Lecture 3 - Nutrition Status and Reproduction, Nutrition Prior to Pregnancy Flashcards
1
Q
Explain the reproductive systems for females?
A
- Born with immature ova (eggs). About 7 million ova but only about 300,000 at puberty
- Starting at puberty - ova mature about every 28 days (ovulation)
- Ova mature within follicles in the ovaries
- Decades of exposure (think when you have a girl she is carrying the potential for your grandkids too)
2
Q
Explain the reproductive systems of males
A
- Born with sperm-producing systems
- Start producing sperm at puberty - ongoing not cyclic
- More susceptible to shorter exposures (unlike females)
- Response to testosterone is 70-80 days
3
Q
What are endocrine organs associated with reproduction and what hormones do they release?
A
- Hypothalamus - releases gonadotropin releasing hormone (GnRH)
- Pituitary - releases follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
- Ovaries and placenta from adrenal glands, adipocytes - releases estrogen and progesterone (testosterone)
- Testes (adrenal glands) - releases testosterone
- happens in both males and females
4
Q
Explain the hypothalamus-anterior pituitary-gonadal axis for men
A
- Hypothalamus sends GnRH to the anterior pituitary which releases LH and FSH.
This stimulates the testes (ovaries in women) they then release testosterone (estrogen). - Release of testosterone causes a negative feedback to hypothalamus and the anterior pituitary
5
Q
Explain how hormone levels change during the menstrual cycle
A
- Days 1-7 (Follicular phase): FSH and LH stay level, growth of the follicle, estrogen increasing until day 12, progesterone stays level
- Day 12-14: LH increase triggering ovulation , FSH increase, estrogen drops, progesterone starts to increase
- Day 14-28 (Luteal phase): thickening of ednometrial lining lining, progesterone levels increase and estrogen levels stay the same, LH and FSH levels are lower
6
Q
What effect does obesity have on fertility?
A
- Associated with infertility or subfertility in both females and males
- Excess adipose tissue, particularly excess visceral adipose tissue, alters hormones involved in reproduction
- Result of overnutrition which is common in today’s society
7
Q
Explain how hormones impact the male reproductive system?
A
- GnRH levels fluctuate»_space;> LH and FSH release»_space;> Testosterone release from testes
- Testosterone and other androgens stimulate the maturation of sperm (70-80 days to mature)
- Mature sperm stored in the epididymis until released (released in semen which contains fluid and nutrients)
8
Q
Explain how undernutrition impacts fertility in males and females
A
- Females: hypothalamic amenorrhea (e.g. female athlete triad)
- Males: impaired sperm number, viability, and motility, decreased sexual drive
- Caused by negative energy balance, weight loss, low body fat, (can be from intense physical exercise)
- Nutritional status impacts the status of hormones thus causing the above impacts
- In women, body senses that organs are not capable of hosting an embryo so it is protecting the host
- Acute malnutrition has a larger impact than chronic malnutrition because we are able to adapt (growth can still be disrupted)
9
Q
Why was there a reduction in births during the Dutch Famine (44/45)
A
- Malnutrition due to rationing
- Men away to war
- High stress situations
- Other reasons, not solely due to nutrition
10
Q
What effects do micronutrients have on fertility? Give examples of micronutrients
A
- Antioxidants have role in protection of ovum/corpus luteum and sperm from reactive oxygen molecules
- Vitamin C, Vitamin E, beta-carotene, selenium
- Lower intake of antioxidants associated with infertility
- Zinc has a role in testosterone synthesis and sperm maturation
11
Q
How do BMI and waist circumference impact health risk?
A
- Underweight and overweight have increased health risk
- Obese 1 = high
- Obese 2 = very high
- Obese 3 = Extremely high
- Waist circumference of >102cm for males and >88cm for females (indicates central adiposity) can also indicate health risk
- You can have a healthy BMI but a large waist circumference that will lead you to health risk
12
Q
How can obesity specifically impact females and their fertility?
