Reproductive Toxicology Flashcards by Eric Juneau

What are the 10 stages of the reproductive cycle?

Fertilization
Zygote transport
Implantation
Embryogenesis
Fetal development
Parturition
Lactation/Postnatal development
Growth and development
Sexual maturation
Gamete production and release

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The 10 reproductive phases are divided into 3 testing segments, what are they and which phases do they contian?

Segment 1: Fertility (begins at sexual maturation)
- Gamete production and release
- Fertilization
- Zygote transports
Segment 2: Embryotoxicity, teratogenicity (begins at implantation)
- Embryogenesis
- Fetal development
Segment 3: Pre-postnatal toxicity (begins at parturition)
- Lactation and postnatal development
- Growth and development

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What are the 3 pituitary hormones that act on gametes in women? Which cells do they act on? What do those cells release? Where do those hormones act?

LH - Theca cells
FSH - granulosa cell - Estradiol
Prolactin - Corpus Luteum - Progesterone
E2 and P4 act on: Vagina, Cervix, Uterus, Oviduct

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How do FSH and LH act in males? What cells do they act on, what do those cells release, and where do those hormones act?

LH - Leydig Cell - Testosterone
FSH - Sertoli Cell - Inhibin
Inhibin: -ve feedback
Testosterone: -ve feedback but also:
Spermatognesis
Accessory sex organs
Masculinization

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Testosterone is synthesized from what molecule?

Cholesterol

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What drugs/chemicals cause Leydig Cell Hyperplasia/Neoplasia?

Like everything

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What is a syncytium?

A multinucleated mass

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True/False? Due to the many stages of sperm development it is difficult for a toxin to damage a sperm

False

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True/False? Deficiency in a single vitamin is enough to cause spermatogenic arrest in humans

False, in animals though

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What are the functions of the epididymis?

Absorption
Secretion
Transport
Maturation
Storage

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What properties of sperm are analyzable?

Viscocity
Volume
Number
Concentration
Motility (velocity/motile density)
Morphology

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DNA is ___-fold more compacted in sperm than in somatic cells

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What are chromatin biomarkers for sperm quality?

Sperm decondensation
Breaks/Cross-links/Integrity of chromatin
Chromatin template function
Chromatin structure
Chromatin Epigenome

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What are the 4 standard measures of reproductive toxicology?

Fertility
Testicular histology
Testis weight
Gene expression

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What are the advantages of fertility as a reproductive procedure?

+ Integrates all reproductive functions

- Insensitive

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What are the advantages of testicular histology as a reproductive procedure?

+ Information on all target cells

- Subjective (not quantitative)

What are the advantages of testis weight as a reproductive procedure?

+ Rapid, quantitative

- Less sensitive than sperm count, affected by edema

What are the advantages of Gene expression as a reproductive procedure?

+ comprehension

- “overly” sensitive, hard to assess what matters

Is sperm count declilning?

yes

Does maternal smoking during pregnancy affect sperm count?

Yes

Is testicular cancer becoming more incident?

yes

Is hypospadia more prevalent?

Yes

What is testicular dysgenesis syndrome?

Te effect of environmental EDCs and Genetic defects causing disturbed Leydig/Sertoli cell function, leading to:
Decreased germ cell differentiation
Decreased androgens
Decreased insl3
These lead to several consequenses:
Decreased sperm quality
Carcinoma in situ
Hypospadias
Testicular maldescent

When are doses given for a Multigeneration REproduction study? when are assessments made?

Doses: All stages
Assessment: G/D and Sex mat

When are doses given for a Fertility and embryo development study? when are assessments made?

Doses: G/D, Sex mat., Gam prod/rel. Fert, Zyg trans, impl Assessment: Parturition

When are doses given for an Embryo-Fetal Development study? when are assessments made?

Doses: Impl, Embryogen, Fetal dev. Assessment: Parurition

When are doses given for an pre/post development study? when are assessments made?

Doses: Imp, embryogen, fet dev, Part, Lac/Posn dev Assessment: Sex mat

What structures does Cyclophosphamide act on? | What type of alkylating agent is it?

DNA RNA Protein Bifunctional Alk agent

What was the result of CPA treated rat sperm's cell length after six weeks?

They were shorter by almost 50%

What was the result of FISH in spermatozoa from CPA treated rats?

aneuploidy

What did the Comet assay of CPA treated rats reveal?

Increased % of abnormal sperm

What are the effects of paternal CPA exposure on early embryos?

Chromatin remodelling Pronuclear formation Zygotic genome activation Cell lineage determination

What happened to the embryos of gavaged/proestus mice?

Developmental stage was farther along | eg Day 2 of gestation, Day 8 of development

Histone acetylation is correlated with _____ of zygotic genome in early embryonic development

Activation

CPA exposed spermatozoa showed _____ histone acetylation

Increased

DNA methylation occurs at the _________ CH3 is added by _______ CH3 is removed by _______

5-position Cytosine SAM (S-adenylmethionine) DNMT (DNA methyltransferase)

5MeC fluorescence intesnsity was ____ in embryos sired by CPA-treated rats compared to saline-treated

Lower

Does paternal CPA affect F2 generations?

Yes

Vinclozolin-treated adult males showed F0 with ____ Apoptosis rates

Increased