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Spermatogenesis

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Part of the book series: Endocrinology ((ENDOCR))

Abstract

Production of male gametes, i.e., spermatogenesis, takes place in the seminiferous tubules of the testis. It is a multifaceted, process that takes 2.5 months to complete in man and results in formation of the most highly specialized cell type in the human body, the sperm. The seminiferous epithelium is in constant turnover as new generations of germ cells start to differentiate on the basal lamina and mature gametes are released from the apical part to the tubular lumen. Different generations of germ cells ensue spermatogenesis in synchrony and therefore over a period of time, called the cycle, the seminiferous epithelium has the same appearance. Ability to produce sperm spans the lifetime of sexually mature males and ultimately depends on germ-line stem cell (GSC) self-renewal. GSCs are maintained in a niche created by somatic cells and tissue microenvironment. Transmission of genetic information to subsequent generations and perpetuation of the species ultimately depend on GSC maintenance and the delicate balance between GSC self-renewal and differentiation. Spermatogenesis needs to be kept at a quantitatively normal level to sustain male fertility. Sertoli cells are the somatic component of the seminiferous epithelium, and they create the microenvironment that enables germ cells to survive, proliferate, and differentiate. Sertoli cells show unparalleled plasticity in gene expression and function during development and across the cycle of the seminiferous epithelium, and germ cells are dependent on management of their differentiation by Sertoli cells. Sertoli cells are targets of pituitary-derived follicle-stimulating hormone (FSH) and testosterone, produced in Leydig cells of testicular interstitium under control of luteinizing hormone (LH), and they transduce these signals and other stimuli into paracrine regulation of spermatogenesis and coordinate gene expression in germ cells. The transcriptome of male germ cells presents one of the widest among all cell types including not only thousands of protein-coding RNAs but also a wide range of short noncoding RNAs that play a pivotal role in posttranscriptional control of gene expression. Many hormones and factors control spermatogenesis and GSC maintenance, but testosterone, retinoic acid (RA), and FSH action are needed to optimize sperm production. FSH mainly affects premeiotic germ cells, whereas testosterone and RA act throughout male germ cell differentiation. However, quantitatively and qualitatively normal spermatogenesis requires all of them.

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Abbreviations

Aal4-16 :

Undifferentiated spermatogonia A-aligned 4-16

ABP:

Androgen-binding protein

Adark :

Type A-dark spermatogonia

Adifferentiating :

Differentiating type A spermatogonia

AKT:

AKT serine/threonine kinase 1

AMH:

Anti-Müllerian hormone

AP1:

Activator protein 1

Apale :

Type A-pale spermatogonia

Apr :

Undifferentiated spermatogonia A-paired

Aprogenitor :

Progenitor type A spermatogonia

AR:

Androgen receptor

ARE:

Androgen responsive element

As :

Undifferentiated spermatogonia A-single

Astem :

Stem type A spermatogonia

Atransition :

Transitional type A spermatogonia

Aundiff :

Undifferentiated type A spermatogonia

BAX:

BCL2 associated X

BCL6b:

B-cell CLL/lymphoma 6B

BCL-W:

BCL2 like 2

BCL-XL:

BCL2-like 1

BMP4:

Bone morphogenetic protein 4

BMPR:

Bone morphogenetic protein receptor

cAMP:

Cyclic adenosine monophosphate

CCND1:

Cyclin D1

CCND3:

Cyclin D3

CK18:

Cytokeratin 18

CREB:

cAMP response element-binding

CSF1:

Colony stimulating factor 1

CSF1R:

Colony stimulating factor 1 receptor

CXCL12:

C-X-C motif chemokine ligand 12

CXCR4:

C-X-C motif chemokine receptor 4

DHH:

Desert hedgehog

DMRT1:

Doublesex and mab-3 related transcription factor 1

DNMT3a/b:

DNA methyltransferase 3 alpha/beta

E2F3:

E2F transcription factor 3

ERa/b:

Estrogen receptor alpha/beta

ERM:

Ets-related molecule

ESYT3:

Extended synaptotagmin 3

FGF2:

Fibroblast growth factor 2

FGFR:

Fibroblast growth factor receptor

FOXL2:

Forkhead box L2

FOXO1:

Forkhead box O1

FSH:

Follicle stimulating hormone

FSHR:

Follicle stimulating hormone receptor

FST:

Follistatin

G0 :

G zero phase

GDNF:

Glial cell derived neurotrophic factor

GFRa1:

GDNF family receptor alpha 1

GJA6:

Gap junction protein, alpha 6

GnRH:

Gonadotropin releasing hormone

GSC:

Germ-line stem cell

hCG:

Human chorionic gonadotropin

ID4:

Inhibitor of DNA binding 4

IGF1:

Insulin-like growth factor 1

IL-1b:

Interleukin 1 beta

INHA:

Inhibin alpha

INHBB:

Inhibin beta B

ITT:

Intratesticular testosterone

KIT:

KIT proto-oncogene receptor tyrosine kinase

LC:

Leydig cell

LH:

Luteinizing hormone

LHCGR:

Luteinizing hormone/choriogonadotropin receptor

LHR:

Luteinizing hormone receptor

LHX1:

LIM homeobox 1

LuRKO:

Luteinizing hormone receptor knockout

MAP2K1:

Mitogen-activated protein kinase kinase 1

MAPK:

Mitogen-activated protein kinase

MCF2:

MCF.2 cell line derived transforming sequence

miR221/2:

microRNA 221/2

miRNA:

microRNA

mRNA:

Messenger RNA

mTORC1:

Mammalian target of rapamycin complex 1

NANOS2:

Nanos C2HC-type zinc finger 2

NF-kB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NGN3:

Neurogenin 3

NR5a2:

Nuclear receptor subfamily 5 group A member 2

NXF3:

Nuclear RNA export factor 3

PDK1:

Pyruvate dehydrogenase kinase 1

PGC:

Primordial germ cell

PI3-K:

Phosphoinositide 3-kinase

PKA:

Protein kinase A

PLZF:

Promyelocytic leukemia zinc finger

PTCH:

Patched

PTM:

Peritubular myoid cell

RA:

Retinoic acid

RARg:

Retinoic acid receptor gamma

RB:

Retinoblastoma protein

Redd1:

Regulated in development and DNA damage 1

Ret:

Rearranged during transfection

RHOX5:

Reproductive homeobox 5

RXRb:

Retinoid X receptor beta

SALL4:

Spalt-like transcription factor 4

SCF:

Stem cell factor

SMAD2/3:

SMAD family member 2/3

SOHLH1/2:

Spermatogenesis and oogenesis specific basic helix-loop-helix 1/2

SOX3:

SRY-box 3

SOX9:

SRY-box 9

SRY:

Sex determining region Y

SSC:

Spermatogonial stem cell

SSPC:

Spermatogonial stem and progenitor cell

STRA8:

Stimulated by retinoic acid gene 8

T:

Testosterone

TAF4b:

TATA-box binding protein associated factor 4b

TF:

Transferrin

TFIID:

Transcription factor II D

TGFb:

Transforming growth factor beta

TGFb2:

Transforming growth factor beta 2

TNFa:

Tumor necrosis factor alpha

tr-KIT:

Truncated KIT

VAD:

Vitamin A deficient

WNT5a:

Wnt family member 5A

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Mäkelä, JA., Toppari, J. (2017). Spermatogenesis. In: Simoni, M., Huhtaniemi, I. (eds) Endocrinology of the Testis and Male Reproduction. Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-44441-3_13

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