A
- Can cause menstrual irregularities due to:
1) Increased androgens (testosterone)
2) Increased leptin (made by adipose. Increased adipose = increased leptin. Triggers first menses in women) and estrogen
13
Q
Explain what PCOS is and what occurs with this syndrome
A
- Polycystic ovarian syndrome
- Related to obesity leading to infertility
- Hyperandrogenism (elevated testosterone)
- Impaired ovarian folliculogenesis (due to hyperinsulinemia) - insulin resistant
- Associated with android fat distribution
- Overall creates a hard layer around ovaries which disrupts the cycle within the ovary (not undergoing ovulation)
- Some researchers say it is the female manifestation of metabolic syndrome
14
Q
In PCOS what comes first, insulin resistance or hyperandrogenemia?
A
- Genetic programming, central obesity, and diet can lead to IR or Ovarian steroidogenesis (hyperandrogenemia) these then can lead to the other
- Ultimately culminates in PCOS which will cause dyslipidemia, cvd, diabetes risk, and higher bp
15
Q
How can obesity impact male fertility? How does this occur?
A
- Males: decreased sperm count and motility, increased risk of erectile dysfunction
- Decreased testosterone
- Leptin, estrogen
- Increased scrotal temperature (sperm need optimal temperature, otherwise proteins denature)
- J shaped curve for BMI and risks (underweight will also have these risks which is the same for women)
16
Q
What other nutritional factors are associated with infertility for males and females?
A
- Females:
- Vegetarian/vegan if not doing it properly
- Iron status (important in fertility cycle)
- Alcohol
-Males: - Vitamin D
- Alcohol
- Heavy metals, chemicals (occupational exposure rather than day to day (atypical exposure))
17
Q
What are the 3 critical periods of fetal development for organ and tissue development?
A
1) Hyperplasia (increased cell multiplication)
2) Hyperplasia and hypertrophy
3) Hypertrophy (Increased cell size)
- hyperplasia requires an environment that is optimal. If not there can be an insult or change that is irreversible
18
Q
What does critical period mean in fetal development?
A
Point of time when environment should be optimal. If it is not there can be no reversing changes
19
Q
When can major congenital anomalies occur vs functional defects and more minor anomalies?
A
- major congenital anomalies occur in highly sensitive periods of growth in the first 8 weeks of pregnancy
- Less sensitive periods begin later, dependent on what you are looking at
- CNS has the longest sensitive period lasting until 16 weeks
- During highly sensitive periods exposures/illness/nutrient deficiencies can have impacts that cannot be reversed
- If exposures occur in less sensitive periods it is possible that they may be reversed
20
Q
Why is nutritional status prior to pregnancy important?
A
- Some critical periods of fetal development occur before women know they are pregnant
- If nutrients unavailable during critical period, can not ‘catch-up’ later (effects not reversible)
- Teratogens (toxins) need period of time to clear circulation
21
Q
What are neural tube defects (NTDs) and when do they occur?
A
- Failure of closure of the neural tube during early development
- Week 3 and 4 (women wouldn’t know they are pregnant, as a result is the most common defect)
- Various presentations and degrees of severity
- Mechanisms are unclear but link to folic acid
22
Q
What are the two phases of female reproduction?
A
Follicular and luteal
23
Q
What occurs during the follicular phase?
A
- Day 1 to 14
- Low estrogen and progesterone»_space; release of GnRH»_space; release of FSH and LH
- Growth and maturation of follicles and ova
- Release of estrogen (and progesterone)
- Thickening of outer uterine wall (endometrium)
- Peak LH levels stimulate ovulation (day ~14)
24
Q
What occurs during the luteal phase?
A
- Day 15 to 28
- Follicle becomes corpus luteum»_space;> releases progesterone and some estrogen»_space;> further endometrium development»_space;> inhibit GnRH
- If no fertilization: corpus luteum shrinks»_space;> progesterone and estrogen levels decline
- If fertilization: corpus luteum size increases»_space;> continued release of progesterone and estrogen
25
Q
How is the Neural tube formed?
