Source: Pixabay/TBIT

News • Histones & protamines

Infertility's roots may lie in our DNA

Pathological infertility is a condition affecting roughly 7% of human males, and among those afflicted, 10-15% are thought to have a genetic cause. However, pinpointing the precise genes responsible for the condition has been difficult, due to the extensive number involved in generating and developing sperm cells.

In a new paper appearing in Science Signaling, a Japanese team reports unravelling the mechanism behind one cause of infertility - incomplete development of the proteins packaging DNA in sperm cells - and further, success in making test mice fertile by replacing a single amino acid on a key protein. In every cell, thread-like DNA is wound tightly in the nucleus around bobbin-like proteins called 'histones'. And in sperm cells - the smallest humans produce - another protein called 'protamine' is needed to wind the strands even tighter. "It's been known for about 30 years that protamines are modified and matured during sperm development to enable proper functioning," explains first author Katsuhiko Itoh from Kyoto University's Graduate School of Medicine. "This prompted us to disclose the underlying mechanism and biological consequences of protamine regulation, so that we can see how this process contributes to 'spermatogenesis' - the making sperm cells."

Dephosphorylation of Protamine 2 at serine 56 is key in proper DNA packaging in...
Dephosphorylation of Protamine 2 at serine 56 is key in proper DNA packaging in developing sperm cells. However, dysfunction in Hspa4l results in Ppp1cc2 not dephosporylating Protamine 2

Source: Kyoto University/Itoh Lab

The team focused on a series of chaperones: proteins that assist in processing other proteins. Detailed genetic analysis revealed that a chaperone known as Hspa4l is key to proper sperm cell development, and that its dysfunction has consequences similar to deficiency in a gene called Ppp1cc2. "Further study showed that Hspa4l is vital for the proper functioning of phosphatase Ppp1cc2, a protein regulator," continues Itoh. "A dysfunction in Hspa41 stops Ppp1cc2 from reaching chromatin, resulting in failure to dephosphrylate protamine 2 at serine 56, and with protamine 2 not functioning, sperm cells don't develop."

With these data, the team produced a mouse in which serine 56 was substituted to alanine, dephosphomimetic of dephosphorylated serine: the single amino acid replacement that made all the difference. When combined with a mutation resulting in non-functioning Hspa41, the mouse showed no dysfunction in spermatogenesis, effectively preserving fertility.

Itoh emphasizes that his team's research shows the value in studying protamine modification in the process of sperm cell maturation. The group hopes to further unravel the complex network of gene interaction and protein modification in spermatogenesis, and its further implications for infertility.


Source: Kyoto University

02.04.2019

Read all latest stories

Related articles

Photo

News • Relapse rate research

Breast cancer: Fertility preservation measures do not increase recurrence risk

A new study shows that women with a breast cancer diagnosis undergoing procedures for fertility preservation are not at increased risk of recurrence of the disease or disease-specific mortality.

Photo

News • Genetics research

Chromosomes: How the 'extra X factor' is putting men at risk

Around one in 500 men could be carrying an extra X or Y chromosome – most of them unaware – putting them at increased risk of diseases such as type 2 diabetes, atherosclerosis and thrombosis.

Photo

News • Oral contraceptives

Can birth control pills keep you from recognising emotions?

The pill could be blurring your social judgement ‒ but perhaps not enough so you'd notice. By challenging women to identify complex emotional expressions like pride or contempt, rather than basic…

Related products

Sarstedt – Low DNA Binding Micro Tubes

Research Use Only

Sarstedt – Low DNA Binding Micro Tubes

SARSTEDT AG & CO. KG
MolGen - Extraction Kit

Extraction

MolGen - Extraction Kit

MolGen
MolGen - MoaA kit

Amplification/Detection

MolGen - MoaA kit

MolGen
MolGen - PurePrep 24D

Extraction

MolGen - PurePrep 24D

MolGen
MolGen – PurePrep 96

Extraction

MolGen – PurePrep 96

MolGen
Subscribe to Newsletter