Mrs.

Ofelia Solano Saludar

Department of Natural Sciences University of St. La Salle

The female genital tract is specifically designed to: produce ova, accept sperm, control the process of fertilization, provide a site for implantation of the egg, provide essentials for fetal development to term

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Female Hypothalamus (Hypothalamic releasing factors) Hypophysis FSH Inhibin Mammary Glands Ovaries Estrogen Ovulation Corpus luteum - Progesterone LH Prolactin & Oxytocin

more ciliary activity of thicker & vascularized uterine endometrium uterine tube; build-up of sticky (G-Mucus) cervical mucosa uterine mucosa; watery inhibits HH axis cervical mucosa (E-mucus); Placenta secondary sexual characteristics; Chorionic gonadotropininhibits HH axis maintains corpus luteum SomatomammotropinFEMALE REPRODUCTIVE breast development

ENDOCRINOLOGY

PRIMATE MENSTRUAL CYCLE

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 PGCs arrive in female gonad at 3rd month, differentiate into oogonia, and divide by mitosis for a total of ~24 cell divisions.  By the 5th month, total # of cells reach maximum of 7 million.  Some oogonia mature to form 10 oocytes.  Continual decline until ovulation, menopause, death.

1. PRENATAL MATURATION

 Flat cells from surface a. Primordial and primary epithelium of ovary follicles (stromal cells) surround the 10 oocytes to form a primordial follicle.  Some oogonia and 10 oocytes degenerate (atresia) until the 7th month.  Remaining cells is estimated to be between 700,000 to 2 million.  Surviving oocytes enter meiosis I. Meiosis is arrested at diplotene.  By birth the complex of 10 oocyte and complete layers of follicle cells is called the primary follicle.

2.POSTNATAL MATURATION
 At puberty, approximately 40,000 cells survive; fewer than 500 will be ovulated; 5 to 15 primordial follicles mature with each ovarian cycle.  The oocyte undergoes a 500-fold increase in volume (10 m in a primordial follicle to 80 m in a fully developed follicle).  Concomitant with oocyte growth is an increase in the number of follicular granulosa cells, surrounded by stromal cells known as theca folliculi.

 The 10 follicle enlarges and develops into a preantral follicle, which is the first stage of FSH receptivity, as now the follicle has acquired FSH receptors.  Proliferation of granulosa cells is mediated by a paracrine factor, GDF9 or activin, of the TGFfamily, and enhanced by the actions of FSH.  Granulosa cells secrete growth and differentiation factors (TGFF2, VEGF, leptin, FGF2) that allow the oocyte to grow.  The oocyte maturation inhibitor (OMI), or meiotic inhibitory factor is secreted by follicular cells into the oocyte via gap junctions.  This arrest permits it to accumulate food reserves, mRNA, rRNA, cortical granules, morphogenetic factors, and protective chemicals (UV filters and DNA repair enzymes, distasteful chemicals, antibodies).

Granulosa cells and oocyte secrete glycoproteins on surface of oocyte, the zona pellucida.

b.Secondary follicle  Any follicular growth onward will require gonadotropin interaction with steroid hormones, and various peptides released by the dominant follicle.  Fluid-filled spaces appear between granulosa cells, coalesce & form the antrum, filled with a complex mixture of proteins, hormones, and other molecules synthesized or absorbed by the egg from other cells.  Nucleus (germinal vesicle) increases in size due to production of nuclear sap.  Amplification (oocyte lampbrush chromosomes) of gene copies for products needed in large quantities in the egg (mRNA, rRNA for chorion proteins) take place.

c.Tertiary, vesicular, or Graffian follicle Antrum enlarges; granulosa cells around oocyte forms cumulus oophorus. Oocyte is surrounded by the theca externa, the connective tissue which merges with the ovarian stroma; and the theca interna, which synthesize the enzyme aromatase converting theca-derived androgens to estrogens.