A
- start with a neural plate
- series of folds and involutions that form CNS
- results in the formation of neural crest and spinal cord
- all occurring within 4 weeks
26
Q
What is the prevalence of NTDs?
A
- NTDs most common congenital anomaly in US and Canada
- 1.0-1.6 per 1000 live births
- Many suspected to be miscarried
- long history of discovery
27
Q
What are the different types of NTDs?
A
- Anencephaly: incomplete brain formation, absence of forebrain and skull. The neural tube not closed at all
- Encephalay: protrusion of brain and membranes through skull (depends on length of exposure or what they are exposed to)
- Spina bifida: incomplete spinal cord formation (severity depends on formation and defect)
28
Q
What are the clinical symptoms of spina bifida?
A
- Lump formed that is made of nervous tissue, never normal
- Control of muscles distal to (below) defect affected (often lower limbs, bladder, large intestine)
- If defect is high in spinal cord, death may occur
- Surgery in utero to fix
29
Q
What is the link between folate and NTDs?
A
- women who give birth to babies with NTDs have lower serum folate and dietary intake of folate
- epidemiological studies show regions with higher dietary folate intake have lower rates of NTDs
- Women who take supplement containing folate before and during pregnancy have lower risk of having baby with NTDs
30
Q
What is folate and its forms?
A
- It is a B vitamin so is water soluble and is able to donate a methyl group (Glutamate/glutamine)
- Family of compounds:
- Folate: polyglutamate
- Folic acid: monoglutamate - more stable, what you would find in a supplement
- Bioactive form: tetrahydrofolate
31
Q
Explain metabolism of folate
A
- Folate in our circulation comes into cell with a carrier to become 5-MeTHF
- 5MeTHF can be used for methylation reaction or nucleotide synthesis
- Methylation pathway requires B12 and B6 and SAM (methyl donor) for conversion into homocysteine
- Methylation of DNA for gene regulation, protein for structure and function, and lipid for synthesis
- Other pathway is for formation of DNA and requires 5,10 Methylene THF reductase (known snp)
- Pathways are regulating each other
32
Q
How does folate decrease NTDs?
A
- Mechanism not completely understood
- Methylation is likely the connection between folate and NTDs
- Reduction in 5,10 Methylene THF will alter flux and reduce methylation pathway
33
Q
There are variations in MethyleneTHF Reductase gene. What are they and how do they impact NTDs?
A
- Variance gene is associated with increased plasma homocysteine and risk of NTD
- CC = normal MTHFR
- CT = heterozygous variant (est 40% population) and increases risk of NTDs (OR 1.1 to 1.3)
- TT = homozygous variant (est 10% population) and highest risk of NTDs (1.6 to 1.9)
34
Q
What two things influence folate metabolism and what can this result in?
A
- Environment and genetics can alter folate metabolism
- Causes a decrease in methylation of proteins, lipids or metabolites
- Altered protein function and gene expression
- Leads to NTDs
35
Q
How do DNA synthesis and methylation interact?
A
- increased DNA synthesis and decreased methylation (TT)
- Decreased DNA synthesis and increased methylation (CC)
- Middle = CT
36
Q
What are the folate equivalents?
A
- 1 Dietary Folate Equivalent (DFE):
= 1 ug food folate
= 0.6 ug synthetic folic acid (more bioavailable) with food
=0.5ug synthetic folic acid from supplement on empty stomach
37
Q
What are the folate requirements?
A
- RDA (adult females): 400ug/day
- RDA (pregnancy): 600ug/day
- UL (synthetic folic acid only): 1000 ug/day
38
Q
Should pregnant women supplement with folate?
