The Female Reproductive System: Hormonal 27 The Female Reproductive System: Hormonal

The mammary glands – pp. 1047 – 1048 Female Reproductive System – Hormonal Regulation & Aspects Related to Hormonal Control The ovaries – pp104 – 1042 The endometrium – p. 1044 The mammary glands – pp. 1047 – 1048 Physiology of the female reproductive system – pp. 1049 – 1058

Female Reproductive System Breast – mammary glands Ovaries and follicle development

Mammary Glands Modified sweat glands consisting of 15–25 lobes Areola: pigmented skin surrounding the nipple Suspensory ligaments: attach the breast to underlying muscle Lobules within lobes contain glandular alveoli that produce milk

Mammary Glands Milk  lactiferous ducts  lactiferous sinuses  open to the outside at the nipple

Pectoralis major muscle Suspensory ligament First rib Skin (cut) Pectoralis major muscle Suspensory ligament Adipose tissue Lobe Areola Nipple Opening of lactiferous duct Lactiferous sinus Lactiferous duct Lobule containing alveoli Hypodermis (superficial fascia) Intercostal muscles (a) (b) Figure 27.15

Breast Cancer: Detection and Treatment 70% of women with breast cancer have no known risk factors Early detection via self-examination and mammography Treatment depends upon the characteristics of the lesion: Radiation, chemotherapy, and surgery followed by irradiation and chemotherapy

(a) Mammogram procedure Malignancy (b) Film of normal breast (c) Film of breast with tumor Figure 27.16

Usually arises from the epithelial cells of small ducts Breast Cancer Usually arises from the epithelial cells of small ducts Risk factors include: Early onset of menstruation and late menopause No pregnancies or first pregnancy late in life Family history of breast cancer 10% are due to hereditary defects, including mutations to the genes BRCA1 and BRCA2

Production of female gametes Begins in the fetal period Oogenesis Production of female gametes Begins in the fetal period Oogonia (2n ovarian stem cells) multiply by mitosis and store nutrients Primary oocytes develop in primordial follicles Primary oocytes begin meiosis but stall in prophase I

Ovaries (oogenesis) Follicle Immature egg (oocyte) surrounded by Follicle cells (one cell layer thick) Granulosa cells (when more than one layer is present)

Several stages of development Follicles Several stages of development Primordial follicle: squamouslike follicle cells + oocyte Primary follicle: cuboidal or columnar follicle cells + oocyte Secondary follicle: two or more layers of granulosa cells + oocyte Late secondary follicle: contains fluid-filled space between granulosa cells; coalesces to form a central antrum

Vesicular (Graafian) follicle Ovaries Vesicular (Graafian) follicle Fluid-filled antrum forms; follicle bulges from ovary surface Ovulation Ejection of the oocyte from the ripening follicle Corpus luteum develops from ruptured follicle after ovulation

Late secondary follicle Degenerating corpus luteum (corpus albicans) Tunica albuginea Oocyte Granulosa cells Late secondary follicle Degenerating corpus luteum (corpus albicans) Cortex Mesovarium and blood vessels Germinal epithelium Vesicular (Graafian) follicle Primary follicles Antrum Oocyte Ovarian ligament Zona pellucida Theca folliculi Medulla Ovulated oocyte Corpus luteum Developing corpus luteum Corona radiata (a) Diagrammatic view of an ovary sectioned to reveal the follicles in its interior Figure 27.11a

Each month after puberty, a few primary oocytes are activated Oogenesis Each month after puberty, a few primary oocytes are activated One is selected each month to resume meiosis I Result is two haploid cells Secondary oocyte First polar body

The secondary oocyte arrests in metaphase II and is ovulated Oogenesis The secondary oocyte arrests in metaphase II and is ovulated If penetrated by sperm the second oocyte completes meiosis II, yielding Ovum (the functional gamete) Second polar body

Figure 27.17 Meiotic events Follicle development in ovary Before birth Oogonium (stem cell) Follicle cells Mitosis Oocyte Primary oocyte Primordial follicle Growth Infancy and childhood (ovary inactive) Primary oocyte (arrested in prophase I; present at birth) Primordial follicle Each month from puberty to menopause Primary follicle Primary oocyte (still arrested in prophase I) Secondary follicle Spindle Vesicular (Graafian) follicle Meiosis I (completed by one primary oocyte each month in response to LH surge) Secondary oocyte (arrested in metaphase II) First polar body Ovulation Meiosis II of polar body (may or may not occur) Sperm Ovulated secondary oocyte Meiosis II completed (only if sperm penetration occurs) In absence of fertilization, ruptured follicle becomes a corpus luteum and ultimately degenerates. Polar bodies (all polar bodies degenerate) Second polar body Ovum Degenating corpus luteum Figure 27.17

Monthly series of events associated with the maturation of an egg Ovarian Cycle Monthly series of events associated with the maturation of an egg Two consecutive phases (in a 28-day cycle) Follicular phase: period of follicle growth (days 1–14) Ovulation occurs midcycle Luteal phase: period of corpus luteum activity (days 14–28)