 Due to the presence of 5 -reductase, preantral and early antral follicles produce more androstenedione and testosterone in relation to estrogens.  5 -reductase is the enzyme responsible for converting testosterone to dihydrotestosterone (DHT). Once testosterone has been 5 -reduced, DHT cannot be aromatized and converted to estrogen.  However, the dominant follicle has high levels of CYP19 (aromatase), which enables it to secrete large quantities of estrogen, primarily estradiol.  The granulosa cells of this dominant follicle also secrete inhibin which suppresses FSH production.  Lateral inhibition, independence from FSH, and the shift form an androgenic to an estrogenic follicular microenvironment have significant effects in the selection of other follicles to become atretic.

 Microvilli of follicular cells and oocyte interdigitate in zona pellucida which forms the zona radiata.  Superficial layer of follicle cells on zona pellucida is referred to as the corona radiata.

 The LH surge of ovulation disrupts gap junction connections that releases meiotic inhibition, and allows the oocyte to resume meiosis II 10-12 hrs. before ovulation, with polar body I resting in its perivitelline space.  In some species, meiosis is modified such that a diploid egg is formed. These species can produce a new generation parthenogenetically, without fertilization.

 Due to the LH surge, prostaglandins and oxytocin, the female may experience the mild to moderate Mittelschmerz pain of ovulation, and a slight rise in basal body temperature (used in rhythm method of contraception).  At metaphase II, the ovum is ovulated surrounded by the zona pellucida and corona radiata.  Fertilization may now take place.

 If not fertilized within 24 hrs, the oocyte degenerates.  Granulosa lutein cells of the corpus luteum begin secreting progesterone for about 10 days.  If fertilization occurs, chorionic gonadotropin of the placental tissues maintains the corpus luteum. After the 2nd month, the placenta maintains pregnancy on its own.  If there is no fertilization, luteal cells regress due to apoptosis and luteolytic effects of prostaglandin F2.  Remnant body is called corpus albicans.  Reduction in progesterone secretion cause local hemorrhage (about 30 ml) and loss of integrity of areas of endometrium characteristic of menstruation..

OOCYTE DEVELOPMENTAL ARRESTS

Throughout its postnatal growth period, the oocyte remains in the dictyate (diplotene) stage. How does the egg break its dormancy and resume meiosis? Entry into the mitotic (M) phase of the cell cycle is regulated by mitosis-promoting factor (MPF). In the amphibian oocyte, it is generally thought that progesterone somehow converts a pre-MPF complex into active MPF. The mediator of the progesterone signal is the c-mos protein. Progesterone reinitiates meiosis by causing the egg to polyadenylate the maternal c-mos mRNA that has been stored in its cytoplasm, translating it into the cmos protein detectable only during oocyte maturation and is destroyed quickly upon fertilization.

 If the translation of c-mos is inhibited (by injecting cmos antisense mRNA into the oocyte), germinal vesicle breakdown & the resumption of oocyte maturation does not occur. The c-mos protein activates a phosphorylation cascade that phosphorylates and activates the p34 subunit of MPF. The active MPF allows the germinal vesicle to break down & the chromosomes to divide.

 However, the chromosomes then encounter a second block. MPF can take the chromosomes through only meiosis I & the prophase of the meiosis II. The oocyte is arrested again in the metaphase of meiosis II. This metaphase block is caused by the combined actions of c-mos & another protein, cyclin dependent kinase 2. These 2 proteins are subunits of cytostatic factor (CSF), which can block cell cycles in metaphase.

 The metaphase block is broken by fertilization. Evidence suggests that the Ca+2 influx attending fertilization enables the calcium-binding protein calmodulin to become active. Calmodulin, in turn, can activate 2 enzymes that inactivate CSF: calmodulin-dependent protein kinase II, which inactivates p34, and calpain II, a Ca+2-dependent protease that degrades cmos. Without CSF, cyclin can be degraded, and the meiotic division can be completed.