A
- Health Canada recommends women who can become pregnant should take 400ug synthetic folic acid/day from multivitamin supplement
- Premise - based on data collected over a long period of time, it appears that women don’t (generally) meet folic acid recommendations
39
Q
Give examples of food sources of folate
A
- Naturally occurring folate:
- Vegetables: peas, beans, asparagus, dark leafy greens
- Fruits: oranges, orange juice, pineapple juice
- Fortified foods: Bread and grain products
-150 ug folic acid/100g flour - 200 ug folic acid/100g pasta
40
Q
Does folate fortification help reduce NTDs in Canada?
A
- Prevalence of open NTDs in Ontario:
- 1.13 per 1000 pregnancies before 1998 (prior to fortification)
- 0.52 per 1000 pregnancies in 2000 (reduced prevalence by half)
- Similar decreases in anencephaly and spinal bifida
- Folic acid in excess on high fat diet showed offspring are gaining more weight than those who did not have excess folic acid
41
Q
What are teratogens and give examples of them
A
- Substances that can produce or increase the incidence of an abnormality in embryonic or fetal development
- Drugs (including alcohol), chemicals, infections, radiation
- Vitamin A, lead, mercury
42
Q
Is Vitamin A toxicity a concern? Where does it result from?
A
- In developed countries vitamin A toxicity is a greater concern than deficiency
- In developing countries vitamin A deficiency is common
- Vitamin A is a teratogen in mega doses
- Toxic level not usually from food but a result of:
- Mega dose supplements
- Retinoid drugs (accutane)
43
Q
What can retinoid drugs do?
A
- Retinoid drugs such as isotretinoin (e.g. Accutane)
- Increased risk of spontaneous abortion and birth defects
- Craniofacial defects, cleft palate, cardiovascular and CNS abnormalities
- Neuropsychological impairment later in life
44
Q
What is the RDA and UL for Vitamin A?
A
RDA: 700 ug/d
UL: 3000 ug/d (pre-formed only)
45
Q
What should you do to avoid Vitamin A related defects?
A
- Avoid megadose supplements: increased rate of birth defects with 3,000 ug/d
- More than one form of birth control while taking retinoid drugs and stop use at least 6 months before pregnancy (store in fat so it stays in the body longer)
- Beta carotene is okay
46
Q
What is methyl mercury, where do we get it, and what can it do?
A
- Methyl mercury is a teratogen
- Main food source of methyl mercury is contaminated fish
- Diet high in mercury before and during pregnancy can cause CNS defects including cerebral atrophy, seizures, mental impairment, blindness
47
Q
Should women eat fish while pregnant?
A
- Fish is a good source of long chain omega-3 fatty acids that are important for fetal brain development
- Health Canada reports that most fish in Canada have very low mercury levels (exceptions are fresh or frozen tuna, shark, marlin, orange roughy, escolar, and canned albacore tuna)
- Large predatory fish have larger amounts of mercury because it accumulates over food chain (algae-small fish-big fish)
- Women who are planning to get pregnant or those who are currently pregnant are advised to have at least 150g of cooked, low mercury fish each week (2-3 servings of fish a week in CFG)
48
Q
Why should pregnant women not drink alcohol?
A
- Alcohol is a teratogen and it crosses the placenta and the fetal liver can not metabolize
- Most affected is CNS development (CNS is earliest and longest) as it is a critical period through-out pregnancy
- Heavy alcohol intake causes increased risk of miscarriage, stillbirth and infant mortality
49
Q
What is FASD? What is it caused by and what are the symptoms?
A
- Fetal alcohol spectrum disorder (mild to severe cases)
- Growth impairment, neurological abnormalities, facial characteristics
- Developmental delays, behavioural and learning disabilities (some of these don’t show until they are older)
- Alcohol consumption during pregnancy is thought to be the most common cause of impaired mental functioning
- Have a flat midface, short nose, indistinct philtrum, thin upper lip, short palpebral fissures
50
Q
How much alcohol should pregnant women consume?
A
- Unknown if there is a safe level and likely varies between individuals
- Alcohol should be completely avoided before and during pregnancy
