Spermatogenesis: Formation of Sperm

• Gametogenesis is the process of gamete formation, producing sperm and egg through Meiosis II.

Types of Gametogenesis:

• Spermatogenesis
• Oogenesis

Spermatogenesis

• Spermatogenesis is the formation of spermatozoa from primordial germ cells (PGCs)/spermatogonia located in the seminiferous tubules of the testes.
• PGCs remain dormant in the seminiferous tubules until puberty, when they undergo divisions to form spermatogonia.
• Spermatogenesis occurs in the seminiferous tubules of the testes.
• This process starts after puberty and continues throughout old age.
• The duration is 64-74 days.

Stages of Spermatogenesis:

• Spermatocytogenesis involves PGCs undergoing a series of mitotic divisions to form numerous spermatogonia.
• Three types of spermatogonia distinguished: dark type A, light type A, and type B.

Spermatocytosis

• PGCs divide by mitosis to form dark type A spermatogonia, which act as stem cells.
• Each dark type A spermatogonium undergoes mitosis to form one dark A spermatogonium and one light type A spermatogonium.
• Dark type A spermatogonia are reserved for the repetition of the cycle.
• Light type A spermatogonia undergo mitotic division to form two dark type B spermatogonia.
• Type B spermatogonium undergoes mitotic division to form two primary spermatocytes, which are the largest germ cells.

Meiotic Divisions

• Primary spermatocytes undergo the first meiotic division (reductional division) to form two secondary spermatocytes, each with a haploid number of chromosomes.
• Secondary spermatocytes immediately undergo the second meiotic division (mitotic division) to form two spermatids, each with a haploid number of chromosomes.
• A primary spermatocyte produces four haploid spermatids through meiotic division.
• Spermatids are small cells, about half the size of secondary spermatocytes, with round, darkly stained nuclei located close to the lumen of the seminiferous tubule.
• Each spermatid changes to become spermatozoon or sperm, in a transformation called spermiogenesis.

Hormone Regulation

• Testosterone, secreted by Leydig cells, is the hormone responsible for spermatogenesis.

Spermatozoa Formation

• One primary spermatocyte forms four spermatozoa: two with 22 autosomes and one X chromosome each and two with 22 autosomes and one Y chromosome each.

Spermiogenesis

• Spermiogenesis transforms spermatids into mature spermatozoa.
• During spermiogenesis, the spermatid, a circular cell with a nucleus, Golgi apparatus, centrosome, and mitochondria, transforms into a spermatozoon.
• Nuclear material (chromatin) condenses, and the nucleus moves to one pole to form the head of the spermatozoon.
• The Golgi apparatus forms the acrosomal cap that covers the anterior two-thirds of the nucleus.
• The centrosome divides into two centrioles.
• One centriole moves to the posterior end of the nucleus to occupy the neck region, giving rise to the axial filament.
• The other centriole moves away and becomes ring-shaped, forming an annulus around the distal end of the middle piece.
• The part of the axial filament between the neck and annulus is surrounded by mitochondria to form the middle piece.
• The remaining axial filament elongates to form the principal and end pieces or tail.
• Most of the cytoplasm is shed off, but the cell membrane covers the entire spermatozoon.

Spermatozoon Structure

• The spermatozoon (50 μm in length) has a head, neck, and tail.
• The tail is further divided into the middle piece, principal piece, and end piece; it forms four-fifths of the total length.

Spermatozoon Head

• The head is shaped like a spearhead and mainly contains a nucleus with condensed chromatin (DNA).
• The anterior two-thirds of the nucleus is covered by an acrosomal cap containing enzymes like hyaluronidase and acrosin.

Spermatozoon Neck

• The neck is narrow and contains a funnel-shaped basal plate and a centriole that gives rise to the axial filament extending through the tail.

Spermatozoon Tail

• The tail has three parts: middle piece, principal piece, and end piece.
• The middle piece contains the axial filament surrounded by a spirally arranged mitochondrial sheath, with the annulus at its distal end.
• The principal piece comprises the axial filament covered by seven outer dense fibers.
• The end piece consists only of the axial filament.
• Axial filament is responsible for the movements of the spermatozoon, and mitochondria supply energy for these movements.

Clinical Correlations: Abnormal Sperms

• Abnormal sperms are more common, has two parts head and tail.

Types of Abnormalities

• Morphological abnormalities include abnormal head and tail shapes two heads or tails, giant or dwarf sperms, and joined sperms.
• For potential fertility, 50% of sperms should be motile after 2 hours of ejaculation, and some should be motile after 24 hours.
• Genetic abnormalities involve sperm having abnormal chromosomal content and are rare compared to oocytes.