Schematic displaying meiosis and the genes whose function is known to be required for normal progression and completion of meiosis

Gonadotropins induce maturation by triggering activation of the MPF complex that includes the cell cycle regulators Cdc2, also known as Cdk1 and cyclin B. Before maturation, the MPF complex is maintained as an inactive phosphorylated pre-MPF complex. Map kinase is responsible for activation of the MPF and like MPF is maintained in an inactive state until maturation. MAPK activation during maturation promotes activity of Cdc25, a phosphatase that promotes activation of MPF and causes nuclear membrane dissolution.

ACCUMULATION OF CYTOPLASMIC FOOD RESERVES

Site of synthesis of egg proteins (phosvitin and lipovitellin), phospholipids and neutral fats, appear to be the liver. Radioactive 32P in disodium hydrogen phosphate was injected into the blood of laying hen; 6 hours after, radioactivity was highest in the liver, weakest in blood and growing oocytes; 12 hours later, detected radioactivity was in reverse order. Antigens in the growing oocytes of frogs are also found in the liver and the blood serum.

 In some animals, synthesis of yolk proteins occur inside oocyte. Production of yolk (vitellogenesis) result from activity of yolk nucleus of Balbiani lying at periphery of oocyte, and other organoids (ER, Golgi bodies, mitochondria). Mitochondrial protein kinase converts soluble partially phosphorylated phosvitin into insoluble fully phosphorylated protein Soluble components may be synthesized elsewhere (liver) and converted into insoluble forms inside oocyte.

TYPES OF EGG BASED ON YOLK CONTENT 1.Oligolecithal (small amounts) 2.Mesolecithal (Moderate amounts) 3.Centrolecithal (surface cytoplasm surround yolk at the center) 4.Telolecithal (large amounts of yolk)

ORGANIZATION OF THE EGG CYTOPLASM

Egg polarity is due to unequal distribution of egg substances: animal pole (nucleus) and vegetal pole (yolk) In amphibian eggs, the transition zone from a darkly pigmented animal pole to a light colored vegetal pole is called the marginal zone.

 Superficial layer of egg cytoplasm is known as the cortex, which fixes positions of parts of oocyte cytoplasm during periods of development.  It contains mucopolysaccharide-containing cortical granules, which play an important role at the time of fertilization.  Polar structure of egg is achieved by intrinsic factors in the oocyte itself, independent from the maternal body.

EGG ENVELOPES
1.Plasmalemma or cell membrane 2.Primary envelopes- develop between oocyte and follicle cells: vitelline envelope or membrane (amphibians, birds), chorion (fishes), zona pellucida (mammals), jelly coat (sea urchins). In later stages, the primary envelope develops the perivitelline space, a fluid-filled space between itself and the cytoplasm. 3.Secondary envelopessecreted by oviducts and genital organs 4.Jelly coat (amphibians) OR shell (sharks and rays)

   

Egg envelopes in Birds: Vitelline envelope (inner layer of rough fibers from ovary; outer layer from upper portion of fallopian tubes) Egg white (85% water, 15% albumins) Shell envelopes (2 layers: inner envelop adhere to egg white, outer envelope to shell) Shell CaCO3 Chalazae denser part of egg white that keeps egg in center of egg

How big is the egg?

DEVELOPING EGG & THE ENVIRONMENT 1. Aquatic forms take in water and mineral substances from environment. 2. Terrestial forms:  Some return to the water for egg laying or lay eggs in damp places.  Reptiles and birds developed cleidoic eggs (boxlike, development at the expense of substances stored inside the egg)

RETENTION OF EMBRYO INSIDE MOTHERS BODY OVIPARITY- egg-laying; contains yolk and albumen to support development VIVIPARITY- offspring is born alive EUVIVIPARITY- maternal tissues provide nutrition, e.g. histotrophic (embryotrophic) nutrition derived from glandular secretions, e.g. placenta OVOVIVIPARITY- egg provides nourishment throughout pregnancy, mother provides protection and oxygen; e.g. shark