Primordial follicle becomes primary follicle Follicular Phase Primordial follicle becomes primary follicle The primordial follicle is activated Squamouslike cells become cuboidal Follicle enlarges to become a primary (1) follicle

Primordial follicles 1 Theca folliculi Primary oocyte Zona pellucida 3 4 2 Primary oocyte 1 Zona pellucida Antrum Secondary oocyte 5 1 Primordial follicles 8 6 Secondary oocyte 7 Corona radiata Figure 27.18 (1 of 7)

Primary follicle 2 Theca folliculi Primary oocyte Zona pellucida 3 4 2 Primary oocyte 1 Zona pellucida Antrum Secondary oocyte 5 Primary follicle 2 8 6 Secondary oocyte Corona radiata 7 Figure 27.18 (2 of 7)

Follicular Phase Primary follicle becomes a secondary follicle Stratified epithelium (granulosa cells) forms around oocyte Granulosa cells and oocyte guide one another’s development

Follicular Phase Secondary follicle becomes a late secondary follicle Connective tissue (theca folliculi) and granulosa cells cooperate to produce estrogens Zona pellucida forms around the oocyte Fluid begins to accumulate

Secondary follicle 3 Theca folliculi Primary oocyte Zona pellucida 4 2 Primary oocyte 1 Zona pellucida Antrum Secondary oocyte 5 3 Secondary follicle 8 6 Secondary oocyte 7 Corona radiata Figure 27.18 (3 of 7)

Theca folliculi Primary oocyte Zona pellucida Antrum Secondary oocyte 3 4 2 Primary oocyte 1 Zona pellucida Antrum Secondary oocyte 5 8 6 Secondary oocyte 4 Late secondary follicle 7 Corona radiata Figure 27.18 (4 of 7)

Follicular Phase Late secondary follicle becomes a vesicular follicle Antrum forms and expands to isolate the oocyte with its corona radiata on a stalk Vesicular follicle bulges from the external surface of the ovary The primary oocyte completes meiosis I

Ovulation Ovary wall ruptures and expels the secondary oocyte with its corona radiata Mittelschmerz: twinge of pain sometimes felt at ovulation 1–2% of ovulations release more than one secondary oocyte, which, if fertilized, results in fraternal twins

Theca folliculi Primary oocyte Zona pellucida Antrum Secondary oocyte 3 4 2 Primary oocyte 1 Zona pellucida Antrum Secondary oocyte Mature vesicular follicle carries out meiosis I; ready to be ovulated 5 5 8 6 Secondary oocyte Corona radiata 7 Figure 27.18 (5 of 7)

Follicle ruptures; secondary oocyte ovulated Theca folliculi 3 4 2 Primary oocyte 1 Zona pellucida Antrum Secondary oocyte 5 6 Follicle ruptures; secondary oocyte ovulated 8 6 Secondary oocyte 7 Corona radiata Figure 27.18 (6 of 7)

Luteal Phase Ruptured follicle collapses Granulosa cells and internal thecal cells form corpus luteum Corpus luteum secretes progesterone and estrogen

Luteal Phase If no pregnancy, the corpus luteum degenerates into a corpus albicans in 10 days If pregnancy occurs, corpus luteum produces hormones until the placenta takes over at about 3 months

Corpus luteum (forms from ruptured follicle) Theca folliculi 3 4 2 Primary oocyte 1 Zona pellucida Antrum Secondary oocyte 5 7 Corpus luteum (forms from ruptured follicle) 8 6 Secondary oocyte 7 Corona radiata Figure 27.18 (7 of 7)

Establishing the Ovarian Cycle During childhood, ovaries grow and secrete small amounts of estrogens that inhibit the hypothalamic release of GnRH As puberty nears, GnRH is released; FSH and LH are released by the pituitary, and act on the ovaries These events continue until an adult cyclic pattern is achieved and menarche occurs

Establishing the Ovarian Cycle During childhood, until puberty Ovaries secrete small amounts of estrogens Estrogen inhibits release of GnRH

Establishing the Ovarian Cycle At puberty Leptin from adipose tissue decreases the estrogen inhibition GnRH, FSH, and LH are released In about four years, an adult cyclic pattern is achieved and menarche occurs

Hormonal Interactions During a 28-Day Ovarian Cycle Day 1: GnRH  release of FSH and LH FSH and LH  growth of several follicles, and estrogen release  estrogen levels Inhibit the release of FSH and LH Stimulate synthesis and storage of FSH and LH Enhance further estrogen output

Hormonal Interactions During a 28-Day Ovarian Cycle Estrogen output by the vesicular follicle increases High estrogen levels have a positive feedback effect on the pituitary at midcycle Sudden LH surge at day 14

Hormonal Interactions During a 28-Day Ovarian Cycle Effects of LH surge Completion of meiosis I (secondary oocyte continues on to metaphase II) Triggers ovulation Transforms ruptured follicle into corpus luteum

Hormonal Interactions During a 28-Day Ovarian Cycle Functions of corpus luteum Produces inhibin, progesterone, and estrogen These hormones inhibit FSH and LH release Declining LH and FSH ends luteal activity and inhibits follicle development