Oogenesis

• Oogenesis is the process of forming female gametes (oocytes) from PGCs.
• Oogenesis begins long before birth in the cortex of the ovary and before birth PGCs divide by mitosis to form numerous oogonia.
• Each oogonium enlarges into a primary oocyte, which enters the prophase of the first meiotic division before birth and is arrested due to an oocyte maturation inhibitor (OMI) secreted by follicular cells.

At Puberty

• At puberty, in each ovarian cycle, 5-50 primary oocytes resume the first meiotic division just before ovulation.
• This division forms two daughter cells (secondary oocyte and first polar body), each with a haploid number of chromosomes.
• The first meiotic division is unequal; most cytoplasm goes to the secondary oocyte, while the other forms the first polar body.

After Fertilization

• The secondary oocyte begins the second meiotic division at ovulation, completing it only after sperm penetration (fertilization).
• The second meiotic division is also unequal, forming an ovum (mature oocyte) with most of the cytoplasm and a second polar body with very little cytoplasm.
• One primary oocyte forms one ovum with 22 autosomes and one X chromosome and three polar bodies each with 22 autosomes and one X chromosome.
• The primary oocyte begins the first meiotic division before birth and completes it at puberty just before ovulation.
• Primary oocytes are not formed after birth and the secondary oocyte is in the metaphase stage of the second meiotic division at ovulation, completing it only if fertilization occurs.
• At birth, the ovary contains about two million germ cells.
• By puberty, around 40,000 oocytes remain, as most degenerate and oogenesis is accompanied by the development and growth of ovarian follicles.

Development of Ovarian Follicles

• The oogonium is covered by a single layer of flat epithelial (follicular) cells from the stromal cells of the ovary or from the surface epithelium to form a primordial follicle.
• The oogonium within the follicle contains a single, large nucleus with a prominent eccentric nucleolus.

Steps of Forming Ovarian Follicles

• Flattened follicular cells become columnar, forming a unilaminar primary follicle.
• Follicular cells proliferate to form several layers of membrana granulosa, now called granulosa cells.
• The primary oocyte and granulosa cells secrete a glycoprotein substance forming the zona pellucida, a thick membrane between the cells.
• Granulosa cells rest on a basement membrane separating them from stromal cells, forming a multilaminar (maturing) primary follicle.
• Small fluid-filled cavities appear between follicular cells, fusing to form a large cavity (antral cavity/antrum), and the follicle becomes a secondary (vesicular) follicle.
• The antrum increases in size, pushing the oocyte to one side.
• Granulosa cells surrounding the oocyte are called cumulus oophoricus (or cumulus ovaricus).
• Granulosa cells attaching the oocyte to the follicle wall are called discus proligerus.
• Stromal cells around the granulosa cells condense to form the theca interna (theca = covering).
• Fibrous tissues outside the theca interna condense to form the theca externa, making the ovarian follicle fully matured.

Ovulation

• Ovulation involves shedding an ovum from the ovary.
• The Graafian follicle enlarges, reaching the ovary surface and forming a bulge.
• The theca and stroma on the follicle side become thin and an avascular area (stigma) appears at the most convex superficial position.
• Cells of cumulus oophoricus loosen with intercellular fluid accumulation and ultimately the follicle ruptures when the ovum is released from the ovary (ovulation).
• The expelled secondary oocyte is surrounded by the zona pellucida and radially arranged follicular cells termed corona radiata.
• The fimbriated end of the uterine tube picks up the oocyte and puts it into the lumen of the uterine tube.
• The empty Graafian follicle becomes the corpus luteum which lasts for 10–12 days if the ovum is not fertilized, and 2-3 months if fertilization and pregnancy occurs.
• Graafian follicle cells secrete estrogen, while corpus luteum cells secrete progesterone.

Structure of Secondary Oocyte

• The secondary oocyte is large (more than 100 µm in diameter) and sheds from the ovary.
• It undergoes a second meiotic division to shed the second polar body.
• No nucleus is seen as the nuclear membrane dissolves for the second meiotic division.
• Spindle and chromosomes attach to the equatorial plane (metaphase stage).
• The oocyte is surrounded by the zona pellucida which is then surrounded by corona radiata cells.
• Perivitelline space is present between the cell membrane (vitelline membrane) and zona pellucida; it contains the first polar body from the first meiotic division.

Clinical Correlations: Oocytes

• Oocytes may be binucleated or trinucleated; but they usually degenerate before maturity.
• Oocytes with abnormal chromosomal contents may occur due to nondisjunction in meiosis I or II, resulting in oocytes with 24 or 22 chromosomes instead of 23.
• An oocyte with 24 chromosomes fertilized by a normal sperm (23 chromosomes) yields a zygote with 47 chromosomes (trisomy).
• Trisomy 21 (Down's syndrome) is the most common trisomy and an ovum with 22 chromosomes fertilized by a normal sperm (23 chromosomes) yields a zygote with 45 chromosomes (monosomy), such as Turner's syndrome (45, Xo).