovarian functions like follicular development, luteinization and in improving the quality of egg. To better understand, how vitamin D directly influence ovarian function, we will first try to understand the process of folliculogenesis as follow,

FOLLICULOGENESIS
Folliculogenesis is the process of the follicles growth, differentiation and maturation in different stages as follows,
• PRIMORDIAL FOLLICLES
Dormant follicles pool or immature follicles present at the time of birth in the ovaries or it can be define as oocyte (eggs) which is surrounded by granulosa cells.
• PRIMARY FOLLICLES
Primordial follicles grows into  primary follicles in which granulosa cells become cuboidal without the influence of gonadotrophins FSH (follicles stimulating  hormone) and LH (Luteinizing hormone).
• SECONDARY FOLLICLES
It can be define as pre antral stage in which granulosa cells continues to divide and formation of theca cells take place which releases androgens. At this point, FSH with the help of aromatase enzyme activate granulosa cells for conversion of androgen into estrogen.
• ANTRAL FOLLICLES
It is a tertiary stage in which a cavity filled with fluid is formed and continues to expand to mature the follicles under FSH and LH influence.
• MATURE FOLLICLES
It is also known as graafian or mature follicles which is ready to release fertilizable egg. It is pre ovulatory stage.
• OVULATION
Under the LH surge, fertilizable oocyte or egg releases into fallopian tube due to rupture of one dominant graafian follicle.
• CORPUS LUTEUM
Ruptured follicles transformed into corpus luteum which is a temporary endocrine gland and produces hormone particularly progesterone to maintain early pregnancy by preparing uterine bed for implantation.
• MENSTRUATION
If fertilization do not occurs corpus luteum degrades or degenerate into corpus albicans (function less) with the decline of hormones and there will be onset of menstruation.
Now, I will explore how vitamin D support different stages of folliculogenesis as follow,
• During early stages of follicles growth and development (largely preantral and early antral stages) granulosa cells produces AMH (anti mullarian hormone) a marker of ovarian reserves which indicate the presence of healthy eggs in the ovary. With the low serum level of vitamin D at primordial stage of folliculogenesis (a process of follicles recruitment and activation) AMH level will be declined and there will be premature depletion of dormant follicles pool. Therefore, we can say that with the deficiency of vitamin D, activation and recruitment of follicles are highly affected as indicated by low AMH level. Many studies are supporting the positive link between serum vitamin D level and AMH.
• At primary and secondary follicular stages vitamin D presence increases FSH receptors expression in granulosa cells which enhance the effect of FSH on follicles and with the stimulation of aromatase enzyme support the conversion of androgen into estrogen.
• At antral stage of folliculogenesis, vitamin D regulates androgen  production via adjusting theca cells function and support blood vessels formation for nutrients supply to growing follicles. At this stage, low vitamin D level may lead to PCOS ( poly cystic ovary) due to excess androgen production with decrease insulin sensitivity or increase insulin resistance due to excess male hormone which may arrest folliculogenesis and subsequently an ovulation can be observed in PCOS women.
• At pre ovulatory stage, vitamin D is involved in LH receptors expression for follicle maturation and may provide help against irregular ovulation during ovulation.
• At luteal stage, vitamin D support implantation and early pregnancy maintenance by producing progesterone which assist against miscarriages or early pregnancy loss.
In short, we can say that vitamin D is helpful against oxidative stress and inflammation. It lowers androgen levels, modulates immune system, improves insulin sensitivity and reduces insulin resistance with positive pregnancy outcomes. We can say, vitamin D deficiency is associated with the decline of AMH level and ovarian reserves. It improves ovarian follicle survival and growth, support implantation by enhancing endometrial receptivity due to in testify expression of genes responsible for implantation.

VITAMIN D AND IVF (IN VITRO FERTILIZATION)
In vitro fertilization (IVF) is one the procedure of assisted reproductive technologies or treatment (ART), during which adequate level of vitamin D is associated with successful pregnancy outcomes with live births. Research suggests that without vitamin D deficiency, there will be high quality embryo and chances to get pregnant is high.

ADVERSE PREGNANCY OUTCOMES DUE TO VITAMIN D DEFICIENCY
Vitamin D deficiency during pregnancy may results into,
1. Preterm birth
2. Preeclampsia (hypertension during pregnancy)
3.  Bacterial vaginosis
4. Neonatal death or mortality
5. Asthma in infants
6. Gestational diabetes (diabetes during pregnancy)

VITAMIN D AND PRECLAMPSIA
Vitamin D deficiency may result into preeclampsia during pregnancy and health care provider should take it into consideration for those women who are at risk. According to some studies findings, vitamin D deficiency increases the risk of preeclampsia while supplementation with vitamin D has proven to be helpful against preeclampsia.

VITAMIN D AND HYPERTENSION
Many observational studies suggest that insufficient vitamin D level may influence the blood pressure with the increase risk of hypertension and cardiovascular diseases. However, vitamin D supplements role in controlling hypertension is inconsistent. Some meta-analysis findings have not find any benefits of vitamin D supplementation in controlling or regulating high blood pressure while in some studies,
• Vitamin D supplementation is effective against the hypertension in older and obese people .
• Vitamin D3 along with calcium is found to be effective in improving blood pressure in type 2 diabetic patients and in elderly women.
• Vitamin D supplementation have shown reduction in diastolic blood pressure in cardiometabolic disorders patients.
We can say that relation between vitamin D and hypertension is complex and not fully clear but Vitamin D supplementation role  in preventing hypertension is required further research.

POSSIBLE MECHANISM OF ACTION
Vitamin D regulates renin angiotensin system which is link with blood pressure, promote vasodilation via nitric oxide production, maintain calcium homeostasis and reduces oxidative stress and inflammation which is also very important risk factor of preeclampsia and hypertension.

VITAMIN D AND DIABETES
Pancreas have vitamin D receptors due to which its deficiency may impaired insulin synthesis and secretion. Low vitamin D level has also been linked with oxidative stress and insulin resistance. Some studies findings support the role of vitamin D supplements in diabetic patients via better glycemic control due to reduction in inflammation and improvement of immune system (type 1 diabetes).  Some studies findings suggest that it may reduce the risk of developing diabetes in pre-diabetic patients. It enhances insulin secretion and improves insulin action by reducing insulin resistance. However, some studies findings don’t support the potential benefits of vitamin D supplements in diabetes.

PRECAUTIONS WHILE TAKING VITAMIN D
Vitamin D in supplement form may cause nausea and vomiting if taken on empty stomach, It should be taken with fatty meal for maximum absorption along with calcium, magnesium or vitamin K2 rich diet. At night, vitamin D supplements intake should be avoided because it may disturb the sleep cycle. Excessive intake may result into kidney stones, weaken bones and muscles and loss of appetite.

CONCLUSION
In the light of aforementioned discussions, importance of Vitamin D in reproduction, bones, diabetes and cardiovascular diseases is unbelievable. Vitamin D deficiency in infertility issues should be taken into consideration. Older adults are generally Vitamin D deficient which is associated with the risk of diabetes and hypertension. However, diet-based vitamin D sources along with sun exposure should be preferred over vitamin D supplements.