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Fertilization, Pregnancy, Embryonic Development. Fertilization Human sperm fertilizable 48-72 h after ejac –Isthmic preparation Human ova fertilizable.

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Presentation on theme: "Fertilization, Pregnancy, Embryonic Development. Fertilization Human sperm fertilizable 48-72 h after ejac –Isthmic preparation Human ova fertilizable."— Presentation transcript:

1 Fertilization, Pregnancy, Embryonic Development

2 Fertilization Human sperm fertilizable h after ejac –Isthmic preparation Human ova fertilizable h after ov’n Ampulla Sperm hyaluronidase penetrates corona radiata

3 Ovum ZP3 –Glycoprotein –Recognition Sperm membr FA-1 –Prot receptor tyr kinase –Act’n  autophosph’n  cell prot phosph’n –  Act’n voltage gated Ca channels  AR Release, act’n acrosin (trypsin-like) –Penetration ZP

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5 Sperm head fuses w/ oocyte 2 nd Meiotic div’n –  Mature oocyte + polar body –Mech’s to prevent polyspermy Fusion male, female pronuclei  diploid zygote Mitosis  morula  blastocyst Blastocyst  uterus Implantation  dev’t chorion, placenta

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7 Implantation, Early Embryo Development Implantation begins 5-6 d after fert’n (d 21 cycle) –Completed 11 fert’n d –Coincides w/ peak prod’n progesterone by CL (midluteal) Progesterone impt to preparation decidual, secretory endometrium –If no fert’n, CL would begin decline now

8 Inner blastocyst cell mass  embryo proper Outer cells = trophoblasts –Contact, signal uterine epith EGF receptor on embryo nec Uterine cell cytokine (LIF) nec –Two cell pop’ns Syncytiotrophoblasts Cytotrophoblasts

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10 Syncytiotrophoblast – postmitotic surface layer –From fusion of cytotrophoblast plasma membr’s –Form initial chorionic shell Erodes endometrial capillaries, veins Perfused by maternal blood Cytotrophoblast – mitotic cells –Inner cells = Langhans or villous Form chorionic villi –Peripheral cells Form trophoblastic shell Form trophoblastic cell columns

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15 Syncytiotrophoblast cells secrete hCG  maternal circ’n –Detectable w/in 24 h beginning implantation –Incr’s w/ incr’d trophoblast cell mass (peak end 1 st trimester) –Functions: Stim’s luteal function Induces morning sickness –Stim area postrema of brain  n/v Stim’s fetal androgen secr’n –Impt to masculinization of fetal genitalia

16 hCG stim’s luteal function –Incr’s hormone prod’n at CL –Progesterone uninterrupted Mandatory until parturition –Functioning CL mandatory for maintenance first 7 wks At 5 wks after fert’n, placental prod’n progesterone sufficient sustained CL  strong neg feedback at ant pit Plasma FSH, LH suppressed Gonadotrophs unresponsive to GnRH

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18 Chorionic villi dev by 2 nd week after fert’n –Blood vessels here Spiral endometrial arteries –Anchors to endometrium, placenta –Development her  umbilical cord Definitive placenta at fert’n wk –Structures can withstand high maternal blood pressure –Incr’d placental perfusion correlates w/ peak plasma hCG concent’s

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21 Placenta Interface between maternal, fetal tissues –Maternal = decidua Endometrial lining Falls off at parturition Supplied by spiral arteries –Fetal cells = trophoblasts Exchange organ Barrier

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25 “Incomplete twin of fetus” –GI, lung, kidney –Immunologic Transfer immunoglobulins (exc IgG) Prevent fetus rejection –Endocrine Synth hormones, binding prot’s Transport hormones Degrade hormones

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27 Placenta secretes variant of GH –GH-V –Replaces maternal w gestation –May promote fetal growth –May be impt to pancreatic islet cells Causes rising plasma IGF-1 –Neg feedback  suppression pit GH

28 Fetoplacental Unit Sim to theca lutein, granulosa lutein cooperation in progesterone/E2 production 3 Main hormonal groups –Estrogens –Progesterone –Corticosteroids