Hormonal Interactions During a 28-Day Ovarian Cycle Days 26–28: corpus luteum degenerates and ovarian hormone levels drop sharply Ends the blockade of FSH and LH The cycle starts anew

Early and midfollicular phases Hypothalamus Hypothalamus 5 GnRH Positive feedback exerted by large in estrogen output. 4 8 Travels via portal blood 1 Anterior pituitary 1 5 Progesterone Estrogen Inhibin LH surge FSH LH Ruptured follicle 6 2 2 8 Slightly elevated estrogen and rising inhibin levels. 3 7 Thecal cells Granulosa cells Androgens Corpus luteum Mature follicle Ovulated secondary oocyte Convert androgens to estrogens Inhibin 2 Late follicular and luteal phases Early and midfollicular phases Figure 27.19

(a) Fluctuation of gonadotropin levels: Fluctuating LH FSH (a) Fluctuation of gonadotropin levels: Fluctuating levels of pituitary gonadotropins (follicle-stimulating hormone and luteinizing hormone) in the blood regulate the events of the ovarian cycle. Figure 27.20a

(b) Ovarian cycle: Structural changes in the ovarian Primary follicle Vesicular follicle Corpus luteum Degenerating corpus luteum Secondary follicle Ovulation Follicular phase Ovulation (Day 14) Luteal phase (b) Ovarian cycle: Structural changes in the ovarian follicles during the ovarian cycle are correlated with (d) changes in the endometrium of the uterus during the uterine cycle. Figure 27.20b

Uterine (Menstrual) Cycle Cyclic changes in endometrium in response to ovarian hormones Three phases Days 1–5: menstrual phase Days 6–14: proliferative (preovulatory) phase Days 15–28: secretory (postovulatory) phase (constant 14-day length)

Uterine Cycle Menstrual phase Ovarian hormones are at their lowest levels Gonadotropins are beginning to rise Stratum functionalis is shed and the menstrual flow occurs

Uterine Cycle Proliferative phase Estrogen levels prompt generation of new functional layer and increased synthesis of progesterone receptors in endometrium Glands enlarge and spiral arteries increase in number

Uterine Cycle Secretory phase Progesterone levels prompt Further development of endometrium Glandular secretion of glycogen Formation of the cervical mucus plug

(c) Fluctuation of ovarian hormone levels: Estrogens Progesterone (c) Fluctuation of ovarian hormone levels: Fluctuating levels of ovarian hormones (estrogens and progesterone) cause the endometrial changes of the uterine cycle. The high estrogen levels are also responsible for the LH/FSH surge in (a). Figure 27.20c

Stratum functionalis (functional layer) Endometrium Stratum functionalis (functional layer) Changes in response to ovarian hormone cycles Is shed during menstruation Stratum basalis (basal layer) Forms new functionalis after menstruation Unresponsive to ovarian hormones

Spiral (coiled) artery Lumen of uterus Epithelium Capillaries Uterine glands Venous sinusoids Lamina propria of connective tissue Spiral (coiled) artery Straight artery Endometrial vein Smooth muscle fibers Radial artery Arcuate artery Uterine artery (b) Figure 27.13b

Spiral (coiled) artery Lumen of uterus Epithelium Capillaries Uterine glands Venous sinusoids Lamina propria of connective tissue Spiral (coiled) artery Straight artery Endometrial vein Smooth muscle fibers Radial artery Arcuate artery Uterine artery (b) Figure 27.13b

(d) The three phases of the uterine cycle: Endometrial glands Blood vessels Menstrual flow Functional layer Basal layer Days Menstrual phase Proliferative phase Secretory phase (d) The three phases of the uterine cycle: • Menstrual: Shedding of the functional layer of the endometrium. • Proliferative: Rebuilding of the functional layer of the endometrium. • Secretory: Begins immediately after ovulation. Enrichment of the blood supply and glandular secretion of nutrients prepare the endometrium to receive an embryo. Both the menstrual and proliferative phases occur before ovulation, and together they correspond to the follicular phase of the ovarian cycle. The secretory phase corresponds in time to the luteal phase of the ovarian cycle. Figure 27.20d

If fertilization does not occur Uterine Cycle If fertilization does not occur Corpus luteum degenerates Progesterone levels fall Spiral arteries kink and spasm Endometrial cells begin to die Spiral arteries constrict again, then relax and open wide Rush of blood fragments weakened capillary beds and the functional layer sloughs

Effects of Estrogens Promote oogenesis and follicle growth in the ovary Exert anabolic effects on the female reproductive tract Support the rapid but short-lived growth spurt at puberty

Induce secondary sex characteristics Effects of Estrogens Induce secondary sex characteristics Growth of the breasts Increased deposit of subcutaneous fat (hips and breasts) Widening and lightening of the pelvis

Effects of Estrogens Metabolic effects Maintain low total blood cholesterol and high HDL levels Facilitates calcium uptake

Effects of Progesterone Progesterone works with estrogen to establish and regulate the uterine cycle Effects of placental progesterone during pregnancy Inhibits uterine motility Helps prepare the breasts for lactation