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30 Estrogens –From androgens by fetal adrenal cortex –Fetus doesn’t express 3  hydroxysteroid dehydrogenase (isomerase) So all pregnenolone  dehydroepiandrosterone (DHEA) –Placenta doesn’t express p450C17 Can’t make 17-OH progesterone Can’t make androstenedione Can’t make DHEA –Impt to protection female fetus from androgens –Placenta makes mostly estriol Sensitizes uterine smooth muscle to oxytocin

31 Progesterone –Syncytiotrophoblasts synth de novo From cholesterol derived from maternal plasma –Placenta expresses much p450scc Tubulovesicular mitochondria Placenta can’t synthesize cholesterol Pregnenolone  progesterone –Placenta doesn’t express p450C17 So only progesterone –Enters both fetal, maternal circulations

32 Corticosteroids –In fetus, progesterone is precursor to adrenocortical hormones –Glucocorticoids Gen’ly growth inhibitors, so minimized Placental enz’s break down maternal glucocort’s –Uses maternal ACTH at fetal adrenal cortex –Diff enzymes diff dev’l stages –25 th gestational week, rising corticosteroids Impt to feedback mech’s Impt to organ maturation

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35 Embryonic Development/ Endocrinology Innate bisexual potential  decision to male or female Sex determination –Chromosomal (Y=male) –Gonadal (testis=male) –Genal (external genitalia) –Sexual/gender identity (psychosocial) –Sexual orientation (attraction)

36 Chromosomal Sex Established during fert’n Fusion male/female pronuclei  diploid chromosomal # Oocyte – X sex chromosome Sperm – X or Y sex chromosome –Female normal karyotype 46,XX –Male normal karyotype 46,XY

37 Gonadal Sex Established during embryonic development –5 th week – urogenital ridge dev’d Adjacent adrenal gland –6 th week – indifferent gonad from urogenital ridge Requires expression WT-1 gene  zinc-finger transcription factor –Nec for gonad, kidney expression (mice) Requires expression Steroidogenic Factor-1 (SF-1)

38 SF-1 –Impt to induction steroidogenic enz’s (mice) –Impt to dev’t adrenal glands, gonads, ventromedial nucleus hypothal (mice) –Impt to dev’t testis from indiff gonad Stim’s testic differentiation  Sertoli cell appearance Stim’s Sertoli prod’n AMH = AntiMullerian Hormone = MIF Stim’s expression steroidogenic enzymes by dev’ng Leydig cells

39 Testis Development Mandatory expression Sex determining Region Y (SRY gene)  SRY transcription factor (= Testis Determining Factor (TDF)) –Related to SOX genes that are impt to development cartilage, testis SRY transcription factor probably suppresses Dosage Sensitive Sex reversal (DSS) gene –DSS suppresses SF1 –So SRY  disinhibition SF-1

40 Now SF-1  testicular differentiation –Sertoli cells –Steroidogenic enz’s in Leydig cells –AMH Mullerian ducts would dev into female tract AMH  inhibition dev’t Mullerian ducts

41 Sertoli Cells in Developing Testis Secr’s AMH –43-50 d embryonic life –Paracrine –  Involution Mullerian duct Absence AMH  Mullerian duct dev’t regardless of sex steroid env –  Fallopian tubes, uterus, upper vagina –Normal condition in females

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43 Leydig Cells in Developing Fetus Secrete testosterone from embryonic d 60 (wk 8-9) Not yet controlled by hypothal-hypophyseal system hCG crucial –Rising during 1 st trimester –Declines after wk 12 –Stim’s synth testosterone in developing Leydig cells

44 Testosterone –Stim’s dev’t Wolffian duct structures Give rise to epididymis, vas deferens, seminal vesicles –Must be present before embryo wk 12 –Must be converted to DHT for masculinization external genitalia, prostate dev’t

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46 Fetal Gonad Sex Steroid Synthesis 17  hydroxylase activity dominant –Pregnenolone  17  hydroxypregnenolone and 17  hydroxyprogesterone –  androgen synth Testes  testosterone Ovary  androstenedione, testosterone precursors for estrogen –  Estradiol


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